methadone

Research Excerpts

Overview

Methadone (MTD) is a commonly prescribed treatment for opioid use disorder in pregnancy, despite limited information on the effects of passive exposure on fetal brain development. Methadone is a centrally-acting synthetic opioid analgesic widely used in methadone maintenance therapy (MMT) programs throughout the world.

Excerpt	Reference	Relevance
"Methadone is a μ-opioid receptor agonist widely used in the treatment of narcotic addiction and chronic pain conditions. "	( Mechanism-based inactivation of cytochrome P450 2B6 by methadone through destruction of prosthetic heme. Amunugama, HT; Hollenberg, PF; Zhang, H, 2012)	2.07
"Methadone is a synthetic opioid used for the maintenance treatment (MMT) of heroin dependence. "	( Association of the D-amino acid oxidase gene with methadone dose in heroin dependent patients under methadone maintenance treatment. Chen, ACH; Chung, RH; Fang, CP; Kuo, HW; Liu, SC; Liu, TH; Liu, YL; Tsou, HH; Wang, SC, 2022)	2.42
"Methadone is a highly effective treatment for opioid use disorder. "	( Methadone exposures reported to poison control centers in the United States following the COVID-19-related loosening of federal methadone regulations. Doyon, S; Hart, K; Welsh, C, 2022)	3.61
"Methadone is a long-acting analgesic that targets the N-methyl-D-aspartate (NMDA) receptor in addition to the mu opioid receptor and has benefit in adult burn patients."	( Intraoperative Methadone Use in Pediatric Burn Patients. Ambardekar, A; Carlson, A; Iskander, I; Pham, D; Price, C; Reisch, J, 2022)	1.8
"Methadone is a synthetic opioid mostly used for detoxification therapy, as its use increases; the possibility for methadone-induced cardiotoxicity may rise. "	( Is high sensitive-troponin I a reliable biomarker for cardiac injury in methadone toxicity? A prospective cross-sectional study. Dehkordi, AD; Gheshlaghi, F; Sadeghi, M; Shemirani, H, 2022)	2.4
"Methadone is a recommended medication for opioid agonist maintenance therapy (OAMT). "	( Assessing cardiac safety among clients receiving methadone as part of opioid agonist maintenance therapy (OAMT) in Durban, South Africa. Marks, M; Naidoo, DP; Prakaschandra, DR; Scheibe, A, )	1.83
"Methadone (MTD) is a commonly prescribed treatment for opioid use disorder in pregnancy, despite limited information on the effects of passive exposure on fetal brain development. "	( Perinatal methadone exposure attenuates myelination and induces oligodendrocyte apoptosis in neonatal rat brain. Cai, J; Chu, T; Devlin Phinney, LA; Gibson, JM; Kong, M; Mellen, N; Wethall, AC; Zeng, W, 2022)	2.57
"Methadone is a centrally-acting synthetic opioid analgesic widely used in methadone maintenance therapy (MMT) programs throughout the world. "	( Chronic exposure to methadone impairs memory, induces microgliosis, astrogliosis and neuroinflammation in the hippocampus of adult male rats. Abdollahifar, MA; Aliaghaei, A; Boroujeni, ME; Fathabadi, FF; Fathi, M; Moghaddam, MH; Navaei, F; Norouzian, M; Vakili, K; Zamani, N, 2022)	2.49
"Methadone is a synthetic μ-opioid receptor agonist used for cancer or non-cancer pain and the treatment of opioid dependence."	( Methadone-induced hypoglycemia: A case report. Hatami, N; Maghsoomi, Z; Malboosbaf, R, 2023)	3.07
"Methadone is a centrally-acting synthetic opioid analgesic widely used in the methadone maintenance therapy (MMT) programs throughout the world. "	( Chronic exposure to methadone induces activated microglia and astrocyte and cell death in the cerebellum of adult male rats. Aliaghaei, A; Hassanian-Moghaddam, H; Osgoei, LT; Zamani, N, 2023)	2.68
"Methadone is an effective, safe, and cost-saving treatment for patients with refractory cancer pain."	( Methadone switching for refractory cancer pain. Ding, H; Fang, L; Gong, L; He, C; Song, Y; Sun, J; Xin, W; Zhong, L; Zhou, Q, 2022)	3.61
"Methadone is an opioid used in treating chronic and acute pains as well as opioid dependence. "	( Punica granatum Seed Essential Oil Suppressed Methadone-Induced Cell Death by Natural Antioxidant Activity. Khoshkhoy, S; Mahdizadeh, H; Zhaleh, H, 2023)	2.61
"Methadone is an effective analgesic with unique pharmacokinetic and pharmacodynamic variables. "	( Comparing National Methadone Equianalgesic Tools. Atayee, RS; Edmonds, KP; Wen, RY, 2023)	2.68
"Oral methadone is a feasible alternative to IV methadone for patients undergoing spine surgery regarding both pain scores and postoperative opioid consumption."	( Comparison of oral versus intravenous methadone on postoperative pain and opioid use after adult spinal deformity surgery: A retrospective, non-inferiority analysis. Dunn, LK; Esfahani, K; Naik, BI; Tennant, W; Tsang, S, 2023)	1.7
"Methadone is a complex but useful medication for pain management in palliative care. "	( Comparing Methadone Rotation to Consensus Opinion. Quirk, KC; Rodgers, PE; Saul, DC; Silveira, MJ; Smith, MA, 2020)	2.4
"Methadone maintenance is an effective treatment for opioid use disorder (OUD), yet many methadone-maintained patients (MMPs) struggle with cocaine use during OUD recovery. "	( Increased neural activity in the right dorsolateral prefrontal cortex during a risky decision-making task is associated with cocaine use in methadone-maintained patients. Ayaz, H; Brooner, RK; Dunn, KE; Huhn, AS; Sweeney, MM; Yip, SW, 2019)	2.16
"Methadone is a long-acting opioid receptor agonist. "	( Methadone associated long term hearing loss and nephrotoxicity; a case report and literature review. Brent, J; Ghasemi, S; Izadpanahi, S; Mehrpour, O; Yaghoubi, MA, 2019)	3.4
"Methadone is a potent opioid exerting an analgesic effect through N-methyl-D-aspartate receptor antagonism and the inhibition of serotonin and noradrenaline reuptake. "	( Intraoperative Methadone Reduces Pain and Opioid Consumption in Acute Postoperative Pain: A Systematic Review and Meta-analysis. Ashmawi, HA; de Orange, FA; Machado, FC; Vieira, JE, 2019)	2.31
"Methadone is an opioid commonly used for acute pain management in burn patients. "	( Risk Factors and Prevalence of QTc Prolongation in Adult Burn Patients Receiving Methadone. Boyd, AN; Hartman, BC; Hester, AM; Schoenle, MK; Sood, R; Walroth, TA, 2020)	2.23
"Methadone continues to be an important medication for the treatment of paediatric and adult cancer-related pain. "	( Emerging Challenges to the Safe and Effective Use of Methadone for Cancer-Related Pain in Paediatric and Adult Patient Populations. Ajayi, TA; Atayee, RS; Edmonds, KP; Saunders, IM; Willeford, A, 2020)	2.25
"Methadone is an opioid analgesic commonly prescribed for pharmacologic management of NAS."	( Utilizing Pediatric Physiologically Based Pharmacokinetic Models to Examine Factors That Contribute to Methadone Pharmacokinetic Variability in Neonatal Abstinence Syndrome Patients. Akinbi, H; Butler, D; Emoto, C; Fukuda, T; McPhail, BT; Vinks, AA; Wiles, JR, 2020)	1.49
"Methadone is a medication-assisted treatment used to treat opioid dependence and chronic pain."	( The effect of methadone on the hypothalamic pituitary gonadal axis and sexual function: A systematic review. Ortman, HA; Siegel, JA, 2020)	1.64
"Methadone is a long-acting opioid that has been reported to reduce postoperative pain scores and analgesic requirements and may attenuate development of chronic postsurgical pain. "	( Postoperative Pain and Analgesic Requirements in the First Year after Intraoperative Methadone for Complex Spine and Cardiac Surgery. Avram, MJ; Benson, J; Bilimoria, S; Deshur, MA; Dickerson, D; Greenberg, SB; Maher, CE; Murphy, GS; Shear, TD; Szokol, JW; Teister, KJ; Trenk, GJ, 2020)	2.22
"Methadone is a useful option in the treatment of cancer pain. "	( Methadone rotation for cancer pain: an observational study. Hum, A; Tan, C; Wong, JF; Yee, CM, 2022)	3.61
"Methadone appears to be a promising candidate for pain management. "	( Investigation of binary and ternary solvent systems for dermal delivery of methadone. Hadgraft, J; Kung, CP; Lane, ME; McCulloch, R; Patel, B; Sil, BC; Zhang, Y, 2020)	2.23
"Methadone is a synthetic opioid used as maintenance treatment for patients addicted to heroin. "	( Genetic variants in NECTIN4 encoding an adhesion molecule are associated with continued opioid use. Chen, ACH; Chung, RH; Fang, CP; Kuo, HW; Liu, CC; Liu, SC; Liu, TH; Liu, YL; Tsou, HH; Wang, SC, 2020)	2
"Methadone is a synthetic opioid agonist with notoriously unique properties, such as lower abuse liability and induced relief of withdrawal symptoms and drug cravings, despite acting on the same opioid receptors triggered by classic opioids-in particular the "	( Atomic-Level Characterization of the Methadone-Stabilized Active Conformation of Filizola, M; Kapoor, A; Provasi, D, 2020)	2.27
"Methadone is an effective method of preventing and treating iatrogenic opioid withdrawal; however, it carries an Food and Drug Administration Boxed Warning due to the potential to prolong the corrected QT interval and potentially lead to life-threatening arrhythmias."	( Methadone's Effect on Cardiac Repolarization: Safety in the PICU. Friedman, SD; Kovach, JR; Thompson, NE, 2020)	2.72
"Methadone is an opioid with several desirable pharmacological features, including a long elimination half-life. "	( [Intraoperative methadone for post-operative pain]. Brix, LD; Friesgaard, KD; Møller, JF; Nikolajsen, L; Uhrbrand, CG, 2020)	2.35
"Methadone is an analgesic drug used for pain treatment and heroin substitution. "	( Cytotoxic and Senolytic Effects of Methadone in Combination with Temozolomide in Glioblastoma Cells. Beltzig, L; Haas, B; Kaina, B; Piee-Staffa, A, 2020)	2.28
"Methadone is an opioid that often leads to fatalities. "	( Brain/blood ratios of methadone and ABCB1 polymorphisms in methadone-related deaths. Andresen-Streichert, H; Beer-Sandner, B; Erb, R; Hischke, S; Iwersen-Bergmann, S; Jungen, H; Müller, A; Plattner, S, 2021)	2.38
"Methadone is a synthetic opioid, a pure agonist of the μ receptor. "	( Forensic pathological study of methadone-related deaths in the Genoa (Italy) district: A six-year study. Barranco, R; Bedocchi, D; Bonsignore, A; Drommi, M; Errico, S; Ventura, F, 2021)	2.35
"Methadone is an opioid drug commonly prescribed for treating opioid use disorder in pregnant women and was found to accumulate at high levels in the fetal brain of mice, which fell quickly after birth."	( Prenatal methadone exposure disrupts behavioral development and alters motor neuron intrinsic properties and local circuitry. Allen, MR; Atwood, BK; Baucum, AJ; Engleman, EA; Gao, Y; Grecco, GG; Haggerty, DL; Hoffman, H; Huang, JY; Katner, SN; Kim, J; Lu, HC; Masters, AR; Metzger, CE; Mork, BE; Morris, CW; Newell, EA; Reeves, KC; Sheets, PL; Wu, YC; Yamamoto, BK, 2021)	1.76
"Methadone is a low-cost, strong opioid that is increasingly used as a first-line treatment for pain in palliative care (PC). "	( First-line methadone for cancer pain: titration time analysis. Armesto, A; Bertolino, M; Bruera, E; Bunge, S; Dran, G; Mammana, G; Orellana, F; Peirano, G; Vega, F, 2021)	2.45
"Methadone is an evidence-based treatment for opioid use disorder (OUD) and pain management. "	( Pronounced Regional Disparities in United States Methadone Distribution. Furst, JA; McCall, KL; Mynarski, NJ; Piper, BJ, 2022)	2.42
"Methadone (MTD) is a synthetic analgesic drug used for treating opioid dependence and effectively used clinically for patients with severe pain. "	( Review of LC techniques for determination of methadone and its metabolite in the biological samples. Shan, X; Yang, B; Zhang, L, 2021)	2.32
"Methadone is an effective medication for treating pain and has unique characteristics that require specialized knowledge to prescribe safely. "	( Methadone for Palliative Care Providers: A Case-Based Flipped Classroom Module for Faculty and Fellows. Biewald, MA; Lindenberger, E; Scarborough, B, 2021)	3.51
"Methadone is a synthetic opioid used as an analgesic and for the treatment of opioid abuse disorder. "	( Pharmacokinetic modeling of R and S-Methadone and their metabolites to study the effects of various covariates in post-operative children. Aruldhas, BW; Gao, H; Heathman, MA; Ly, RC; Masters, AR; Overholser, BR; Packiasabapathy, S; Quinney, SK; Sadhasivam, S, 2021)	2.34
"Methadone is an opioid prescribed for pain management and is also provided through opioid treatment programs to treat opioid use disorders."	( Methadone Prescribing and Overdose and the Association with Medicaid Preferred Drug List Policies - United States, 2007-2014. Alexander, C; Bohm, M; Faul, M, 2017)	2.62
"Methadone is a widely used opioid agonist treatment associated with QT prolongation and torsades de pointes. "	( QT interval prolongation in opioid agonist treatment: analysis of continuous 12-lead electrocardiogram recordings. Brown, AL; Calver, L; Dunlop, AJ; Gill, A; Isbister, GK; Scott, AJ, 2017)	1.9
"Methadone is a valid option, but its safety profile is not completely known."	( Neonatal Abstinence Syndrome: Update on Diagnostic and Therapeutic Strategies. Agosti, M; Allegaert, K; Cavallaro, G; Fumagalli, M; Mosca, F; Raffaeli, G; Tibboel, D; Wildschut, ED, 2017)	1.18
"Methadone is a synthetic μ-opioid receptor agonist that is used in the management of pain, neonatal abstinence withdrawal syndrome, and opioid dependence. "	( A case report of methadone-associated hypoglycemia in an 11-month-old male. Breault, DT; Burns, MM; Stefater, MA; Toce, MS, 2018)	2.26
"Methadone is a potent analgesic used to treat refractory cancer pain. "	( Can Saliva and Plasma Methadone Concentrations Be Used for Enantioselective Pharmacokinetic and Pharmacodynamic Studies in Patients With Advanced Cancer? George, R; Good, P; Hardy, J; Haywood, A; Hennig, S; Khan, S; Norris, R, 2017)	2.21
"Methadone is a standard treatment for opioid dependence in pregnancy; however, its impact on maternal corrected QT interval (QTc) has not been evaluated. "	( Corrected QT Interval and Methadone Dose and Concentrations in Pregnant and Postpartum Women. Bogen, DL; Hanusa, BH; Mendelson, MA; Perel, JM; Sherman, F; Wisner, KL, )	1.87
"Methadone is a synthetic, long-acting opioid with a single chiral center forming two enantiomers, (R)-methadone and (S)-methadone, each having specific pharmacological actions. "	( Effects of cytochrome P450 single nucleotide polymorphisms on methadone metabolism and pharmacodynamics. Ahmad, T; Rankin, GO; Valentovic, MA, 2018)	2.16
"Methadone is an opioid that is only approved for replacement therapy in Austria."	( Methadone as anticancer treatment: hype, hope, or hazard? : A series of case reports and a short review of the current literature and recommendations of the societies. Hackner, K; Kreye, G; Masel, EK; Nauck, F; Stich, B, 2018)	2.64
"Methadone is a CYP450 substrate with altered pharmacokinetics during pregnancy."	( The Use of Serum Methadone/Metabolite Ratios to Monitor Changing Perinatal Pharmacokinetics. Fassbender, C; Graas, J; Leamon, MH; McCarthy, JJ; Vasti, EJ; Ward, C, )	1.19
"Methadone is an attractive medication for treating children with advanced cancer with pain as it is the only long-acting opioid available as a liquid. "	( Methadone as the Initial Long-Acting Opioid in Children with Advanced Cancer. Bruera, E; Dibaj, S; Liu, D; Madden, K; Mills, S; Williams, JL, 2018)	3.37
"Methadone is a valuable opioid in the management of patients who have cancer with pain. "	( Methadone: Maximizing Safety and Efficacy for Pain Control in Patients with Cancer. Costantino, RC; McPherson, AL; McPherson, ML, 2018)	3.37
"Methadone is a long-acting opioid receptor agonist. "	( The impact of OPRM1's genetic polymorphisms on methadone maintenance treatment in opioid addicts: a systematic review. Ghachem, R; Moula, O; Oueslati, B, 2018)	2.18
"Methadone is an opioid analgesic in veterinary and human medicine. "	( The construction and application of a population physiologically based pharmacokinetic model for methadone in Beagles and Greyhounds. Elwell-Cuddy, T; KuKanich, B; Li, M; Lin, Z, 2018)	2.14
"Methadone is a synthetic opioid with unique pharmacodynamic and pharmacokinetic properties. "	( Methadone for Pain Management in Children with Cancer. Anghelescu, DL; Habashy, C; Hall, EA; Springer, E, 2018)	3.37
"Methadone is known to be a risk factor for sudden death by enlarging ECG QT corrected (QTc) interval. "	( QT length during methadone maintenance treatment: gene × dose interaction. Bellivier, F; Bloch, V; Laplanche, JL; Lepine, JP; Marees, AT; Marie-Claire, C; Mouly, S; Naccache, F; Prince, N; Vorspan, F; Zerdazi, EH, 2019)	2.3
"Methadone maintenance is an effective treatment for opioid use disorder, yet many methadone-maintained patients (MMPs) continue to struggle with chronic relapse. "	( Prefrontal cortex response to drug cues, craving, and current depressive symptoms are associated with treatment outcomes in methadone-maintained patients. Ayaz, H; Brooner, RK; Dunn, KE; Huhn, AS; Kidorf, MS; Sweeney, MM; Tompkins, DA, 2019)	2.16
"Methadone is a long-acting opioid known for its unique pharmacokinetic and pharmacodynamic properties. "	( Attitudes, Beliefs, and Practices of Pediatric Palliative Care Physicians Regarding the Use of Methadone in Children With Advanced Cancer. Bruera, E; Liu, D; Madden, K, 2019)	2.18
"Methadone is a long-acting synthetic opioid with antagonist properties at the n-methyl-d-aspartate (NMDA) receptor."	( Role of Methadone in Extracorporeal Membrane Oxygenation: Two Case Reports. Arabia, FA; Chan, A; Chung, JS; D'Attellis, N; Dong, E; Fellin, R; Ng, D; Nurok, M; Ramzy, D, 2018)	1.64
"Methadone is a long-acting mu-opioid receptor agonist that has been shown to increase retention in treatment programs and attendance at prenatal care while decreasing pregnancy complications."	( Pharmacological treatment of opioid use disorder in pregnancy. Klie, KA; Rodriguez, CE, 2019)	1.24
"Methadone is a synthetic opioid used to treat opiate withdrawal and addiction. "	( Methadone's effects on pentylenetetrazole-induced seizure threshold in mice: NMDA/opioid receptors and nitric oxide signaling. Aghaei, I; Bahramnejad, E; Dehpour, AR; Kazemi Roodsari, S; Rahimi, N, 2019)	3.4
"Methadone is a synthetic mu-opioid receptor agonist used in the treatment of chronic pain and opioid dependence. "	( Opioid Toxidrome Following Grapefruit Juice Consumption in the Setting of Methadone Maintenance. Cruz, MD; Ershad, M; Greenberg, MI; Mckeever, R; Mostafa, A; Vearrier, D, )	1.8
"Methadone is a vital treatment for women with opioid use disorder in pregnancy. "	( Methadone, Pierre Robin sequence and other congenital anomalies: case-control study. Addor, MC; Barisic, I; Cleary, B; de Walle, HEK; Dolk, H; Gatt, M; Klungsoyr, K; Loane, M; Matias Dias, C; McDonnell, B; Neville, A; Pierini, A; Rissmann, A; Tucker, DF; Zurriaga, O, 2020)	3.44
"Methadone is a widely used substitution therapy for opioid addiction. "	( Functional impact of ABCB1 variants on interactions between P-glycoprotein and methadone. Chiou, MH; Hsieh, YW; Huang, CL; Hung, CC; Lane, HY; Teng, YN, 2013)	2.06
"Methadone is an atypical opioid that inhibits hyperalgesia through NMDA-blockade, especially at low doses."	( The use of very-low-dose methadone for palliative pain control and the prevention of opioid hyperalgesia. Bruera, E; Buckley, JS; Salpeter, SR, 2013)	1.41
"Methadone is a commonly used opioid in hospice and palliative care for patients with refractory pain. "	( Dose ratios between high dose oral morphine or equivalents and oral methadone. Chatham, MS; Dodds Ashley, ES; Juba, KM; Svengsouk, JS, 2013)	2.07
"Methadone is a well-studied, safe, and effective medication when dispensed and consumed properly. "	( Safe methadone induction and stabilization: report of an expert panel. Baxter, LE; Campbell, A; Deshields, M; Levounis, P; Martin, JA; McNicholas, L; Payte, JT; Salsitz, EA; Taylor, T; Wilford, BB, )	2.09
"Methadone is a synthetic opioid that binds to the κ-opioid receptor with a low affinity. "	( The association of genetic polymorphisms in the κ-opioid receptor 1 gene with body weight, alcohol use, and withdrawal symptoms in patients with methadone maintenance. Chang, YS; Chen, AC; Chen, CH; Chung, RH; Fang, CP; Ho, IK; Hsiao, CF; Huang, BH; Kuo, HW; Lin, KM; Liu, SC; Liu, YL; Shih, YH; Tsou, HH; Wang, SC; Wu, HY, 2014)	2.05
"Methadone is a synthetic opioid which is being used with increased frequency in the palliative care setting for management of complex pain. "	( Methadone and oedema in the palliative care setting: a case report and review of the literature. Buchanan, D; Dawson, C; McFatter, F; Paterson, F, 2014)	3.29
"Methadone is a useful analgesic for neuropathic and nociceptive pain. "	( Effectiveness of the buccal mucosa route for methadone administration at the end of life. Spaner, D, 2014)	2.1
"Methadone is an effective adjuvant to LA and was recently reported to inhibit cardiac Na(+) channels."	( Methadone is a local anaesthetic-like inhibitor of neuronal Na+ channels and blocks excitability of mouse peripheral nerves. Ahrens, J; Doll, T; Foadi, N; Kistner, K; Leffler, A; Schulze, V; Stoetzer, C; Stüber, T; Wegner, F; Wirths, M, 2015)	2.58
"Methadone is a potent opioid agonist widely used in opioid maintenance therapy. "	( Role of Methadone in Induction and/or Exacerbation of Cluster Headache in Patients Treated for Opioid Addiction. Diot, C; Donnadieu-Rigole, H; Eiden, C; Leglise, Y; Peyrière, H, )	2.01
"Methadone is a long-acting opioid with considerable unexplained interindividual variability in clearance. "	( Differences in Methadone Metabolism by CYP2B6 Variants. Friedel, C; Gadel, S; Kharasch, ED, 2015)	2.21
"Methadone is an effective treatment for opioid dependence. "	( Methadone continuation versus forced withdrawal on incarceration in a combined US prison and jail: a randomised, open-label trial. Clarke, J; Larney, S; McKenzie, M; Noska, A; Reddy, M; Rich, JD; Tran, L; Wong, JB; Zaller, N, 2015)	3.3
"Methadone is a long-acting opioid agonist that is frequently prescribed as a treatment for opioid addiction. "	( Methadone's effect on nAChRs--a link between methadone use and smoking? Salminen, O; Talka, R; Tuominen, RK, 2015)	3.3
"Methadone is an important drug in the management of both cancer-related and non-cancer-related pain and is the main pharmacologic agent used in the treatment of opioid addiction. "	( Methadone Use and the Risk of Hypoglycemia for Inpatients With Cancer Pain. Flory, JH; Koranteng, L; Moryl, N; Thaler, HT; Wiesenthal, AC, 2016)	3.32
"Methadone is a long-acting opioid that carries a higher risk profile than other opioids. "	( Methadone related deaths compared to all prescription related deaths. Castillo, EM; Egnatios, J; Lee, A; Lee, O; Lev, R; Lucas, J; Petro, S; Vilke, GM, 2015)	3.3
"Methadone is a Schedule II drug best known for its use in the treatment of opioid dependence. "	( Methadone Maintenance Therapy and the Dental Patient. Maloney, W; Raymond, G, )	3.02
"Methadone is an opioid with unique pharmacological properties, which render it clinically distinct from other opioids."	( Opioid rotation: A case example using methadone in spinal cord injury. Pawasauskas, J, )	1.12
"Methadone is a potent lipophilic synthetic opioid that is effective in the treatment of cancer pain and perceived benefit in difficult pain control scenarios (especially in cases of neuropathic pain). "	( Quantitative determination of the enantiomers of methadone in human plasma and saliva by chiral column chromatography coupled with mass spectrometric detection. George, R; Good, P; Hardy, J; Haywood, A; Hennig, S; Khan, S; Lobb, M; Norris, R, 2016)	2.13
"Methadone maintenance is an effective treatment for opioid dependence but is rarely initiated in US jails. "	( Interim methadone and patient navigation in jail: Rationale and design of a randomized clinical trial. Dunlap, L; Jaffe, JH; Kelly, SM; Mitchell, SG; O'Grady, KE; Schwartz, RP; Sharma, A; Zarkin, GA, 2016)	2.31
"Methadone is a substrate of the permeability glycoprotein (P-gp) efflux transporter, which is encoded by the ABCB1 (MDR1) gene. "	( Relationship between ABCB1 polymorphisms and serum methadone concentration in patients undergoing methadone maintenance therapy (MMT). Ibrahim, MA; Ismail, R; Lee, CS; Lee, YY; Mohamad, N; Mohd Yasin, MA; Musa, N; Tan, SC; Zahari, Z, 2016)	2.13
"Methadone is a μ-opioid agonist widely used for the treatment of pain, and for detoxification or maintenance treatment in opioid addiction. "	( Population Genetic-Based Pharmacokinetic Modeling of Methadone and its Relationship with the QTc Interval in Opioid-Dependent Patients. Crettol, S; Csajka, C; Eap, CB; Guidi, M, 2016)	2.13
"Methadone is a synthetic opioid analgesic with potential advantages over other commonly used opioids. "	( Methadone analgesia in the critically ill. Elefritz, JL; Lyaker, MR; Murphy, CV; Papadimos, TJ, 2016)	3.32
"Methadone is a unique µ-opioid receptor agonist. "	( Characterization of methadone as a β-arrestin-biased μ-opioid receptor agonist. Arima, T; Doi, S; Mori, T; Narita, M; Suzuki, T; Takahashi, T; Uchida, M; Uezono, Y; Uzawa, N; Yawata, A, 2016)	2.2
"Methadone is a full μ-opioid receptor agonist used in the treatment of heroin addiction. "	( Metabolomics of methadone: clinical and forensic toxicological implications and variability of dose response. Dinis-Oliveira, RJ, 2016)	2.22
"Methadone maintenance is a standard treatment for opiate-dependent individuals. "	( Hot and cold executive functions in pure opioid users undergoing methadone maintenance treatment: Effects of methadone dose, treatment duration, and time between last methadone administration and testing. Barahmand, U; Khazaee, A; Mohammadi, K; Tavakolian, E, )	1.81
"Methadone is an effective and sustainable second-line alternative opioid for the treatment of cancer-related pain. "	( Efficacy and Safety of Two Methadone Titration Methods for the Treatment of Cancer-Related Pain: The EQUIMETH2 Trial (Methadone for Cancer-Related Pain). Berleur, MP; Chvetzoff, G; Derniaux, A; Filbet, M; Lefebvre, D; Lefki, S; Poulain, P; Serra, E; Tremellat, F, 2016)	2.17
"Methadone is an opioid analgesic that is effective in the treatment of neuropathic pain, is excreted by the bowels, is highly lipophilic, and can be administered through the oral, buccal, or sublingual routes."	( Use of Methadone as an Adjuvant Medication to Low-Dose Opioids for Neuropathic Pain in the Frail Elderly: A Case Series. Grief, CJ; Grossman, D; Kirstein, A; Pan, J; Vu Bach, T, 2016)	1.61
"Methadone is a synthetic opioid that presents some challenges in dose titration and is recognised to cause potentially fatal arrhythmias in some patients."	( Methadone for cancer pain. Derry, S; Nicholson, AB; Watson, GR; Wiffen, PJ, 2017)	2.62
"Methadone is a cornerstone therapy for opioid addiction and a public health strategy for HIV/AIDS and hepatitis C reduction. "	( Current Concepts in Methadone Metabolism and Transport. Kharasch, ED, 2017)	2.22
"Methadone (ME) is a highly effective opioid agonist used for difficult pain syndromes. "	( Switching from methadone to a different opioid: what is the equianalgesic dose ratio? Bruera, E; Hanohano, J; Kaur, G; Munsell, M; Palla, S; Pei, BL; Walker, PW; Zhang, K, 2008)	2.14
"Methadone is a synthetic opioid, an analgesic and an antiaddictive. "	( The effects of chiral isolates of methadone on the cardiac potassium channel IKr. Lin, C; Molnar, J; Somberg, J; Somberg, T, 2009)	2.07
"Methadone is an excellent choice for pain in frail older adults."	( Methadone: an effective, safe drug of first choice for pain management in frail older adults. Gallagher, R, 2009)	3.24
"Methadone is a drug of choice in the treatment of a withdrawal (Grade B, LOE 2)."	( [Recommendations for analgesia and sedation in neonatal intensive care]. Rawicz, M, )	0.85
"Methadone is a long-acting synthetic opioid with high affinity for various opioid receptors, especially for m-opioid receptors. "	( [Methadone treatment and its dangers]. Jodziūniene, L; Lazauskas, R; Reingardiene, D, 2009)	2.71
"Methadone is an opioid analgesic of step 3 of the World Health Organization (WHO) analgesic ladder."	( The role of methadone in cancer pain treatment--a review. Leppert, W, 2009)	2.17
"Methadone is an important opioid analgesic at step 3 of the WHO analgesic ladder. "	( The role of methadone in cancer pain treatment--a review. Leppert, W, 2009)	2.17
"Methadone is an effective therapy for heroin addiction, but the public health benefits are compromised by diversion and injection of prescribed methadone. "	( The acceptability, safety, and tolerability of methadone/naloxone in a 50:1 ratio. Bell, J; Graham, R; Korompay, K; Rizzo, S; Ryan, A; Shearer, J; Sindhusake, D; Somogyi, AA, 2009)	2.05
"Methadone is an effective maintenance therapy intervention for the treatment of heroin dependence as it retains patients in treatment and decreases heroin use better than treatments that do not utilise opioid replacement therapy. "	( Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Breen, C; Davoli, M; Kimber, J; Mattick, RP, 2009)	3.24
"Methadone is a proven first-line treatment in opioid dependence but few studies have addressed the efficacy of different isoforms of methadone or the transfer from one form to the other. "	( Feasability and safety of transfer from racemic methadone to (R)-methadone in primary care: clinical results from an open study. Soyka, M; Zingg, C, 2009)	2.05
"Methadone hydrochloride is a synthetic mu-opioid receptor agonist with potent analgesic properties. "	( Pharmacokinetics of the injectable formulation of methadone hydrochloride administered orally in horses. Barker, SA; Hosgood, G; Linardi, RL; Natalini, CC; Short, C; Stokes, AM, 2009)	2.05
"Methadone is an opioid agonist often given to manage acute and chronic pain. "	( Acute methadone treatment reduces myocardial infarct size via the delta-opioid receptor in rats during reperfusion. Gross, ER; Gross, GJ; Hsu, AK, 2009)	2.28
"Methadone is an effective and inexpensive opioid for cancer pain treatment. "	( Methadone initiation and rotation in the outpatient setting for patients with cancer pain. Bruera, E; Calderon, B; de la Cruz, M; El Osta, B; Li, Z; Palmer, JL; Parsons, HA, 2010)	3.25
"Methadone is a synthetic opioid used to relieve pain, treat opioid withdrawal, and wean heroin addicts. "	( Gas chromatography-mass spectrometry method for the determination of methadone and 2-ethylidene-1,5-dimethyl-3, 3-diphenylpyrrolidine (EDDP). Bjergum, MW; Langman, LJ; Snozek, CL, 2010)	2.04
"Methadone is a medication valued for its effectiveness in the treatment of heroin addiction; however, many fatal poisonings associated with its use have been reported over the years. "	( OPRM1 and CYP2B6 gene variants as risk factors in methadone-related deaths. Bunten, H; Liang, WJ; Osselton, D; Pounder, DJ; Seneviratne, C, 2010)	2.06
"Methadone is a widely used therapeutic opioid in narcotic addiction and neuropathic pain syndromes. "	( Methadone induces necrotic-like cell death in SH-SY5Y cells by an impairment of mitochondrial ATP synthesis. Aguirre, N; Bednarczyk, P; Cuenca-Lopez, MD; de Mera, RM; Galindo, MF; Jordán, J; Karachitos, A; Kmita, H; Perez-Alvarez, S; Puerta, E, 2010)	3.25
"Methadone treatment is a well-recognised cause of QT interval lengthening in adults."	( Maternal methadone therapy increases QTc interval in newborn infants. Bhoyar, A; Ewer, AK; Holder, G; Hussain, T; Parikh, R, 2011)	1.51
"Methadone (Mtd) is a widely used opioid drug associated with the side effect of hyperprolactinemia. "	( Inhibitory action of methadone and its metabolites on erg-mediated K+ current in GH₃ pituitary tumor cells. Chen, BS; Chen, CT; Hsu, TI; Huang, MH; Kang, YF; Shen, AY; Wang, TS; Wu, HM; Wu, SN, 2011)	2.13
"Methadone is an opioid analgesic that is also commonly used to prevent opioid-withdrawal symptoms in patients undergoing treatment for opioid addiction. "	( Methadone: marvelous, malevolent, or merely misunderstood? Martin, CM, 2011)	3.25
"Methadone is a prescription drug used to help individuals overcome withdraws from highly addictive illicit substances, such as heroin, but it has detrimental oral health effects. "	( Methadone and oral health--a brief review. Brondani, M; Park, PE, 2011)	3.25
"Methadone is a synthetic opioid primarily metabolized by CYP3A4 and, to a lesser degree, by other isoenzymes, including CYP1A2."	( Methadone toxicity due to smoking cessation--a case report on the drug-drug interaction involving cytochrome P450 isoenzyme 1A2. Kolluru, S; Molina, C; Nguyen, T; Speake, J; Wahawisan, J, 2011)	2.53
"Methadone is a racemic compound composed of the R-form and S-form enantiomers. "	( CYP2B6 polymorphisms influence the plasma concentration and clearance of the methadone S-enantiomer. Chan, HW; Chen, CH; Chen, CY; Ho, IK; Hsiao, CF; Huang, CL; Lin, KM; Lin, L; Lin, PS; Liu, ML; Liu, SC; Liu, YL; Su, LW; Tan, HK; Tian, JN; Tsai, MH; Tsou, HH; Wang, SC; Wu, CS; Wu, HY; Yang, YH, 2011)	2.04
"Methadone is a long-acting opioid used in the treatment of various pain states and substitution therapy in heroin addiction. "	( Characterization of the antinociceptive effects of the individual isomers of methadone after acute and chronic administrations. Morgan, RW; Nicholson, KL, 2011)	2.04
"Methadone is an effective analgesic opioid that may have a place for the treatment of pain in horses. "	( The effect of P-glycoprotein on methadone hydrochloride flux in equine intestinal mucosa. Andrews, FM; Linardi, RL; Stokes, AM, 2013)	2.12
"Methadone is a synthetic opiate that is useful in a variety of clinical settings, including in maintenance therapy of heroin dependence and as an analgesic. "	( Methadone does not alter key parameters of adult hippocampal neurogenesis in the heroin-naïve rat. Andersen, JM; Eisch, AJ; Masiulis, I; Mørland, J; Richardson, DR; Sankararaman, A, 2012)	3.26
"Methadone prescription is a controversial topic. "	( Methadone replacement therapy: tried, tested, effective? Daniels, AM; Robertson, JR, 2012)	3.26
"Methadone dependence is a risk factor for poor bowel visualization and leads to more repeat colonoscopies. "	( Chronic methadone use, poor bowel visualization and failed colonoscopy: a preliminary study. Bernstein, B; Beyda, DJ; Fogel, J; Mohanty, SR; Notar-Francesco, V; Verma, S, 2012)	2.26
"Methadone is a uniquely complex opioid, responsible for a disproportionate percentage of opioid-related morbidity and mortality."	( Methadone in the chronic pain patient with a substance use disorder. Friedman, CK; Reisfield, GM, 2012)	2.54
"Methadone continues to be a widely used maintenance therapy for opiate dependence. "	( Bilateral acute necrosis of the globi pallidi and rhabdomyolysis due to combined methadone and benzodiazepine toxicity. Corliss, RF; Mandal, R; Soriano, BJ, 2013)	2.06
"Methadone is a synthetic narcotic used in opioid dependent situations. "	( [Methadone poisoning in a 1-year-old child treated by continuous infusion of naloxone]. Benbrick, N; Leblanc, A; Moreau, MH, 2002)	2.67
"Methadone is an effective treatment for opioid dependency and chronic pain. "	( Torsade de pointes associated with very-high-dose methadone. Hays, H; Krantz, MJ; Lewkowiez, L; Mehler, PS; Robertson, AD; Woodroffe, MA, 2002)	2.01
"Methadone is an effective maintenance therapy intervention for the treatment of heroin dependence as it retains patients in treatment and decreases heroin use better than treatments that do not utilise opioid replacement therapy. "	( Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Breen, C; Davoli, M; Kimber, J; Mattick, RP, 2002)	3.2
"Methadone hydrochloride is an opiate that has pharmacodynamic and pharmacokinetic properties that suggest it may provide longer analgesia than morphine when administered via the intra-articular route. "	( An evaluation of the histological effects of intra-articular methadone in the canine model. Hand, WR; Herbert, D; Jones, TA; Pellegrini, JE; Ports, MD; Unger, DV, 2003)	2
"Methadone is an effective maintenance therapy intervention for the treatment of heroin dependence as it retains patients in treatment and decreases heroin use better than treatments that do not utilise opioid replacement therapy. "	( Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Breen, C; Davoli, M; Kimber, J; Mattick, RP, 2003)	3.2
"Methadone is a clinically used opioid agonist that is oxidatively metabolized by cytochrome P450 (CYP) isoforms to a stable metabolite, EDDP. "	( Stereoselective metabolism of methadone N-demethylation by cytochrome P4502B6 and 2C19. Gal, J; Gerber, JG; Rhodes, RJ, 2004)	2.05
"Methadone hydrochloride is a mu-opioid agonist that has been used for the treatment of pain and for the management and maintenance of opioid withdrawal for over 50 years. "	( Clinical use of methadone. Goode, JV; Layson-Wolf, C; Small, RE, 2002)	2.1
"Methadone (MTD) is a chiral drug widely used for the treatment of opioid dependence for which a rapid analytical method for the determination of each enantiomer would be advantageous. "	( Automated LC-MS method for the fast stereoselective determination of methadone in plasma. Eap, C; Rudaz, S; Souverain, S; Veuthey, JL, 2003)	2
"Methadone is a well-established maintenance drug for the therapy of opioid addicts. "	( [Intoxication with methadone and benzodiazepines in a morbidly obese patient in the social environment of a heroin addict receiving methadone maintenance therapy]. Hammer, B; Kleinschmidt, S; Risch, B; Wilhelm, W, 2004)	2.09
"Methadone is a strong opioid analgesic that is finding increasing use in chronic pain therapeutics. "	( Functional inhibition by methadone of N-methyl-D-aspartate receptors expressed in Xenopus oocytes: stereospecific and subunit effects. Au, JD; Callahan, RJ; Liu, C; Paul, M; Yost, CS, 2004)	2.07
"Methadone is an opiate drug that has been identified as an in-vitro substrate of the efflux pump P-glycoprotein (P-gp), active in the intestinal epithelium and in the blood-brain barrier (BBB), among other sites. "	( Effect of P-glycoprotein inhibition on methadone analgesia and brain distribution in the rat. Calvo, R; Lukas, JC; Ortega, I; Rodriguez, M; Soengas, I; Suarez, E, 2004)	2.04
"Methadone is an opioid used in the management of cancer pain both in opioid naïve patients and in rotation from other opioids. "	( Methadone for cancer pain. Nicholson, AB, 2004)	3.21
"Methadone is a widely used synthetic opioid which is administered as a racemic mixture of (R)-(--)- and (S)-(+)-enantiomers, with only (R)-(--)-methadone possessing mu opioid receptor agonist activity. "	( (S)-(+)-methadone is more immunosuppressive than the potent analgesic (R)-(--)-methadone. Hutchinson, MR; Somogyi, AA, 2004)	2.2
"Methadone is a synthetic opioid, used both as an analgesic in severe pain relief and now mainly in the treatment of opiate dependence. "	( The effects of methadone and its role in fatalities. Corkery, JM; Ghodse, AH; Oyefeso, A; Schifano, F, 2004)	2.12
"Methadone is a basic drug highly bound to alpha1-acid glycoprotein (AGP), a plasma protein that increases in several pathological situations. "	( Alpha-1-acid glycoprotein directly affects the pharmacokinetics and the analgesic effect of methadone in the rat beyond protein binding. Calvo, R; Leal, N; Lukas, JC; Ortega, I; Rodriguez, M; Soengas, I; Suarez, E, 2004)	1.99
"Methadone maintenance is an effective and most widely used treatment for opiate addiction, allowing normalization of many physiological abnormalities caused by chronic use of short-acting opiates."	( Pharmacogenetics and human molecular genetics of opiate and cocaine addictions and their treatments. Bart, G; Kreek, MJ; LaForge, KS; Lilly, C; Nielsen, DA, 2005)	1.05
"Methadone is a synthetic opioid with potent analgesic effects. "	( Methadone treatment for pain states. Kral, LA; Toombs, JD, 2005)	3.21
"Methadone is a synthetic opioid that counteracts withdrawal symptoms of heroin."	( Methadone and buprenorphine maintenance therapies for patients with hepatitis C virus infected after intravenous drug use. Buntinx, F; Matheï, C; Robaeys, G; Verrando, R, )	2.3
"Methadone is an opioid with complex properties, and a patient that is taking methadone can represent a unique challenge to the anesthesiologist. "	( Review article: perioperative pain management of patients on methadone therapy. Gourlay, D; Peng, PW; Tumber, PS, 2005)	2.01
"(1) Methadone is an opiate used for replacement therapy of opiate addiction that causes dose-dependent QT prolongation. "	( Torsades de pointes with methadone. , 2005)	1.19
"Methadone is a synthetic opiate derivative that possesses analgesic activity. "	( Validation of a high-pressure liquid chromatography and fluorescence polarization immunoassay for the determination of methadone in canine plasma. KuKanich, B; Papich, MG; X Lascelles, BD, 2005)	1.98
"Methadone is a synthetic opioid frequently used in drug maintenance programs for heroin addicts. "	( Methadone-induced Torsade de pointes tachycardias. Ammann, P; Maeder, M; Osswald, S; Schaer, BA; Sticherling, C, 2005)	3.21
"(-)-Methadone acts as an agonist at opioid receptors. "	( Methadone increases intracellular calcium in SH-SY5Y and SH-EP1-halpha7 cells by activating neuronal nicotinic acetylcholine receptors. Ahtee, L; Korpi, ER; Kylänlahti, I; Lukas, RJ; Möykkynen, T; Nousiainen, H; Pakkanen, JS; Peng, JH; Tuominen, RK; Yli-Kauhaluoma, J, 2005)	2.33
"Methadone is a synthetic opioid analgesic that is used as an alternate to morphine and hydromorphone for patients with severe pain. "	( Pharmacology of methadone and its isomers. Inturrisi, CE, )	1.92
"Methadone is a strong opioid analgesic that has been used successfully in cancer pain management. "	( Intermittent subcutaneous methadone administration in the management of cancer pain. Centeno, C; Vara, F, 2005)	2.07
"Methadone is a synthetic opioid agonist and N-methyl-D-aspartate (NMDA) receptor antagonist that is being increasingly used in pain management, particularly for pain that is resistant to conventional opioids. "	( Rotation to methadone after opioid dose escalation: How should individualization of dosing occur? Booth, CM; Cottrell, W; Seccareccia, D; Zimmermann, C, 2005)	2.15
"Methadone is a long-acting mu-opioid and is an effective treatment for heroin addiction. "	( Ventilatory responses to hypoxia and hypercapnia in stable methadone maintenance treatment patients. Cunnington, D; Drummer, OH; Kronborg, I; Quinnell, T; Teichtahl, H; Tran, H; Wang, D, 2005)	2.01
"Methadone is an opioid, which has a high oral bioavailability (>70%) and a long elimination half-life (>20 h) in human beings. "	( The effects of inhibiting cytochrome P450 3A, p-glycoprotein, and gastric acid secretion on the oral bioavailability of methadone in dogs. Aman, AM; Kukanich, B; Lascelles, BD; Mealey, KL; Papich, MG, 2005)	1.98
"Methadone is a synthetic opioid that has been used successfully to treat heroin addiction and chronic pain. "	( [Torsades de pointes during methadone treatment]. Almendral Garrote, J; Arenal Maíz, A; Atienza Fernández, F; González Torrecilla, E; Puchol Calderón, A; Sánchez Hernández, AM, 2005)	2.07
"Methadone is a synthetic opiate used in the treatment of opiate addiction. "	( Dental management of patients taking methadone. Graham, CH; Meechan, JG, 2005)	2.04
"Methadone is a synthetic opioid that is effective for the relief of moderate-to-severe pain and for the treatment of opioid dependence. "	( Pharmacokinetics of methadone. Kern, SE; Lugo, RA; Satterfield, KL, 2005)	2.09
"Methadone is a substrate for the P-glycoprotein transporter, encoded by the ABCB1 gene, which regulates central nervous system exposure."	( ABCB1 genetic variability and methadone dosage requirements in opioid-dependent individuals. Barratt, DT; Coller, JK; Dahlen, K; Loennechen, MH; Somogyi, AA, 2006)	1.34
"Methadone is a unique mu opioid agonist, which also has delta receptor affinity and properties of N-methyl-D-aspartate receptor antagonism and monoamine reuptake inhibition. "	( Methadone for treatment of cancer pain. Bryson, J; Seccareccia, D; Tamber, A; Zimmermann, C, 2006)	3.22
"Methadone treatment is a well recognised cause of QT interval lengthening in adults. "	( Maternal methadone may cause arrhythmias in neonates. Ewer, AK; Hussain, T, 2007)	2.2
"Oral methadone therapy is an effective and increasingly popular treatment for opioid dependency and chronic pain. "	( QTc prolongation and torsades de pointes associated with methadone therapy. Brooks, DE; Katz, KD; Routhier, DD, 2007)	1.1
"Methadone is a recommended treatment for pregnant women wishing to discontinue their use of heroin."	( Perinatal care of women maintained on methadone. Goff, M; O'Connor, M, )	1.12
"Methadone is an opiate used as part of the treatment for heroin abuse; it can be ingested orally. "	( Fatal methadone intoxication in a child. Cuellar, H; Descartes, F; Kumfa, P; Riascos, R; Rojas, R, 2008)	2.27
"Methadone is an opioid used in the management of cancer pain. "	( Methadone for cancer pain. Nicholson, AB, 2007)	3.23
"Methadone hydrochloride is an effective, inexpensive, and relatively safe opioid to use in the treatment of patients with chronic pain. "	( Prescribing methadone for pain management in end-of-life care. Manfredonia, JF, 2005)	2.15
"Methadone is an interesting analgesic for multiple reasons. "	( The safety of methadone hydrochloride. Swegle, JM; Wensel, DD, 2008)	2.15
"Methadone is a recognised cause of this potentially fatal cardiac arrhythmia which is more likely to occur when methadone metabolism is inhibited by drugs such as HIV tease inhibitors."	( Methadone induced torsade de pointes in a patient receiving antiretroviral therapy. Barry, M; Falconer, M; Ingerhaug, J; Molloy, D, )	2.3
"Methadone is a P-gp substrate, and, although there are inconsistent reports, ABCB1 genetic polymorphisms also contribute slightly to the interindividual variability of methadone kinetics and influence dose requirements."	( Interindividual variability of methadone response: impact of genetic polymorphism. Davani, S; Gerritsen-van Schieveen, P; Kantelip, JP; Li, Y, 2008)	1.35
"Methadone is a mu-opioid receptor agonist used for treating opiate dependence. "	( ABCB1 (MDR1) genetic variants are associated with methadone doses required for effective treatment of heroin dependence. Adelson, M; Barral, S; Borg, L; Kreek, MJ; Levran, O; Li, D; O'Hara, K; Ott, J; Peles, E; Ray, B, 2008)	2.04
"Methadone is a potent synthetic opioid used for treatment of opioid dependence and chronic pain. "	( Methadone- and heroin-related deaths in Florida. Gold, MS; Goldberger, BA; Graham, NA; Merlo, LJ, 2008)	3.23
"Methadone hydrochloride is an old drug that has been in vogue off and on. "	( Methadone. Bull, J; Chhabra, S, )	3.02
"Methadone is a synthetic narcotic analgesic used as a substitute for Heroin in drug detoxification programs."	( Genetic screening of compounds used in drug abuse treatment. II. Methadone. Braude, M; Brockman, H; Brusick, D; Hung, C; Jagannath, D; Matheson, D, 1981)	1.22
"Methadone is a potent, long acting narcotic analgesic which can be orally administered due to its almost complete bioavailability. "	( Preliminary study on the absorption profile after rectal and oral administration of methadone in human volunteers. Fiets, G; Meijer, DK; Moolenaar, F; Visser, J, 1984)	1.93
"Methadone is a useful second-line or third-line opioid for the patient who is highly tolerant to other opioids, as it may demonstrate incomplete cross-tolerance with other agonist opioids."	( Use of methadone in a highly tolerant patient receiving parenteral hydromorphone. Bruera, E; Thomas, Z, 1995)	1.47
"Methadone is a synthetic opioid with excellent oral bioavailability, variable, but long duration of action and extremely low cost. "	( Respiratory depression in a patient receiving oral methadone for cancer pain. Bruera, E; Hunt, G, 1995)	1.99
"Methadone is a potent opioid analgesic that demonstrates incomplete cross-tolerance with other mu-opioid receptor agonist analgesics. "	( Clinical efficacy of methadone in patients refractory to other mu-opioid receptor agonist analgesics for management of terminal cancer pain. Case presentations and discussion of incomplete cross-tolerance among opioid agonist analgesics. Crews, JC; Denson, DD; Sweeney, NJ, 1993)	2.05
"1. Methadone is a synthetic narcotic that relieves the craving for heroin. "	( Methadone anonymous: a 12-step program. Reducing the stigma of methadone use. McGonagle, D, 1994)	2.35
"Methadone is a typical mu-opioid receptor agonist that is widely used for maintenance and detoxification treatment of opiate-dependent patients. "	( Methadone withdrawal psychosis. Galynker, II; Levinson, I; Rosenthal, RN, 1995)	3.18
"Methadone is a synthetic opiate receptor agonist that has been available for more than 40 years. "	( Methadone in the management of cancer pain: a review. Bruera, E; Fainsinger, R; Schoeller, T, 1993)	3.17
"Methadone is a very useful drug in cancer pain because of its low cost, lack of active metabolites, high oral availability, and the rapid onset of its analgesic effect. "	( Patient-controlled analgesia with oral methadone in cancer pain: preliminary report. Caligara, M; Mercadante, S; Sapio, M; Serretta, R, 1996)	2.01
"Methadone is a very potent analgesic drug. "	( Pain perception of intravenous heroin users on maintenance therapy with levomethadone. Gastpar, M; Katta, T; Klöppel, A; Pries, E; Schall, U, 1996)	1.97
"Methadone is a very effective second-line opioid for treatment of cancer pain. "	( Intravenous methadone for cancer pain unrelieved by morphine and hydromorphone: clinical observations. Borsook, D; Chandler, SW; Manfredi, PL; Payne, R, 1997)	2.12
"Methadone is a synthetic opioid agonist considered a second choice drug in the management of cancer pain. "	( An update on the clinical use of methadone for cancer pain. Bruera, E; Ripamonti, C; Zecca, E, 1997)	2.02
"Oral methadone is considered to be a valid opioid analgesic alternative to morphine and hydromorphone in treating cancer pain. "	( Equianalgesic dose/ratio between methadone and other opioid agonists in cancer pain: comparison of two clinical experiences. Belzile, M; Bruera, E; De Conno, F; Groff, L; Hanson, J; Pereira, J; Ripamonti, C, 1998)	1.1
"Methadone is a drug of indisputable value in the treatment of cancer pain, and an unbalanced focus on the risks of inappropriate use rather than the benefits should not compromise the use of a relevant alternative to morphine in the management of cancer pain."	( Morphine versus methadone in the pain treatment of advanced-cancer patients followed up at home. Agnello, A; Barresi, L; Calderone, L; Casuccio, A; Mercadante, S; Serretta, R, 1998)	2.09
"Like methadone, there is a dose/efficacy relationship."	( [Substitution therapy of drug addicts]. Kopferschmitt, J; Weber, JC, 1998)	0.76
"Methadone maintenance is a treatment program designed for chronic heroin addicted patients. "	( Methadone maintenance: results of treatment in heroin addict at Thanyarak Hospital (1990-1996). Dechongkit, S; Lukanapichonchut, L; Patarakorn, A; Verachai, V, 1998)	3.19
"Methadone is a synthetic opioid agonist which has been available for more than 40 years. "	( [Methadone as an analgesic]. Clausen, T; Eriksen, J; Kamp-Jensen, M, 2000)	2.66
"Methadone is a unique opioid with several special properties besides being a mu agonist, which makes for difficulty in the calculation of equianalgesic doses. "	( Methadone as a rescue for failed high-dose opiate therapy for catastrophic pain. Davis, MP, 2000)	3.19
"Methadone is a mu-opioid receptor agonist reported to relieve pain unresponsive to other opioids."	( Neuronal inhibitory effects of methadone are predominantly opioid receptor mediated in the rat spinal cord in vivo. Carpenter, KJ; Chapman, V; Dickenson, AH, 2000)	1.31
"Methadone is a synthetic opioid agonist which is mostly used for drug maintenance therapy in opioid addicts. "	( [Use of methadone as analgesic]. Donnadieu, S, 2000)	2.18
"Methadone is a synthetic opioid, with mu and delta receptor activity, associated with the capacity to inhibit N-methyl-D-aspartate receptors."	( Opioid switch to oral methadone in cancer pain. Body, JJ; Lossignol, DA; Mancini, I, 2000)	1.34
"Methadone is a 50:50 mixture of two enantiomers and (R)-methadone accounts for the majority of its opioid effect. "	( Plasma concentrations of the enantiomers of methadone and therapeutic response in methadone maintenance treatment. Baumann, P; Bourquin, M; Déglon, J; Eap, CB; Livoti, S; Martin, J; Powell, K; Spagnoli, J, 2000)	2.01
"Methadone is a potent synthetic opioid analgesic best known in Australia as maintenance therapy for narcotic addicts. "	( The rediscovery of methadone for cancer pain management. Ayonrinde, OT; Bridge, DT, 2000)	2.08
"Methadone appears to be a CYP3A inhibitor in vivo following a single oral dose and measurements of the urinary cortisol ratio appear to be a useful index to follow this inhibition."	( A single dose of methadone inhibits cytochrome P-4503A activity in healthy volunteers as assessed by the urinary cortisol ratio. Arnaud, P; Boulton, DW; DeVane, CL, 2001)	2.09
"Methadone is an effective treatment for heroin addiction; however, insufficient information is available on its interactions with HAART."	( Methadone and antiretroviral medications, part I. Friedland, GH; Gourevitch, MN, 1999)	2.47
"Methadone is a potent analgesic and sedative. "	( Determination of methadone in urine using ion trap GC/MS in positive ion chemical ionization mode. Guzaldo, F; Hussain, MJ; Lewis, D; Moore, C, 2001)	2.09
"Methadone maintenance is an effective treatment for opioid dependence, yet its use is restricted to federally licensed narcotic treatment programs (NTPs). "	( Methadone maintenance in primary care: a randomized controlled trial. Chawarski, M; Fiellin, DA; O'Connor, PG; Pakes, JP; Pantalon, MV; Schottenfeld, RS, 2001)	3.2
"Methadone is an inexpensive and highly effective analgesic when titrated appropriately. "	( Conversion from intrathecal morphine to oral methadone. Gebhardt, R; Kinney, MA, )	1.83
"Methadone is an effective analgesic whose pharmacokinetics must be appreciated in order for it to be used safely and effectively."	( Important clinical pharmacologic considerations in the use of methadone in cancer patients. Ettinger, DS; Trump, DL; Vitale, PJ, 1979)	1.22
"Methadone maintenance is an important component of the management of many pregnant opioid addicts."	( Narcotic use in pregnancy. Hoegerman, G; Schnoll, S, 1991)	1
"Methadone alone is a good analgesic agent that has slight effects in the form of respiratory depression, to which partial tolerance builds up in the course of long-term use of the drug."	( [Methadone--pharmacokinetics and pharmacodynamics of an opiate]. Jage, J, 1989)	1.91

Effects

Methadone has a number of unique characteristics including excellent oral and rectal absorption, no known active metabolites, high potency, low cost, and longer administration intervals. Methadone holds a niche role in the management of opioid-induced hyperalgesia and central sensitization.

Methadone and buprenorphine maintenance treatments significantly improve maternal, fetal and neonatal outcomes. Methadone has been increasingly used in the treatment of refractory cancer pain with different conversion methods and ratios described.

Excerpt	Reference	Relevance
"Methadone has a unique pharmacodynamic profile: it is both a μ-agonist and an NMDAr-blocker."	( Methadone for postoperative analgesia: contribution of N-methyl-D-aspartate receptor antagonism: A randomised controlled trial. Galeone, C; Mariani, L; Motta, G; Proto, PL; Tognoli, E; Valenza, F, 2020)	2.72
"Methadone has a unique mechanism of action when compared with all other opioids and for this reason methadone has come to hold a niche role in the management of opioid-induced hyperalgesia and central sensitization."	( Methadone for Pain Management: A Pharmacotherapeutic Review. Kreutzwiser, D; Tawfic, QA, 2020)	2.72
"Methadone has a wide pharmacokinetic interindividual variability, resulting in unpredicted treatment response. "	( Pharmacogenomics biomarkers for personalized methadone maintenance treatment: The mechanism and its potential use. Ramli, FF, 2021)	2.32
"Methadone has a long history of pain relief and successful substitute for maintenance treatment in heroin and narcotic addiction. "	( Forensic Toxicology Perspectives of Methadone-associated Deaths in Tehran, Iran, a 7-year Overview. Akhgari, M; Amini-Shirazi, N; Iravani, FS, 2018)	2.2
"R-methadone has a stronger interaction with S-β-CD than S-methadone."	( Computer simulation and enantioselective capillary electrophoresis to characterize isomer mixtures of sulfated β-cyclodextrins. Caslavska, J; Hruška, V; Mikkonen, S; Thormann, W, 2018)	1.04
"Methadone has a higher capability to induce long QT interval and dangerous arrhythmias in conventional doses than others."	( Opioids and Cardiac Arrhythmia: A Literature Review. Behzadi, M; Beik, A; Joukar, S, 2018)	1.2
"Methadone has an important role in the management of cancer pain, with many advantages including low cost, high oral bioavailability, rapid onset of action, once-daily dosing, and postulated benefits in difficult pain control scenarios."	( Therapeutic challenges in cancer pain management: a systematic review of methadone. Afsharimani, B; Good, P; Hardy, J; Haywood, A; Khan, S; Movva, R, 2014)	1.36
"Methadone also has a long elimination half-life (19 [SD 14] hours) and NMDA receptor activity although dose administration is complicated by highly variable morphine equianalgesic equivalence (1 : 2.5-20)."	( Pediatric palliative care: use of opioids for the management of pain. Anderson, BJ; Craig, F; Michel, E; Zernikow, B, 2009)	1.07
"Methadone has a long and successful history in the treatment of opioid addiction. "	( Trends in methadone-related deaths in Zurich. Bartsch, C; Laberke, PJ, 2010)	2.21
"Methadone maintenance has an important role in the treatment of injecting heroin users and the reduction of harm connected to drug abuse. "	( [Monitoring and evaluation of the Hungarian methadone maintenance programmes]. Márványkövi, F; Melles, K; Rácz, J; Vadász, V, 2010)	2.06
"Methadone has a mean bioavailability of around 75% (range 36-100%)."	( Interindividual variability of the clinical pharmacokinetics of methadone: implications for the treatment of opioid dependence. Baumann, P; Buclin, T; Eap, CB, 2002)	1.27
"(3) Methadone has a long plasma elimination half-life, and this poses a risk of accumulation."	( Torsades de pointes with methadone. , 2005)	1.11
"Methadone has an asymmetric carbon atom resulting in 2 enantiomeric forms, the d and l isomers."	( Pharmacology of methadone and its isomers. Inturrisi, CE, )	1.2
"R-methadone has a receptor binding profile which resembles that of morphine."	( The mu1, mu2, delta, kappa opioid receptor binding profiles of methadone stereoisomers and morphine. Christensen, CB; Christrup, LL; Kristensen, K, 1995)	1.09
"Methadone has a number of unique characteristics including excellent oral and rectal absorption, no known active metabolites, high potency, low cost, and longer administration intervals, as well as an incomplete cross-tolerance with respect to other mu-opioid receptor agonist drugs."	( An update on the clinical use of methadone for cancer pain. Bruera, E; Ripamonti, C; Zecca, E, 1997)	1.3
"Methadone has an average primary-phase half-life of 14.3 hours and a slower secondary-phase half-life averaging 54.8 hours."	( Important clinical pharmacologic considerations in the use of methadone in cancer patients. Ettinger, DS; Trump, DL; Vitale, PJ, 1979)	1.22
"Oral methadone has the strongest evidence for effectiveness."	( Medication Treatment of Opioid Use Disorder. Bell, J; Strang, J, 2020)	1.01
"Methadone has been prescribed in France as opioid substitution therapy as a syrup formulation since 1995 and as capsules since 2008. "	( Methadone poisonings: a seven-year retrospective study of the French poison center network focusing on suicide attempts vs. misuses. Bloch, J; de Haro, L; Glaizal, M; Nisse, P; Richard, N; Simon, N; Sinno-Tellier, S; Torrents, R; Vodovar, D, 2020)	3.44
"Methadone has been increasingly used in the treatment of refractory cancer pain with different conversion methods and ratios described.A retrospective chart review of patients on methadone for cancer pain was conducted to assess its use as the primary opioid, focusing on pain characteristics, opioid rotation indication, previous analgesics, adverse effects and final methadone dose in comparison with the pre-rotation Morphine Equivalent Daily Dose (MEDD).Eight patients were rotated to methadone due to refractory moderate-severe cancer pain and achieved good pain relief. "	( Opioid Rotation to Methadone for Refractory Cancer Pain: A Case Series. Aziz, FA; Khoo, SY; Nambbiar, P, )	1.9
"Methadone has unique characteristics that make it an attractive agent for the treatment of chronic pain and opioid drug dependence. "	( Levorphanol versus methadone use: safety considerations. Haider, A; Reddy, A, 2020)	2.33
"Methadone has a unique pharmacodynamic profile: it is both a μ-agonist and an NMDAr-blocker."	( Methadone for postoperative analgesia: contribution of N-methyl-D-aspartate receptor antagonism: A randomised controlled trial. Galeone, C; Mariani, L; Motta, G; Proto, PL; Tognoli, E; Valenza, F, 2020)	2.72
"Methadone has a unique mechanism of action when compared with all other opioids and for this reason methadone has come to hold a niche role in the management of opioid-induced hyperalgesia and central sensitization."	( Methadone for Pain Management: A Pharmacotherapeutic Review. Kreutzwiser, D; Tawfic, QA, 2020)	2.72
"Methadone has a wide pharmacokinetic interindividual variability, resulting in unpredicted treatment response. "	( Pharmacogenomics biomarkers for personalized methadone maintenance treatment: The mechanism and its potential use. Ramli, FF, 2021)	2.32
"Methadone has been associated with prolongation of the QTc interval (QTc) on electrocardiogram (ECG). "	( Effect of methadone on QTc in infants. Arora, G; Maurer, S; May, C; Miller, M; Riley, M; Shenk, J; Snyder, K, 2021)	2.47
"Methadone has many characteristics that differentiate it from other opioids, which suggests that it may have a different efficacy and safety profile."	( Methadone for neuropathic pain in adults. Ferguson, MC; McNicol, ED; Schumann, R, 2017)	2.62
"Methadone has been shown to be effective for cancer pain. "	( Clinical Outcomes of Start-Low, Go-Slow Methadone Initiation for Cancer-Related Pain: What's the Hurry? Chow, L; Fyles, G; Hawley, P; Mittelstadt, M; O'Leary, MJ; Shokoohi, A, 2017)	2.17
"Methadone has a long history of pain relief and successful substitute for maintenance treatment in heroin and narcotic addiction. "	( Forensic Toxicology Perspectives of Methadone-associated Deaths in Tehran, Iran, a 7-year Overview. Akhgari, M; Amini-Shirazi, N; Iravani, FS, 2018)	2.2
"R-methadone has a stronger interaction with S-β-CD than S-methadone."	( Computer simulation and enantioselective capillary electrophoresis to characterize isomer mixtures of sulfated β-cyclodextrins. Caslavska, J; Hruška, V; Mikkonen, S; Thormann, W, 2018)	1.04
"Methadone has been recognized as an effective maintenance treatment for opioid dependence. "	( Plasma Testosterone and Sexual Function in Southeast Asian Men Receiving Methadone and Buprenorphine Maintenance Treatment. Danaee, M; Loh, HS; Ng, CG; Riahi, S; Sulaiman, AH; Yee, A, 2018)	2.16
"Methadone has been recognized as a unique option for treatment of surgical pain due to its multiple mechanisms of analgesia and its potential to decrease tolerance to other opioids."	( Use of Methadone to Reverse Opioid Escalation in a Patient With Surgical Pain. Chandler, M; Cunningham, G; Jaffar, M; Webb, T, 2018)	1.66
"Methadone has a higher capability to induce long QT interval and dangerous arrhythmias in conventional doses than others."	( Opioids and Cardiac Arrhythmia: A Literature Review. Behzadi, M; Beik, A; Joukar, S, 2018)	1.2
"Methadone has several unique characteristics that make it an attractive option for pain relief in serious illness, but the safety of methadone has been called into question after reports of a disproportionate increase in opioid-induced deaths in recent years. "	( Safe and Appropriate Use of Methadone in Hospice and Palliative Care: Expert Consensus White Paper. Bemben, NM; Bruera, E; Chou, R; Davis, MP; Lapointe, BJ; Lockman, DK; Malotte, K; McPherson, ML; Paice, J; Ray, JB; Reddy, A; Salpeter, S; Walker, KA; Wellman, C, 2019)	2.25
"Methadone has been reported to prolong the corrected QT (QTc) interval and increase the risk of torsades de pointes."	( Corrected QT Interval Prolongation in Pediatric and Young Adult Patients on Methadone for Cancer-Related Pain. Bruera, E; Jo, E; Liu, D; Madden, K; Williams, JL, 2019)	2.19
"Methadone has been effectively utilized in the palliative care setting as a second-line agent for pain management in cancer patients with refractory pain, or in those who cannot tolerate other opioid medications. "	( Preliminary Validation for the "BJR method"-A Possible New Mathematical Approach to Methadone Conversion. Baumrucker, SJ; Hutchinson, L; Trofimovitch, D, )	1.8
"Methadone has several desirable pharmacological features, including a long elimination half-life."	( Intraoperative methadone for postoperative pain after laparoscopic hysterectomy: Protocol for a randomised, double-blind trial. Brix, LD; Friesgaard, KD; Kristensen, CB; Nikolajsen, L; Rian, O, 2019)	1.59
"Methadone has been the most commonly used pharmacotherapy for the treatment of opioid dependence in U.S. "	( Retention in methadone and buprenorphine treatment among African Americans. Gryczynski, J; Jaffe, JH; Kelly, SM; Mitchell, SG; Myers, CP; O'Grady, KE; Olsen, YK; Schwartz, RP, 2013)	2.2
"Methadone has been used as a pharmacotherapy for the treatment of opiate dependence since the mid-1960s. "	( Methadone maintenance treatment and cognitive function: a systematic review. Russell, BR; Wang, GY; Wouldes, TA, 2013)	3.28
"Methadone has been reported to be as effective as morphine for cancer pain management. "	( Methadone rotation for cancer patients with refractory pain in a palliative care unit: an observational study. Bruera, E; Ciais, JF; Filbet, M; Ledoux, M; Rhondali, W; Tremellat, F, 2013)	3.28
"Methadone has an important role in the management of cancer pain, with many advantages including low cost, high oral bioavailability, rapid onset of action, once-daily dosing, and postulated benefits in difficult pain control scenarios."	( Therapeutic challenges in cancer pain management: a systematic review of methadone. Afsharimani, B; Good, P; Hardy, J; Haywood, A; Khan, S; Movva, R, 2014)	1.36
"Methadone has been associated with QTc prolongation and ventricular arrhythmias but the prevalence of QTc prolongation and association with ventricular arrhythmias remains unclear. "	( Methadone Therapy in Underserved Urban Community: QTc Prolongation and Life-Threatening Ventricular Arrhythmias. Cheng, A; Chowdhury, M; Khilkin, M; Palma, E; Wong, J, 2015)	3.3
"Methadone has been used to treat opiate dependence since the mid-1960s. "	( Resting EEG and ERPs findings in methadone-substituted opiate users: a review. Kydd, R; Russell, BR; Wang, GY, 2015)	2.14
"Methadone has been a stalwart pharmacologic option for the management of opioid drug dependence for many years. "	( Is levorphanol a better option than methadone? Fudin, J; Pham, TC; Raffa, RB, 2015)	2.13
"Methadone has been the mainstay of maintenance treatment for nearly 50 years, but recent research has found that both methadone and buprenorphine maintenance treatments significantly improve maternal, fetal and neonatal outcomes."	( Pharmacological Management of Opioid Use Disorder in Pregnant Women. Wilder, CM; Winhusen, T, 2015)	1.14
"Methadone has long been regarded as an effective treatment for opioid dependence. "	( Sexual Dysfunction in Heroin Dependents: A Comparison between Methadone and Buprenorphine Maintenance Treatment. Danaee, M; Loh, HS; Ng, CG; Sulaiman, AH; Yee, A, 2016)	2.12
"Methadone has been associated with lower overall survival (OS) in patients with chronic pain. "	( Overall Survival among Cancer Patients Undergoing Opioid Rotation to Methadone Compared to Other Opioids. Bruera, E; de la Cruz, M; Liu, D; Reddy, A; Schuler, US; Wu, J; Yennurajalingam, S, 2017)	2.13
"Methadone has higher treatment retention rates than buprenorphine-naloxone does, while buprenorphine-naloxone has a lower risk of overdose."	( Primary care management of opioid use disorders: Abstinence, methadone, or buprenorphine-naloxone? Kahan, M; Nader, M; Srivastava, A, 2017)	1.42
"Methadone has been increasingly used for analgesia in the last 10 years."	( Methadone: an effective, safe drug of first choice for pain management in frail older adults. Gallagher, R, 2009)	2.52
"Methadone also has a long elimination half-life (19 [SD 14] hours) and NMDA receptor activity although dose administration is complicated by highly variable morphine equianalgesic equivalence (1 : 2.5-20)."	( Pediatric palliative care: use of opioids for the management of pain. Anderson, BJ; Craig, F; Michel, E; Zernikow, B, 2009)	1.07
"Methadone has been shown to increase cigarette smoking in a dose-dependent manner, whereas smoking/nicotine has been shown to increase methadone self-administration and reinforcing properties."	( Methadone-nicotine interactions in methadone maintenance treatment patients. Brands, B; Elkader, AK; Selby, P; Sproule, BA, 2009)	2.52
"Methadone has been used as a successful pharmacologic intervention for the treatment of heroin dependence and acute and chronic pain."	( [Methadone treatment and its dangers]. Jodziūniene, L; Lazauskas, R; Reingardiene, D, 2009)	1.98
"Methadone has additional pharmacologic and toxicologic properties which may complicate the assessment and treatment in overdose situations."	( A case of serotonin syndrome associated with methadone overdose. Martinez, DN; Martinez, TT, 2008)	1.33
"Oral methadone has been successfully used in human medicine and may overcome some limitations of other analgesics in equine species for producing analgesia with minimal adverse effects."	( Pharmacokinetics of the injectable formulation of methadone hydrochloride administered orally in horses. Barker, SA; Hosgood, G; Linardi, RL; Natalini, CC; Short, C; Stokes, AM, 2009)	1.06
"Methadone dosing has been an issue of controversy among clinicians for a long time. "	( High dose versus moderate dose methadone maintenance: is there a better outcome? Amar, R; Casarella, J; Drexler, K; Fareed, A; Roberts, M; Sleboda, M; Vayalapalli, S, 2009)	2.08
"Methadone has a long and successful history in the treatment of opioid addiction. "	( Trends in methadone-related deaths in Zurich. Bartsch, C; Laberke, PJ, 2010)	2.21
"Methadone maintenance has an important role in the treatment of injecting heroin users and the reduction of harm connected to drug abuse. "	( [Monitoring and evaluation of the Hungarian methadone maintenance programmes]. Márványkövi, F; Melles, K; Rácz, J; Vadász, V, 2010)	2.06
"Methadone has been the standard medication for the management of heroin craving."	( Heroin anticraving medications: a systematic review. Amar, R; Casarella, J; Drexler, K; Fareed, A; Vayalapalli, S, 2010)	1.08
"Methadone has been used for many years in the clinical setting and has many well-described side effects. "	( Methadone, another cause of opioid-associated hearing loss: a case report. Babu, KM; Hack, JB; Shaw, KA, 2011)	3.25
"Methadone has previously been found present in exhaled breath of methadone treated patients. "	( Demonstration that methadone is being present in the exhaled breath aerosol fraction. Beck, O; Franck, J; Sandqvist, S, 2011)	2.14
"Methadone has no effect on working memory and executive functions in the patients with a history of heroin use during maintenance treatment intervention."	( [Effects of methadone maintenance treatment on working memory in male heroin dependent patients]. Dai, J; Li, ZA; Pang, LJ; Tang, WC; Wang, SM; Yin, LS; Zhang, L; Zhu, CY, 2012)	1.48
"Methadone has many characteristics that differentiate it from other opioids, which suggests that it may have a different efficacy and safety profile."	( Methadone for chronic non-cancer pain in adults. Haroutiunian, S; Lipman, AG; McNicol, ED, 2012)	2.54
"Methadone treatment has been 'programmatic', with a one-size-fits-all approach that in part reflects the perceived need to impose discipline on deviant individuals."	( Pharmacological maintenance treatments of opiate addiction. Bell, J, 2014)	1.12
"Methadone programs have been organized in each Spanish region in a specific way. "	( [Costs-analysis of methadone program in the autonomous community La Rioja, Spain]. Antoñanzas Villar, F; Del Pozo Iribarría, J; Murga García, JA; Soldevilla Iñiguez, D, 2012)	2.15
"Methadone has a mean bioavailability of around 75% (range 36-100%)."	( Interindividual variability of the clinical pharmacokinetics of methadone: implications for the treatment of opioid dependence. Baumann, P; Buclin, T; Eap, CB, 2002)	1.27
"Methadone has been used as an alternative strong opioid to morphine in the management of cancer pain. "	( An ad libitum schedule for conversion of morphine to methadone in advanced cancer patients: an open uncontrolled prospective study in a Chinese population. Ma, HM; Ng, DK; Sham, MM; Tse, DM, 2003)	2.01
"Methadone treatment has been shown to be an effective intervention that can lower the risk of heroin-induced overdose death. "	( Overdose deaths attributed to methadone and heroin in New York City, 1990-1998. Bryant, WK; Galea, S; Markham Piper, T; Tardiff, KJ; Tracy, M; Vlahov, D, 2004)	2.05
"(3) Methadone has a long plasma elimination half-life, and this poses a risk of accumulation."	( Torsades de pointes with methadone. , 2005)	1.11
"Methadone has an asymmetric carbon atom resulting in 2 enantiomeric forms, the d and l isomers."	( Pharmacology of methadone and its isomers. Inturrisi, CE, )	1.2
"Methadone has been found to inhibit CYP2D6, indicating a potential for interaction with dextromethorphan."	( Dextromethorphan-induced delirium and possible methadone interaction. Lotrich, FE; Pollock, BG; Rosen, J, 2005)	1.31
"Methadone maintenance has been an effective pharmacotherapy for the treatment of heroin dependence for nearly four decades. "	( Methadone doses of 100 mg or greater are more effective than lower doses at suppressing heroin self-administration in opioid-dependent volunteers. Bigelow, GE; Brasser, SM; Donny, EC; Stitzer, ML; Walsh, SL, 2005)	3.21
"Methadone has significant, adverse drug-drug interactions with many antiretroviral therapeutic agents that can contribute to nonadherence and poor clinical outcomes in this high-risk population."	( Treatment of opioid dependence and coinfection with HIV and hepatitis C virus in opioid-dependent patients: the importance of drug interactions between opioids and antiretroviral agents. McCance-Katz, EF, 2005)	1.05
"Methadone has several unique properties that can be beneficial in the treatment of neuropathic pain and cancer pain unresponsive to other opioids, but some of these properties make it very dangerous and difficult to prescribe properly."	( Methadone as an analgesic: a review of the risks and benefits. Johnson, WM; Terpening, CM, )	2.3
"Methadone has been the mainstay of pharmacological management of opioid dependence since the 1960s but buprenorphine is fast gaining acceptance among addiction specialists and patients. "	( Buprenorphine in the treatment of opioid dependence. Day, E; George, S, 2007)	1.78
"R-methadone has a receptor binding profile which resembles that of morphine."	( The mu1, mu2, delta, kappa opioid receptor binding profiles of methadone stereoisomers and morphine. Christensen, CB; Christrup, LL; Kristensen, K, 1995)	1.09
"R-Methadone has been shown to be responsible for most of the pharmacological activity of this drug."	( Sensitive high-performance liquid chromatographic assay with ultraviolet detection of methadone enantiomers in plasma. Norris, RL; Pond, SM; Ravenscroft, PJ, 1994)	1.07
"Methadone maintenance has been used for decades to treat opioid-dependent pregnant women. "	( Methadone treatment during pregnancy. Jarvis, MA; Schnoll, SH, )	3.02
"Methadone has become one of the most widely used drugs for opiate dependency treatment. "	( Involvement of cytochrome P450 3A4 enzyme in the N-demethylation of methadone in human liver microsomes. Bail, JP; Baird, S; Beaune, P; Berthou, F; Dréano, Y; Iribarne, C; Ménez, JF; Picart, D, 1996)	1.97
"Methadone has improved our understanding of these pathologies."	( Treatment of depressive syndromes in detoxified drug addicts: use of methadone. Baylé, FJ; Jalfre, V; Laqueille, X; Lôo, H; Spadone, C, 1996)	1.25
"Methadone has been used for the substitution of heroin addicts since 1964."	( Enantioselective separation of methadone and its main metabolite in human hair by liquid chromatography/ion spray-mass spectrometry. Cirimele, V; Eser, HP; Kintz, P; Mangin, P; Moeller, M; Tracqui, A, 1997)	1.3
"Methadone has a number of unique characteristics including excellent oral and rectal absorption, no known active metabolites, high potency, low cost, and longer administration intervals, as well as an incomplete cross-tolerance with respect to other mu-opioid receptor agonist drugs."	( An update on the clinical use of methadone for cancer pain. Bruera, E; Ripamonti, C; Zecca, E, 1997)	1.3
"Methadone has many pharmacokinetic characteristics that fit it for use in this clinical situation."	( Treatment of pain in chronic bowel subobstruction with self-administration of methadone. Mercadante, S; Sapio, M; Serretta, R, 1997)	1.25
"Methadone has two roles in human immunodeficiency viral infection: pain management and treatment of opioid abuse."	( Methadone withdrawal when starting an antiretroviral regimen including nevirapine. Heelon, MW; Meade, LB, 1999)	2.47
"Methadone has been found to be useful in pain uncontrolled by large doses of conventional opioids such as hydromorphone and morphine. "	( Subcutaneous methadone in terminally ill patients: manageable local toxicity. Mathew, P; Storey, P, 1999)	2.12
"Methadone has been effectively used in the treatment of opiate dependence. "	( A therapeutic use of the methadone fluvoxamine drug interaction. DeMaria, PA; Serota, RD, 1999)	2.05
"Methadone maintenance has been evaluated since its development in 1964 as a medical response to the post-World War II heroin epidemic in New York City. "	( Methadone maintenance treatment (MMT): a review of historical and clinical issues. Joseph, H; Langrod, J; Stancliff, S, )	3.02
"Methadone advocacy has grown into a powerful network of groups working toward the same major goals."	( Methadone advocacy: the voice of the patient. Woods, J, 2001)	2.47
"Methadone has been reported to improve pain relief in patients with morphine resistance, and it is lipophilic and exerts a lesser activity on opioid receptors in the gastrointestinal tract."	( Methadone in treatment of tenesmus not responding to morphine escalation. Dabbene, M; Fulfaro, F; Mercadante, S, 2001)	2.47
"The methadone program has followed 200 patients on continued treatment after incarceration."	( Methadone in provincial prisons in British Columbia. Rothon, DA, )	2.05
"Methadone has its own antibacterial effect, although at supraphysiological concentrations, and is even synergistic with antimicrobial agents against some organisms."	( Methadone: antimicrobial activity and interaction with antibiotics. Barsoum, IS; Lin, MY; Sheagren, JN, 1977)	2.42
"Methadone has an average primary-phase half-life of 14.3 hours and a slower secondary-phase half-life averaging 54.8 hours."	( Important clinical pharmacologic considerations in the use of methadone in cancer patients. Ettinger, DS; Trump, DL; Vitale, PJ, 1979)	1.22
"Methadone chlorhydrate has been administred to opiate addicts either for a short period with a decreasing dosage as a withdrawal cure, or for longterm treatments as a basis of a maintenance program. "	( [A French experience with methadone]. Cuche, H; Deniker, P; Loo, H; Zarifian, E, 1975)	2
"Methadone hydrochloride has been found to be medically safe when administered in the setting of a well-organized heroin addition treatment program. "	( Controlling the abuse of illicit methadone in Washington, DC. Brown, BS; DuPont, RL; Greene, MH, 1975)	1.98
"Also methadone has been shown to be very effective when appropriately used in programs which combine pharmacotherapy with the best elements of "drug free" treatment, that is, counseling and psychological support."	( Rationale for maintenance pharmacotherapy of opiate dependence. Kreek, MJ, 1992)	0.74
"Methadone has been used for substitution in the US."	( [Drug abuse, pregnancy and HIV infection]. Beck, L; Bender, HG; Halberstadt, E; Hartmann, L; Jahn, K, 1991)	0.9
"Methadone maintenance has become the treatment of choice for heroin addiction because of its beneficial effects on illicit opiate use and criminality. "	( A psychoeducational approach to methadone maintenance treatment. Stark, MJ, 1989)	2
"Methadone has been used in hundreds of thousands of patients, in disparate social, economic, cultural, and geographic situations; it has been evaluated in scores of studies."	( Methadone maintenance treatment. Senay, EC, )	2.3

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Methadone can cause a prolonged QTc interval that can lead to ventricular arrhythmias. Methadone was shown to enhance the cytotoxic effects of cisplatin on T24 cells based on the induction of apoptosis.

Excerpt	Reference	Relevance
"iS-methadoneSnFR displays the necessary sensitivity, kinetics, and selectivity─notably enantioselectivity against R-methadone─for biological applications."	( Three Mutations Convert the Selectivity of a Protein Sensor from Nicotinic Agonists to S-Methadone for Use in Cells, Organelles, and Biofluids. Cohen, BN; Dougherty, DA; Kim, CH; Knox, HJ; Lester, HA; Looger, LL; Marvin, JS; Muthusamy, AK; Nichols, AL; Virgil, SC, 2022)	1.46
"The methadone group had a lower mean newborn birthweight (2874±459 g) and a greater incidence of low birth weight (11.4%) than the buprenorphine group (3282±452 g; p<0.001 and 2.5%; p=0.006)."	( Comparison of buprenorphine and methadone in the management of maternal opioid use disorder in full term pregnancies. Davis, JA; Garretto, D; Garry, ET; Herrera, KM; Ly, V; Staszewski, CL, 2020)	1.32
"l-methadone showed a slower elimination rate constant, a lower body clearance, and a smaller steady-state volume of distribution than d-methadone."	( Stereoselective methadone disposition after administration of racemic methadone to anesthetized Shetland ponies assessed by capillary electrophoresis. Braun, C; Gittel, C; Larenza-Menzies, MP; Sandbaumhüter, FA; Theurillat, R; Thormann, W, 2021)	1.53
"Methadone can cause a prolonged QTc interval that can lead to ventricular arrhythmias."	( The frequency of QTc prolongation among pediatric and young adult patients receiving methadone for cancer pain. Bruera, E; Liu, D; Madden, K; Park, M, 2017)	1.4
"Methadone was shown to enhance the cytotoxic effects of cisplatin on T24 cells based on the induction of apoptosis. "	( Impact of Methadone on Cisplatin Treatment of Bladder Cancer Cells. Katzenwadel, A; Kuckuck, I; Michalska, M; Schultze-Seemann, S; Wolf, P, 2018)	2.33
"Methadone did not inhibit mPGES-1 or PTGS2 expression."	( Morphine, but not methadone, inhibits microsomal prostaglandin E synthase-1 and prostaglandin-endoperoxide synthase 2 in lipopolysaccharide-stimulated horse synoviocytes. Ambrósio, CE; Carregaro, AB; Cordeiro, YG; Fukumasu, H; Melo, CF; Roballo, KC; Schwarzbach, SV; Xavier, PLP, 2019)	1.57
"The methadone dose was lower when compared with general OST treatment recommendations."	( Opioid substitution treatment in pretrial prison detention: a case study from Geneva, Switzerland. Baroudi, M; Barro, J; Broers, B; Casillas, A; Favrod-Coune, T; Gaspoz, JM; Gétaz, L; Rieder, JP; Wolff, H, 2013)	0.87
"Methadone plays an increasing role in drug-related deaths in Hamburg. "	( Intravenous methadone application as a serious risk factor for an overdose death: methadone-related fatalities in Hamburg from 2007 to 2012. Andresen-Streichert, H; Elakkary, S; Heinemann, A; Iwersen-Bergmann, S; Jungen, H; Müller, A; Püschel, K, 2014)	2.22
"Methadone caused an increase in arterial blood pressure and arterial partial pressure of carbon dioxide, while heart rate and pH decreased."	( Effects of Methadone on the Minimum Anesthetic Concentration of Isoflurane, and Its Effects on Heart Rate, Blood Pressure and Ventilation during Isoflurane Anesthesia in Hens (Gallus gallus domesticus). da Rocha, RW; Escobar, A; Pypendop, BH; Sousa, SS; Valadão, CA; Zangirolami Filho, D, 2016)	1.55
"Methadone may cause respiratory depression. "	( Mechanisms of respiratory insufficiency induced by methadone overdose in rats. Baud, FJ; Chevillard, L; Declèves, X; Mager, D; Mégarbane, B; Milan, N; Ricordel, I; Risède, P, 2010)	2.06
"Both methadone and heroin inhibit hERG currents in a concentration-dependent manner."	( Comparison of the effects of methadone and heroin on human ether-à-go-go-related gene channels. Wos-Maganga, M; Zünkler, BJ, 2010)	1.11
"Methadone overdose can cause DAL with profound disturbances of neural metabolism and the BBB. "	( Imaging of subacute blood-brain barrier disruption after methadone overdose. Gasparovic, C; Huisa, BN; Prestopnik, JL; Rosenberg, GA; Taheri, S, 2013)	2.08
"Methadone may cause respiratory depression and fatalities. "	( Respiratory effects of diazepam/methadone combination in rats: a study based on concentration/effect relationships. Baud, FJ; Chevillard, L; Declèves, X; Mégarbane, B; Risède, P, 2013)	2.12
"Methadone did not produce superior analgesic efficiency or overall tolerability at 4 weeks compared with morphine as a first-line strong opioid for the treatment of cancer pain."	( Methadone versus morphine as a first-line strong opioid for cancer pain: a randomized, double-blind study. Bertolino, M; Bosnjak, S; Bruera, E; Fisch, MJ; Mathias, C; Moyano, J; Palmer, JL; Rico, MA; Spruyt, O; Strasser, F; Sweeney, C; Willey, J, 2004)	3.21
"Methadone ingestion may cause delayed coma and require naloxone infusion. "	( Onset of symptoms after methadone overdose. D'Incognito, C; LoVecchio, F; Pizon, A; Riley, B; Sami, A, 2007)	2.09
"Methadone, because of its NMDA antagonist properties, offers an effective treatment for OIH."	( Using methadone to treat opioid-induced hyperalgesia and refractory pain. Axelrod, DJ; Reville, B, )	1.33
"Methadone use was lower among Aboriginal than among non-Aboriginal injection drug users. "	( Rate of methadone use among Aboriginal opioid injection drug users. Barney, L; Kerr, T; Li, K; Montaner, JS; Tyndall, MW; Wood, E, 2007)	2.22
"Methadone appears to cause deficits in behavioral development which can be detected at weaning."	( Methadone exposure in utero: effects on open-field activity in weanling rats. Freeman, PR, 1980)	2.43
"Methadone did not increase food intake with food available under a fixed ratio 1 (FR 1) reinforcement schedule."	( Methadone and feeding: sources of differences between home cage and operant chamber assessment procedures. Billington, CJ; Cleary, J; Levine, AS; Rudski, JM; Schaal, DW; Thompson, T, 1994)	2.45
"methadone, much lower doses than those suggested by the opioid conversion charts should be used as starting doses."	( Intravenous methadone for cancer pain unrelieved by morphine and hydromorphone: clinical observations. Borsook, D; Chandler, SW; Manfredi, PL; Payne, R, 1997)	1.4
"The methadone group was slower to process all sentences compared with family members."	( The processing of automatic thoughts of drug use and craving in opiate-dependent individuals. Feldtkeller, BT; Law, F; Myles, J; Nutt, DJ; Weinstein, AM, 2000)	0.79
"Methadone patients had lower baseline MHPG levels."	( Yohimbine-induced withdrawal and anxiety symptoms in opioid-dependent patients. Charney, DS; Kosten, TR; Krystal, JH; Petrakis, IL; Southwick, SM; Stine, SM, 2002)	1.04

Treatment

Methadone maintenance treatment (MMT) is an evidence-based effective treatment for drug addiction. There are few studies investigating depression, suicidal ideation, and their related factors among MMT users. Patients have a high prevalence of central sleep apnea and ataxic patients.

Excerpt	Reference	Relevance
"Methadone treatment of opioid use disorder in HIV-infected individuals is complicated by drug-drug interactions. "	( Effect of HIV, antiretrovirals, and genetics on methadone pharmacokinetics: Results from the methadone antiretroviral pharmacokinetics study. Bart, G; Brundage, RC; Giang, LM; Hodges, JS; Yen, H, 2021)	2.32
"Methadone maintenance treatment (MMT) is widely used for heroin use disorder. "	( The influence of methadone on cerebral gray matter and functional connectivity. Li, Q; Li, W; Li, Z; Liu, Y; Sun, Y; Wang, F; Wang, S; Wang, W; Zhu, J, 2021)	2.4
"Methadone maintenance treatment (MMT) is recognized as an effective and mainstream alternative treatment for heroin addiction. "	( Assessing brain activity in male heroin-dependent individuals under methadone maintenance treatment: A resting-state fMRI study. Chen, J; Li, Q; Li, W; Li, Z; Wang, F; Wang, S; Wang, W; Xue, J; Zhu, J, 2022)	2.4
"Methadone maintenance treatment (MMT) is considered as an effective and mainstream therapy for heroin dependence. "	( The effect of long-term methadone maintenance treatment on coupling among three large-scale brain networks in male heroin-dependent individuals: A resting-state fMRI study. Chen, J; Huang, P; Li, Q; Li, W; Li, Y; Li, Z; Liang, Z; Liu, W; Shi, H; Wang, F; Wang, S; Wang, W; Xue, J; Zhu, J, 2022)	2.47
"Methadone treatment is proven to be highly successful in preventing opioid use disorder, reducing the use of illicit drugs, and preventing overdoses."	( Improving geographic access to methadone clinics. Bonifonte, A; Garcia, E, 2022)	1.73
"Methadone treatment (MT) for opioid use disorder is only available in opioid treatment programs (OTPs) in the United States, with retention predictive of positive health outcomes. "	( Comprehensive analysis of discharge reasons from methadone outpatient treatment programs. Andraka-Christou, B; Nguyen, TD; Totaram, R, 2022)	2.42
"Methadone treatment allowed them to regain their lives from the adverse effects of opioid use disorder."	( Exploring the experiences of clients receiving opioid use disorder treatment at a methadone clinic in Kenya: a qualitative study. Kiburi, SK; Maina, G; Mwangi, J, 2022)	1.67
"Methadone treatment is the most effective evidence-based treatment for opioid use disorder (OUD), but challenges related to dosing and premature treatment dropout argue for adjunct interventions to improve outcomes. "	( Effectiveness of Conditioned Open-label Placebo With Methadone in Treatment of Opioid Use Disorder: A Randomized Clinical Trial. Belcher, AM; Billing, AS; Cole, TO; Colloca, L; Epstein, DH; Greenblatt, AD; Hoag, SW; Kaptchuk, TJ; Magder, L; Massey, E; Rotrosen, J; Wagner, M; Weintraub, E; Wickwire, EM; Wish, ED; Wooten, W, 2023)	2.6
"Methadone medication treatment for opioid use disorder appears to remain an effective intervention for reducing illicit opioid use."	( Polydrug use among patients on methadone medication treatment: Evidence from urine drug testing to inform patient safety. Dawson, E; Gordon, AJ; Passik, S; Saloner, B; Stein, BD; Whitley, P, 2023)	1.92
"Methadone Maintenance Treatment (MMT) can be associated with severe stress and mild to moderate depressive symptoms."	( The effect of multivitamins on anxiety and depression in patients undergoing methadone maintenance treatment: A double-blind randomized controlled trial. Bateni, A; Goli, R; Lagzi, N; Talebiazar, N, 2023)	1.86
"Methadone-based treatment for pregnant women with opioid use disorder is quite prevalent in the clinical environment. "	( Perturbed neurochemical and microstructural organization in a mouse model of prenatal opioid exposure: A multi-modal magnetic resonance study. Atwood, BK; Grecco, GG; Shahid, SS; Wu, YC, 2023)	2.35
"Methadone, an OUD treatment, has been shown to be effective in reducing the risk of overdose and improving overall health and quality of life."	( Dynamic changes in methadone utilisation for opioid use disorder treatment: a retrospective observational study during the COVID-19 pandemic. Fanelli, JL; Furst, JA; Jarvis, MA; Kennalley, AL; McCall, KL; Mynarski, NJ; Nichols, SD; Piper, BJ, 2023)	1.96
"The Methadone Maintenance Treatment Stigma Mechanisms Scale appears to be a reliable measure of methadone maintenance treatment stigma with robust validity in a sample of people with opioid use disorders receiving methadone maintenance treatment."	( Factor structure, internal reliability and construct validity of the Methadone Maintenance Treatment Stigma Mechanisms Scale (MMT-SMS). Copenhaver, MM; Cunningham, CO; Earnshaw, VA; Mittal, ML; Smith, LR; Wagner, K, 2020)	1.35
"Methadone maintenance treatment (MMT) has been scaled up significantly in recent years. "	( Polysubstance Use among Patients Enrolling in Methadone Maintenance Treatment Program in a Vietnam Province with Drug-Driven HIV Epidemic. Ho, CSH; Ho, RCM; Hoang, CL; Latkin, CA; Le, TA; Nguyen, CT; Pham, DTT; Quek, TTC; Tran, BX; Tran, NHT; Tran, TH; Tran, TT; Vu, GT; Vuong, QH, 2019)	2.21
"Methadone maintenance treatment (MMT) services have been used in China for treatment of heroin dependence. "	( Monitoring consumption of methadone and heroin in major Chinese cities by wastewater-based epidemiology. Bai, Y; Du, P; Hao, F; Li, X; Thai, PK; Wang, J; Xu, Z; Zhang, C; Zhang, X; Zhou, Z, 2019)	2.26
"Methadone maintenance treatment (MMT) is an important approach to address opioid dependence. "	( Effectiveness of a Psycho-Social Intervention Aimed at Reducing Attrition at Methadone Maintenance Treatment Clinics: A Propensity Score Matching Analysis. Fan, X; Gu, J; Hao, C; Hao, Y; Lau, JTF; Li, J; Xu, H; Yang, F; Zhang, X; Zhao, Y, 2019)	2.19
"Methadone maintenance treatment (MMT) has been proven to be effective in treating opioid dependence. "	( Preferences for methadone clinics among drug users in Vietnam: a comparison between public and private models. Dang, AD; Ho, CSH; Ho, RCM; Latkin, CA; Le, TA; Nguyen, CT; Nguyen, TA; Nguyen, THT; Phan, HT; Tran, BX; Vu, GT; Ying, J; Zhang, MWB, 2020)	2.35
"Methadone maintenance treatment (MMT) has been proven to be effective in improving health status and the quality of life of illicit drug users. "	( Treatment adherence amongst drug users attending public and private methadone maintenance clinics in a northern province of Vietnam. Ha, GH; Ho, CSH; Ho, RCM; Latkin, CA; Le, MQT; Le, TA; Nguyen, CT; Nguyen, LH; Pham, DTT; Pham, HQ; Pham, KTH; Tran, BX; Tran, LMH; Tran, NHT; Tran, TH; Vu, GT, 2020)	2.24
"344 methadone maintenance treatment (MMT) patients were recruited with records and measurements on methadone dose, plasma methadone concentrations, and treatment emergent symptom scales (TESS)."	( Genetic variants in NECTIN4 encoding an adhesion molecule are associated with continued opioid use. Chen, ACH; Chung, RH; Fang, CP; Kuo, HW; Liu, CC; Liu, SC; Liu, TH; Liu, YL; Tsou, HH; Wang, SC, 2020)	1.04
"Methadone maintenance treatment programs identified 3 domains related to the integration of HIV/HCV testing on-site at MMT programs: (1) payment and billing, (2) internal and external stakeholders, and (3) medical and SUD treatment coordination. "	( Addressing Barriers to On-site HIV and HCV Testing Services in Methadone Maintenance Treatment Programs in the United States: Findings From a National Multisite Qualitative Study. Behrends, CN; Frimpong, JA; Kapadia, SN; Schackman, BR, )	1.81
"Methadone maintenance treatment (MMT) is effective in decreasing opioid use or facilitating abstinence. "	( Impulsivity and craving in subjects with opioid use disorder on methadone maintenance treatment. Du, J; Jiang, H; Li, J; Mandali, A; Ren, Q; Sun, B; Voon, V; Weidacker, K; Whiteford, S; Zhang, C; Zhang, Y; Zhou, H; Zhou, Z, 2021)	2.3
"Methadone maintenance treatment might be commonly associated with lying for several causes or manipulating psychiatrists and therapists by a number of patients. "	( Reasons for Increasing Daily Methadone Maintenance Dosage among Deceptive Patients: A Qualitative Study. Kasaeiyan, R; Khosravi, M, )	1.87
"Methadone treatment attenuates acute and long-term hypersensitivity associated with neonatal pain in a rat model. "	( Methadone effectively attenuates acute and long-term consequences of neonatal repetitive procedural pain in a rat model. de Geus, TJ; Joosten, EA; Patijn, J; Tibboel, D; van den Hoogen, NJ, 2021)	3.51
"Methadone maintenance treatment (MMT) is the most common treatment for opioid-dependent pregnant women worldwide. "	( Prenatal methadone exposure impairs adolescent cognition and GABAergic neurodevelopment in a novel rat model of maternal methadone treatment. Bird, KM; Lum, JS; Millard, SJ; Newell, KA; Pallimulla, S; Wilkie, J; Wright, IM, 2021)	2.48
"Methadone maintenance treatment (MMT) in the United States, and particularly the clinic system of distribution, is often criticized as punitive, over-regulated, and misaligned to the needs of many patients. "	( A chance to do it better: Methadone maintenance treatment in the age of Covid-19. Frank, D, 2021)	2.36
"Methadone maintenance treatment is a life-saving treatment for people with opioid use disorders (OUD). "	( Take-home dosing experiences among persons receiving methadone maintenance treatment during COVID-19. Dasgupta, N; Day, E; Figgatt, MC; Salazar, Z; Vincent, L, 2021)	2.31
"Methadone maintenance treatment or buprenorphine therapy can be effective in reducing sex- and drug-related HIV risk behaviors among African, Caribbean, and Black people. "	( Effectiveness of opiate substitution treatment in reducing HIV risk behaviors among African, Caribbean, and Black people: a systematic review. Buzuayew, A; Kahan, M; Mohamud, H; Nelson, LE; Nguemo Djiometio, JB; Njoroge, I, 2021)	2.06
"Methadone maintenance treatment is reported as cost-effective in treatment of opioid use disorder. "	( Estimate cost of providing methadone maintenance treatment at a methadone clinic in Nairobi Kenya: direct costs. Kendagor, M; Kiburi, SK; Mogaka, B; Mutinda, M, 2021)	2.36
"Methadone used for treatment of OUD was associated with male hypogonadism similar to heavy heroin use. "	( Hypogonadism in opioid using males in an inner-city cohort: A cross-sectional study. Brown, TT; Dobs, AS; Wehbeh, L, )	1.57
"Methadone maintenance treatment (MMT) is reco-gnized as a reference treatment for opioid dependence. "	( Methadone overdose in patients following methadone mainte- nance treatment:A three years overview in the district of Bari (South-Italy). De Donno, A; Favia, M; Introna, F; Mita, Q; Santoiemma, I; Strisciullo, G, 2021)	3.51
"Methadone maintenance treatment (MMT) can alleviate opioid dependence. "	( Risk of motor vehicle collisions after methadone use. Chuang, HY; Guo, YL; Ho, PS; Lin, CR; Tsai, JH; Wang, PW; Wu, TN; Yang, YH, 2021)	2.33
"Methadone Maintenance Treatment (MMT) is widely recognized as one of the most effective ways of reducing risk of overdose, arrest, and transmission of blood-borne viruses like HIV and HCV among people that use opioids. "	( "It's like 'liquid handcuffs": The effects of take-home dosing policies on Methadone Maintenance Treatment (MMT) patients' lives. Curran, L; Frank, D; Guarino, H; Mateu-Gelabert, P; Perlman, DC; Walters, SM, 2021)	2.29
"Methadone maintenance treatment (MMT) remains the cornerstone for the management of opiate abuse. "	( Add-On Selective Estrogen Receptor Modulators for Methadone Maintenance Treatment. Chang, WC; Cheng, WC; Chiang, YC; Ho, IK; Huang, CL; Lane, HY; Ma, WL; Su, YT; Yang, JC, 2021)	2.32
"Methadone maintenance treatment (MMT) is the most common pharmacological treatment for opioid use disorder (OUD), and despite its documented effectiveness, a large number of patients respond poorly and experience relapse to illicit opioids."	( Association between cannabis use and methadone maintenance treatment outcomes: an investigation into sex differences. Bhatt, M; Daiter, J; Desai, D; MacKillop, J; Marsh, DC; McDermid Vaz, S; Pare, G; Plater, C; Samaan, Z; Sanger, N; Steiner, M; Thabane, L; Varenbut, M; Worster, A; Zielinski, L, 2017)	1.45
"Methadone maintenance treatment (MMT) has been proved worldwide by large bodies of research to be one of the most effective practices for illicit drug users."	( Reliability and validity of the Treatment Outcome Profile among patients attending methadone maintenance treatment programs in Kunming, China. Deng, Y; Finch, E; Li, J; Liu, X; Shen, J; Wang, M; Wolff, K, 2017)	1.4
"Methadone maintenance treatment (MMT) is the major tapering therapy for morphine addictive patients. "	( Reduced dosing and liability in methadone maintenance treatment by targeting oestrogen signal for morphine addiction. Chen, SH; Chiang, YC; Ho, IK; Ho, WJ; Huang, CL; Lane, HY; Ma, WL; Wang, RY; Yang, HT, 2017)	2.18
"Methadone Maintenance Treatment (MMT) in the United States (U.S.) has been undergoing a shift towards conceptualizing the program as recovery-based treatment. "	( "I Was Not Sick and I Didn't Need to Recover": Methadone Maintenance Treatment (MMT) as a Refuge from Criminalization. Frank, D, 2018)	2.18
"Methadone maintenance treatment (MMT) patients face unique costs associated with their healthcare expenditures. "	( Barriers to accessing and using health insurance cards among methadone maintenance treatment patients in northern Vietnam. Boggiano, VL; Latkin, CA; Le Nguyen, AT; Nguyen, CT; Nguyen, LH; Tran, BX, 2017)	2.14
"Methadone maintenance treatment (MMT) improves patients' ability to access HIV-related services and reduces needle sharing and other risky HIV-related behaviors. "	( Sexual behaviors among methadone maintenance patients in a mountainous area in northern Vietnam. Boggiano, VL; Hoang, CD; Latkin, CA; Le, HQ; Le, HT; Nguyen, CT; Nguyen, HLT; Nguyen, LH; Tran, BX; Tran, TD; Van Nguyen, H; Vu, TMT; Zary, N, 2017)	2.21
"Methadone maintenance treatment is an effective way to reduce harms associated with opioid use disorder and, in several countries, is delivered in community-based primary care settings. "	( Primary Care Physicians' Views about Prescribing Methadone to Treat Opioid Use Disorder. Adams, E; Hering, R; Jordan, M; Livingston, JD; MacMillan, Z, 2018)	2.18
"The methadone maintenance treatment (MMT) has been initiated in Wuhan, China since early 2006. "	( Social-demographic shift in drug users at the first-ever- methadone maintenance treatment in Wuhan, China. Dong, QL; Liu, C; Liu, PL; Luo, L; Wang, X; Xu, J; Zhou, W, 2017)	1.26
"A methadone maintenance treatment (MMT) program to curb the dual epidemics of HIV/AIDS and drug use has been administered by China since 2004. "	( Spatial distribution of HIV, HCV, and co-infections among drug users in the southwestern border areas of China (2004-2014): a cohort study of a national methadone maintenance treatment program. He, C; Huang, W; Lan, G; Li, C; Li, M; Li, R; Liang, N; Peng, Z; Shen, Z; Tang, X; Zhong, F, 2017)	1.37
"Methadone maintenance treatment was the primary independent variable and was treated as a time-varying exposure."	( Associations between methadone maintenance treatment and crime: a 17-year longitudinal cohort study of Canadian provincial offenders. McCandless, LC; Moniruzzaman, A; Patterson, M; Russolillo, A; Somers, JM, 2018)	1.52
"Methadone is a standard treatment for opioid dependence in pregnancy; however, its impact on maternal corrected QT interval (QTc) has not been evaluated. "	( Corrected QT Interval and Methadone Dose and Concentrations in Pregnant and Postpartum Women. Bogen, DL; Hanusa, BH; Mendelson, MA; Perel, JM; Sherman, F; Wisner, KL, )	1.87
"Methadone maintenance treatment physicians normalized most episodes as outpatients, often in collaboration with patients' primary care physicians."	( Long QTc During Methadone Maintenance: Contributors and Interventions Over 4 Years. Batres-Y-Carr, T; Thuras, P; Westermeyer, J; Yoon, G, 2017)	1.52
"Methadone treatment was developed by Drs."	( From Narcotic to Normalizer: The Misperception of Methadone Treatment and the Persistence of Prejudice and Bias. Joseph, H; Woods, JS, 2018)	1.46
"Methadone maintenance treatment (MMT) is underutilized in correctional settings, and those receiving MMT in the community often undergo withdrawal upon incarceration. "	( Feasibility and Effectiveness of Continuing Methadone Maintenance Treatment During Incarceration Compared With Forced Withdrawal. Maurer, K; McKee, SA; Moore, KE; Oberleitner, L; Smith, KMZ, )	1.84
"Methadone maintenance treatment (MMT) services may reduce the risk of HIV transmission if patients completely adhere to the treatment. "	( Social and structural barriers for adherence to methadone maintenance treatment among Vietnamese opioid dependence patients. Latkin, CA; Nguyen, LH; Tran, BX; Tran, TT, 2018)	2.18
"Methadone maintenance treatment (MMT) is an effective way to address opioid use disorder and prevent overdose; however, few jails and prisons in the United States initiate or continue people who are incarcerated on MMT."	( A randomized, open label trial of methadone continuation versus forced withdrawal in a combined US prison and jail: Findings at 12 months post-release. Brinkley-Rubinstein, L; Dauria, E; Larney, S; Macmadu, A; McKenzie, M; Rich, J; Zaller, N, 2018)	1.48
"Methadone maintenance treatment (MMT) patients are often under-nourished and overweight. "	( Knowledge about nutrition, eating habits and weight reduction intervention among methadone maintenance treatment patients. Adelson, M; Herzman-Harari, S; Peles, E; Sason, A, 2018)	2.15
"Methadone maintenance treatment center in Connecticut, USA."	( An investigation of an open-access model for scaling up methadone maintenance treatment. Ball, SA; Barry, DT; Eggert, KF; Farnum, SO; Freeman, RM; Madden, LM; Quanbeck, AR; Savage, ME; Schottenfeld, RS; Shi, JM, 2018)	2.17
"Methadone maintenance treatment (MMT) programs have expanded rapidly in China during the last decade. "	( Service providers' adherence to methadone maintenance treatment protocol in China. Lan, CW; Li, L; Lin, C; Rou, K, 2018)	2.21
"Methadone treatment (exposure) was self-reported and severe FI (outcome) was measured using the Household Food Security Survey Module."	( Methadone treatment, severe food insecurity, and HIV-HCV co-infection: A propensity score matching analysis. Cooper, C; Cox, J; Hamelin, AM; Harper, S; Klein, MB; McLinden, T; Moodie, EEM; Rossi, C; Rourke, SB; Walmsley, SL, 2018)	2.64
"Methadone maintenance treatment (MMT) is highly effective for reducing heroin use and HIV transmission among people who inject opioids. "	( Factors associated with concurrent heroin use among patients on methadone maintenance treatment in Vietnam: A 24-month retrospective analysis of a nationally representative sample. Bingham, T; Duong, H; Hoang, T; Lyss, S; Nguyen, D; Nguyen, H; Nguyen, M; Nguyen, T; Shiraishi, RW; Tran, H, 2018)	2.16
"Methadone maintenance treatment (MMT) has been shown to be an effective therapeutic strategy for opioid users. "	( Factors affecting the dose of methadone among patients receiving methadone maintenance therapy in Taiwan. Chung, KS; Hsu, CY; Li, DJ; Wu, HC; Yen, CF, 2018)	2.21
"Methadone maintenance treatment (MMT) may prevent overdose and death among homeless people with opioid dependence, but suboptimal medication adherence is a common limitation."	( The effect of Housing First on adherence to methadone maintenance treatment. Moniruzzaman, A; Parpouchi, M; Rezansoff, SN; Russolillo, A; Somers, JM, 2018)	1.46
"Methadone maintenance treatment (MMT) greatly contributed to the successful outcomes of prevention and control on both AIDS and drug abuse in China. "	( [Current situation on new psychoactive substances abuse among methadone maintenance treatment patients in China]. Cao, XB; Cheng, Z; Dai, MM, 2018)	2.16
"Methadone Maintenance Treatment (MMT) is utilized by an increasingly broad age-range of individuals with opioid use disorders. "	( Characteristics of Medicaid recipients in Methadone Maintenance Treatment: A comparison across the lifespan. Brooks, JM; Bruce, ML; Bryson, WC; Cotton, BP; Lohman, MC, 2018)	2.19
"Methadone maintenance treatment (MMT) is used to detoxify users of illicit opiates, but drug relapse is common and associated with poor quality of life (QoL)."	( Impacts of GRIN3A, GRM6 and TPH2 genetic polymorphisms on quality of life in methadone maintenance therapy population. Chen, HJ; Huang, CL; Hung, CC; Lee, HY; Lee, TE; Wang, JY; Wang, RY, 2018)	1.43
"Methadone maintenance treatment (MMT) is one of the best evidence-based opioid substitution treatments (OSTs), but there is uncertainty about whether methadone treatment reduces the risk of mortality among convicted offenders over extended follow-up periods."	( Methadone maintenance treatment and mortality in people with criminal convictions: A population-based retrospective cohort study from Canada. Moniruzzaman, A; Russolillo, A; Somers, JM, 2018)	2.64
"Methadone Maintenance Treatment (MMT) program's success depends on the likelihood of reducing drop-out rate and keeping patients remaining in the program. "	( Variation Overtime among Patients of the Six Methadone Maintenance Treatment Clinics in Thai Nguyen from 2011 to 2015. Dao, ATM; Nguyen, HTT; Nguyen, LH, 2018)	2.18
"Methadone treatment was associated with a 22% shorter median LOS (18 days [IQR, 11-30 days] vs 23 days [IQR, 16-33]; P < .001) and a 19% shorter median NICU stay (17 days [IQR, 10-29 days] vs 21 days [IQR, 14-36 days]; P < .001)."	( Morphine vs Methadone Treatment for Infants with Neonatal Abstinence Syndrome. Benjamin, DK; Bennett, MM; Clark, RH; Greenberg, RG; Murthy, K; Smith, PB; Tolia, VN, 2018)	1.58
"Methadone maintenance treatment has proven effectiveness in the treatment of opioid use disorder, but significant barriers remain to treatment retention. "	( Re-engineering methadone-Cost-effectiveness analysis of a patient-centered approach to methadone treatment. Dunlap, LJ; Gryczynski, J; Kelly, SM; Meinhofer, A; Mitchell, SG; O'Grady, KE; Orme, S; Schwartz, RP; Zarkin, GA, 2018)	2.28
"Methadone maintenance treatment (MMT) is an important treatment tool for the opioid epidemic. "	( Double jeopardy: a review of weight gain and weight management strategies for psychotropic medication prescribing during methadone maintenance treatment. Antoine, DG; Huhn, AS; Schlienz, NJ; Speed, TJ; Sweeney, MM, 2018)	2.13
"Methadone Maintenance Treatment (MMT) program has been considered a medium through which human immunodeficiency virus (HIV) risks assessment and prevention on drug use/HIV-infected population can be effectively conducted. "	( Methadone Maintenance Treatment Reduces the Vulnerability of Drug Users on HIV/AIDS in Vietnamese Remote Settings: Assessing the Changes in HIV Knowledge, Perceived Risk, and Testing Uptake after a 12-Month Follow-Up. Dam, VN; Do, HN; Do, HP; Doan, PL; Fleming, M; Ho, CS; Ho, MT; Ho, RC; Hoang, VH; Latkin, CA; Le, HT; Le, XTT; Nguyen, ALT; Nguyen, HH; Nguyen, HLT; Nguyen, LT; Nguyen, TH; Nguyen, TMT; Nguyen, V; Pham, MD; Tran, BX; Vuong, QH; Vuong, TT, 2018)	3.37
"Methadone maintenance treatment (MMT) is a harm reduction approach for persons who wish to stop using opioids and is rather effective if used for a minimum of 12 months. "	( Methadone maintenance treatment as social control: Analyzing patient experiences. Jeske Pearson, C; O'Byrne, P, 2019)	3.4
"Methadone (MET)-based treatment is currently one of the best known approaches in the treatment of opioid dependence. "	( Histopathological study of liver tissue due to methadone consumption and its effect on liver enzymes and inflammatory indices in rat. Ahmadi, MRH; Amraei, M; Azizi, M; Daemi, A; Mohamadpour, M; Omidi, M; Shirzadpour, E, 2018)	2.18
"Methadone maintenance treatment (MMT) and protracted abstinence (PA) are common methods of therapy in heroin addiction as both suppress the craving for drug use. "	( Assessing drug cue-induced brain response in heroin dependents treated by methadone maintenance and protracted abstinence measures. Chen, J; Dang, S; Li, Q; Li, W; Li, Y; Liu, J; Liu, W; Liu, Y; Shi, H; Wang, F; Wang, W; Wei, X; Xue, J; Zhu, J, 2020)	2.23
"For methadone-treated pregnancies, treatment enrollment before pregnancy and spousal methadone treatment elevated prenatal visits by 8% and 18% (0.48 and 1.08 visits, respectively)."	( Inadequate prenatal care utilization among women with and without methadone-treated opioid use disorders in Taiwan. Chang, SH; Chen, CY; Fang, SY; Huang, N; Tsay, JH; Wang, IA, 2019)	1.23
"Methadone maintenance treatment (MMT) might be associated with the symptoms of depression and anxiety, sleep disturbances and sexual dysfunctions. "	( The effects of crocin on psychological parameters in patients under methadone maintenance treatment: a randomized clinical trial. Asemi, Z; Banafshe, HR; Ghaderi, A; Khalatbari-Mohseni, A; Mirhosseini, N; Omidi, A, 2019)	2.19
"Methadone treatment was divided into medicated (methadone was dispensed) and nonmedicated (methadone was not dispensed) periods and analyzed as a time-varying exposure."	( Association of Methadone Treatment With Substance-Related Hospital Admissions Among a Population in Canada With a History of Criminal Convictions. Moniruzzaman, A; Russolillo, A; Somers, JM, 2019)	2.31
"Methadone maintenance treatment, initially introduced in Vietnam for HIV harm reduction, has marked a significant switch in the country's drug policy - from addiction as a moral issue to addiction as a brain disease. "	( Struggling to achieve a 'normal life': A qualitative study of Vietnamese methadone patients. Chauvin, C; Feelemyer, J; Jarlais, DD; Jauffret-Roustide, M; Le, MG; Luong, AN; Nagot, N; Nguyen, TT; Nham, TTT, 2019)	2.19
"Methadone maintenance treatment (MMT) requires patients to intake their daily dose in person at their clinic. "	( Factors Associated with Compliance among Methadone Maintenance Treatment Transfers: Evidence from Audit Records at Clinics in Guangdong, China. Chen, W; Gong, C; Ling, L; Liu, Y; Lu, Q; Zou, X, 2019)	2.22
"Methadone is a vital treatment for women with opioid use disorder in pregnancy. "	( Methadone, Pierre Robin sequence and other congenital anomalies: case-control study. Addor, MC; Barisic, I; Cleary, B; de Walle, HEK; Dolk, H; Gatt, M; Klungsoyr, K; Loane, M; Matias Dias, C; McDonnell, B; Neville, A; Pierini, A; Rissmann, A; Tucker, DF; Zurriaga, O, 2020)	3.44
"Methadone maintenance treatment is the gold standard of medication-based treatment for OUD, but high-dose methadone is associated with cardiotoxicity and respiratory complications, among other side effects."	( Open-label dose-extending placebos for opioid use disorder: a protocol for a randomised controlled clinical trial with methadone treatment. Belcher, AM; Billing, AS; Cole, TO; Colloca, L; Epstein, DH; Greenblatt, AD; Hamilton, KR; Hoag, SW; Kaptchuk, TJ; Kozak, ZK; Massey, E; Wagner, M; Weintraub, E; Welsh, CJ; Wickwire, EM; Wish, ED, 2019)	1.44
"Methadone maintenance treatment (MMT) programs have been used worldwide to reduce the number of drug users and for HIV prevention; however, evidence of their effectiveness in mountainous areas is limited. "	( Changes in Substance Abuse and HIV Risk Behaviors over 12-Month Methadone Maintenance Treatment among Vietnamese Patients in Mountainous Provinces. Dam, NV; Do, HN; Doan, LP; Fleming, M; Ho, CS; Ho, MT; Ho, RC; Latkin, C; Nguyen, TMT; Tran, BX; Vu, GT; Vuong, QH; Vuong, TT, 2019)	2.2
"Methadone maintenance treatment (MMT) is an effective therapy for opioid-dependence; its use is based on a harm reduction philosophy and represents one of a range of treatment approaches for opioid-dependent individuals. "	( Problem based review: The patient taking methadone. Arora, A; Williams, K, 2013)	2.1
"Methadone treatment was not found to increase the treatment requirement for neonatal abstinence syndrome compared with those using heroin only (P = 0.91)."	( Predictors of neonatal outcomes amongst a methadone- and/or heroin-dependent population referred to a multidisciplinary Perinatal and Family Drug Health Service. Buckley, V; Haber, P; Razaghi, A, 2013)	1.38
"Methadone treatment was beneficial in predicting the discharge custody status of the neonate. "	( Predictors of neonatal outcomes amongst a methadone- and/or heroin-dependent population referred to a multidisciplinary Perinatal and Family Drug Health Service. Buckley, V; Haber, P; Razaghi, A, 2013)	2.1
"The methadone maintenance treatment (MMT) program has been implemented in Shanghai since 2005. "	( Trends and predictors in methadone maintenance treatment dropout in Shanghai, China: 2005-2011. Asche, CV; Fu, J; Kirkness, CS; Ning, Z; Pan, Q; Ren, J; Ye, X; Zhuang, M, 2013)	1.25
"Methadone maintenance treatment (MMT) effectively reduces illicit opioid use and its negative consequences when patients participate in and adhere to treatment. "	( Meaning and methadone: patient perceptions of methadone dose and a model to promote adherence to maintenance treatment. Lubrano, MC; Lucan, SC; Roose, RJ; Sanders, JJ, )	1.95
"Methadone maintenance treatment (MMT) has been successfully scaled up nationally in China. "	( Effectiveness of prize-based contingency management in a methadone maintenance program in China. Chen, W; Hong, Y; Ling, L; McLaughlin, MM; Xia, Y; Zou, X, 2013)	2.08
"methadone for the treatment of opioid dependence during pregnancy suggest buprenorphine-exposed neonates had less severe NAS, but may require pharmacologic treatment for NAS later than methadone-exposed neonates."	( Time to initiation of treatment for neonatal abstinence syndrome in neonates exposed in utero to buprenorphine or methadone. Badger, GJ; Gaalema, DE; Heil, SH; Johnston, AM; Metayer, JS, 2013)	1.32
"Methadone maintenance treatment (MMT) was first introduced in Nepal in 1994."	( The trajectory of methadone maintenance treatment in Nepal. Ambekar, A; Kishore, K; Kumar, S; Pun, A; Rao, R, 2013)	1.45
"Oral methadone maintenance treatment was effective in improving the overall Quality of Life during the first three months of treatment in substance-dependent outpatients."	( Quality of life in patients on methadone maintenance treatment: a three-month assessment. Bakhshani, NM; Lashkaripour, K; Sadjadi, SA, 2012)	1.18
"Methadone maintenance treatment (MMT) in China was established in 2004. "	( Time to first treatment interruption in the Chinese methadone maintenance treatment programme. Detels, R; Sullivan, SG; Wu, Z, 2013)	2.08
"Methadone maintenance treatment (MMT) has been scaled up by the Chinese government alongside persistent compulsory drug user detention, but the extent to which detention interferes with MMT is unknown. "	( Methadone maintenance treatment participant retention and behavioural effectiveness in China: a systematic review and meta-analysis. Chow, EP; Liang, Y; Ling, L; Tang, C; Tucker, JD; Wang, Y; Wilson, DP; Zhang, L; Zhuang, X, 2013)	3.28
"Methadone maintenance treatment (MMT) is a major treatment regimen for opioid dependence."	( Hepatitis C virus infection influences the S-methadone metabolite plasma concentration. Chang, YS; Ho, IK; Hsu, YT; Kuo, HW; Liu, SW; Liu, YL; Tsou, HH; Wang, SC; Wu, SL, 2013)	1.37
"In methadone maintenance treatment programs (MMTPs), 80-90% of participants smoke cigarettes. "	( Perceived stress and substance use in methadone-maintained smokers. Anderson, BJ; Moitra, E; Stein, MD, 2013)	1.28
"Methadone maintenance treatment (MMT) was implemented in mainland China since 2004. "	( Retention in methadone maintenance treatment in mainland China, 2004-2012: a literature review. Zhou, K; Zhuang, G, 2014)	2.21
"Methadone maintenance treatment (MMT) has been available in Guangdong province, China since 2006. "	( High prevalence of HIV, HCV and tuberculosis and associated risk behaviours among new entrants of methadone maintenance treatment clinics in Guangdong Province, China. Chen, W; Ling, L; Zhang, D; Zhang, L; Zou, X, 2013)	2.05
"Methadone maintenance treatment has been subjected to much debate and controversy in Sweden during the last decades. "	( Excusing exclusion: Accounting for rule-breaking and sanctions in a Swedish methadone clinic. Petersson, FJ, 2013)	2.06
"Methadone was the treatment of preference, with a prescribed mean dose of 41.7 mg (standard deviation 29.1) upon departure."	( Opioid substitution treatment in pretrial prison detention: a case study from Geneva, Switzerland. Baroudi, M; Barro, J; Broers, B; Casillas, A; Favrod-Coune, T; Gaspoz, JM; Gétaz, L; Rieder, JP; Wolff, H, 2013)	1.11
"Methadone maintenance treatment is the most widely-used therapy in opioid dependence, but some patients relapse or drop out from treatment. "	( ALDH5A1 variability in opioid dependent patients could influence response to methadone treatment. De Cid, R; Escaramís, G; Estivill, X; Farré, M; Fonseca, F; Gratacòs, M; Martín-Santos, R; Torrens, M, 2014)	2.07
"Methadone maintenance treatment (MMT) helps individuals with an opioid use disorder abstain from or decrease use of illegal or nonmedical opiates."	( Medication-assisted treatment with methadone: assessing the evidence. Daniels, AS; Delphin-Rittmon, ME; Dougherty, RH; Fullerton, CA; Ghose, SS; Kim, M; Lyman, DR; Montejano, LB; Thomas, CP, 2014)	1.4
"Methadone treatment was switched to SROM with flexible dosing and vice versa according to period and sequence of treatment."	( Maintenance treatment for opioid dependence with slow-release oral morphine: a randomized cross-over, non-inferiority study versus methadone. Backmund, M; Beck, T; Haasen, C; Reimer, J; Ruckes, C; Schuler, C; Verthein, U; Walcher, S, 2014)	1.33
"Methadone maintenance treatment (MMT) is the standard of care during pregnancy for opioid-dependency, showing efficacy in improving prenatal care and reducing risk of relapse. "	( Rates of fetal polydrug exposures in methadone-maintained pregnancies from a high-risk population. Delano, K; Gareri, J; Koren, G, 2013)	2.11
"Methadone maintenance treatment (MMT) clinics have been implemented in China since 2004."	( Epidemiology of syphilis infection among drug users at methadone maintenance treatment clinics in China: systematic review and meta-analysis. Peng, WJ; Wan, YN; Wang, BX; Wang, J; Wang, YJ; Yan, JW; Zhang, L, 2014)	1.37
"Methadone maintenance treatment and buprenorphine maintenance treatment are the two main therapeutic options considered for opioid replacement therapy. "	( Outcome evaluation of the opioid agonist maintenance treatment in Iran. Baneshi, MR; Esmaeili, HR; Nakhaee, N; Nikravesh, MR; Ziaddinni, H, 2014)	1.85
"Methadone maintenance treatment (MMT) patients may achieve up to a 2-week privilege of methadone take-home doses (THD), which is associated with considerable responsibility. "	( Achievement of take-home dose privileges is associated with better-perceived sleep and with cognitive status among methadone maintenance treatment patients. Adelson, M; Domany, Y; Peles, E; Sason, A; Schreiber, S; Tene, O, 2014)	2.06
"Methadone treatment appears to be associated with relatively intact cognitive control in opioid dependent individuals. "	( Cognitive control in opioid dependence and methadone maintenance treatment. Chen, PC; Chen, WT; Fang, SC; Hu, S; Huang, CY; Lee, TS; Li, CS; Liao, DL; Wu, CS, 2014)	2.11
"Methadone maintenance treatment (MMT) is a key risk reduction measure for controlling HIV transmission among drug users. "	( Situation-specific factors predicting nonadherence to methadone maintenance treatment: a cross-sectional study using the case-crossover design in Guangzhou, China. Chen, L; Gu, J; Hao, C; Hao, Y; Lau, JT; Wang, Z; Xu, H, 2014)	2.09
"Methadone maintenance treatment in primary care is cost-effective and improves outcomes for opiate-dependent patients. "	( Methadone-maintained patients in primary care have higher rates of chronic disease and multimorbidity, and use health services more intensively than matched controls. Cox, AM; Darker, C; Hambly, R; O'Shea, B; O'Toole, J, 2014)	3.29
"Methadone maintenance treatment (MMT) has been used to treat opiate dependence since the mid-1960s. "	( Neuropsychological performance of methadone-maintained opiate users. Jensen, M; Kydd, R; Russell, BR; Wang, GY; Wouldes, TA, 2014)	2.12
"Methadone maintenance treatment (MMT) patients have an exceedingly high prevalence of tobacco use, and interventions that have been specifically developed for this vulnerable subpopulation have struggled to attain even modest rates of cessation. "	( Early quit days among methadone-maintained smokers in a smoking cessation trial. Anderson, BJ; Caviness, CM; de Dios, MA; Stein, MD, 2014)	2.16
"Methadone maintenance treatment is proven to be effective treatment for opioid dependence. "	( Clinical factors associated with sexual dysfunction among men in methadone maintenance treatment and buprenorphine maintenance treatment: a meta-analysis study. Hisham Hashim, HM; Loh, HS; Ng, CG; Yee, A, )	1.81
"Methadone maintenance treatment is the most widely prescribed treatment for opiate dependence with proven benefits for patients. "	( Are empty methadone bottles empty? An analytic study. Bellivier, F; Bloch, V; Bourgogne, E; Brichant-Petitjean, C; Cavalcanti, L; Dupuy, G; Gomberoff, L; Laprévote, O; Lépine, JP; Vorspan, F, 2014)	2.25
"Methadone treatment was introduced in Taiwan in 2006 as a harm-reduction program for injection drug users (IDUs), among whom HIV was endemic. "	( Prevalence and factors associated with HIV infection among injection drug users at methadone clinics in Taipei, Taiwan. Chou, P; Deng, CY; Jiang, XR; Li, LH; Lin, T; Yen, MY; Yen, YF, 2014)	2.07
"Methadone maintenance treatment (MMT) is commonly used for chronic pain control and for substitution in heroin addicts undergoing rehabilitation. "	( Treatment of methadone-induced torsades de pointes with lidocaine. Akkus, NI; Mundi, AS; Rajpal, S; Reddy, PC, )	1.94
"Methadone maintenance treatment (MMT) is safe and effective for heroin addiction, but the neural basis of the length effects of long-term MMT on brain activity during craving in former heroin addicts is unclear. "	( Reduced responses to heroin-cue-induced craving in the dorsal striatum: effects of long-term methadone maintenance treatment. Cheng, J; Gold, MS; Li, Q; Li, W; Li, Y; Wang, H; Wang, L; Wang, W; Wang, Y; Yan, X; Zhang, D; Zhu, J, 2014)	2.06
"Most methadone maintenance treatment patients are smokers, and methadone administration has been shown to increase cigarette smoking."	( Methadone is a non-competitive antagonist at the α4β2 and α3* nicotinic acetylcholine receptors and an agonist at the α7 nicotinic acetylcholine receptor. Salminen, O; Talka, R; Tuominen, RK, 2015)	2.31
"Methadone maintenance treatment patients in Wuhan, China show a high prevalence of hepatitis C virus at admission (72.1%) and a high rate of seroconversion during treatment (46.3%). "	( Hepatitis C seroconversion in methadone maintenance treatment programs in Wuhan, China. Chawarski, MC; Desrosiers, A; Liu, M; Liu, P; Luo, L; Peng, J; Schottenfeld, R; Wang, X; Xie, N; Zhou, S; Zhou, W, 2015)	2.15
"Methadone maintenance treatment (MMT) has been implemented in China since 2004 and has expanded into a nationwide programme. "	( Methadone maintenance treatment programme reduces criminal activity and improves social well-being of drug users in China: a systematic review and meta-analysis. Chow, EP; Li, T; Li, XY; Lu, YH; Sun, HM; Tian, T; Xian, Y; Zhang, L; Zhuang, X, 2015)	3.3
"Methadone maintenance treatment (MMT) has been used as a treatment for opiate dependence since the mid-1960s. "	( Quantitative EEG and Low-Resolution Electromagnetic Tomography (LORETA) Imaging of Patients Undergoing Methadone Treatment for Opiate Addiction. Kydd, RR; Russell, BR; Wang, GY, 2016)	2.09
"Methadone maintenance treatment (MMT) is widely available in China; but, high rates of illicit opiate use and dropout are problematic. "	( Efficacy of Cognitive Behavioral Therapy on Opiate Use and Retention in Methadone Maintenance Treatment in China: A Randomised Trial. Chen, H; Du, J; Jiang, H; Li, Z; Ling, W; Pan, S; Zhao, M, 2015)	2.09
"Methadone maintenance treatment (MMT) was introduced to China in 2004 to reduce the harm of injecting drug users (IDUs). "	( Illicit Heroin and Methamphetamine Use among Methadone Maintenance Treatment Patients in Dehong Prefecture of Yunnan Province, China. Bai, H; Ding, Y; Duan, S; Gao, M; He, N; Tang, R; Wang, J; Wang, R; Yang, Y; Ye, R, 2015)	2.12
"Methadone maintenance treatment programs (MMTPs) are important public health intervention to control the human immunodeficiency virus (HIV) and the drug use problems. "	( Effects of publicly funded and quality of life on attendance rate among methadone maintenance treatment patients in Taiwan: an 18-month follow-up study. Chang, KC; Lin, CY, 2015)	2.09
"Methadone maintenance treatment (MMT) reduces the harms of opioid use disorder and is being rapidly scaled-up in China. "	( Evaluation of an implementation of methadone maintenance treatment in China. Chawarski, MC; Liu, P; Marienfeld, C; Schottenfeld, R; Wang, X; Zhou, W, 2015)	2.14
"Methadone maintenance treatment facilities for managing patients with opioid addiction."	( Usefulness of the Brief Pain Inventory in Patients with Opioid Addiction Receiving Methadone Maintenance Treatment. Bawor, M; Daiter, J; Dennis, BB; Desai, D; Marsh, DC; Pare, G; Paul, J; Plater, C; Roshanov, PS; Samaan, Z; Thabane, L; Varenbut, M; Worster, A, 2016)	2.1
"Methadone maintenance treatment policy changes in British Columbia affect a structurally vulnerable population who may be less able to cope with transitions and loss of autonomy. "	( Patient perspectives of methadone formulation change in British Columbia, Canada: outcomes of a provincial survey. Amlani, A; Buxton, JA; Greer, AM; Hu, S; Moreheart, S; Sampson, O, 2016)	2.18
"Methadone maintenance treatment is characterized by large interindividual dose variability. "	( Variability of response to methadone: genome-wide DNA methylation analysis in two independent cohorts. Bellivier, F; Bloch, V; Cagnard, N; Crettol, S; Eap, C; Laplanche, JL; Lepine, JP; Marie-Claire, C; Mouly, S; Vorspan, F, 2016)	2.17
"Methadone maintenance treatment (MMT) can induce impairments in brain function and structure, despite its clinical effectiveness. "	( Methadone-induced Damage to White Matter Integrity in Methadone Maintenance Patients: A Longitudinal Self-control DTI Study. Chen, J; Li, Q; Li, W; Li, Y; Li, Z; Liu, J; Liu, Y; Wang, W; Wang, Y; Yan, X; Ye, J; Zhu, J, 2016)	3.32
"Methadone maintenance treatment (MMT) has long been used to treat heroin-dependent patients. "	( Satisfaction With Methadone Among Heroin-Dependent Patients With Current Substance Use Disorders During Methadone Maintenance Treatment. Batlle, F; Duran-Sindreu, S; Perez de Los Cobos, J; Siñol, N; Trujols, J, 2016)	2.21
"Methadone maintenance treatment (MMT) is an evidence-based effective treatment for drug addiction; however, there are few studies investigating depression, suicidal ideation, and their related factors among MMT users."	( Depression, suicidal ideation, and related factors of methadone maintenance treatment users in Guangzhou, China. Davis, A; Gu, J; Hao, C; Hao, Y; Lau, JT; Xu, H; Zhang, X; Zhao, Y, 2016)	1.4
"Methadone maintenance treatment (MMT) patients have a high prevalence of central sleep apnea and ataxic breathing related to damage to central respiratory rhythm control. "	( Respiratory Variability during Sleep in Methadone Maintenance Treatment Patients. Grunstein, RR; Kim, JW; Nguyen, CD; Thamrin, C; Wang, D, 2016)	2.14
"Methadone maintenance treatment (MMT) is commonly used for controlling opioid dependence, preventing withdrawal symptoms, and improving the quality of life of heroin-dependent patients. "	( Genome-Wide Pharmacogenomic Study on Methadone Maintenance Treatment Identifies SNP rs17180299 and Multiple Haplotypes on CYP2B6, SPON1, and GSG1L Associated with Plasma Concentrations of Methadone R- and S-enantiomers in Heroin-Dependent Patients. Chu, SK; Ho, IK; Huang, CL; Kuo, HW; Liu, SW; Liu, YL; Wang, SC; Yang, HC, 2016)	2.15
"Methadone maintenance treatment (MMT) reduces HIV risk behaviors and improves access to HIV-related services among drug users. "	( Methadone Maintenance Treatment Promotes Referral and Uptake of HIV Testing and Counselling Services amongst Drug Users and Their Partners. Latkin, CA; Nguyen, CT; Nguyen, LH; Nguyen, LP; Phan, HT; Tran, BX, 2016)	3.32
"Methadone treatment decreased slightly in all social areas until 2011 and then increased bringing rates back to 2004 levels."	( Buprenorphine and methadone treatment for opioid dependence by income, ethnicity and race of neighborhoods in New York City. DiRocco, D; Hansen, H; Siegel, C; Wanderling, J, 2016)	1.49
"Methadone maintenance treatment (MMT) is recognized as one of the most effective treatments for heroin addiction but its effect is dimmed by the high incidence of heroin relapse. "	( Regional homogeneity changes between heroin relapse and non-relapse patients under methadone maintenance treatment: a resting-state fMRI study. Chang, H; Chen, J; Li, Q; Li, W; Li, Y; Li, Z; Liu, J; Shi, M; Wang, W; Wang, Y; Ye, J; Zhu, J, 2016)	2.1
"Methadone maintenance treatment versus social services department personnel were older (42.7 ± 12.8 versus 37.5 ± 8.2 years; p = 0.03), with fewer females (48 versus 75%; p = 0.006), and 50% were social workers compared to 100% social workers in the SSD group (p < 0.0005)."	( Knowledge and stigma regarding methadone maintenance treatment among personnel of methadone maintenance treatment and non-methadone maintenance treatment addiction facilities in Israel. Adelson, M; Peles, E; Shidlansik, L, )	1.14
"Two methadone treatment programs (MTPs) in Baltimore, MD, USA."	( Patient-centered methadone treatment: a randomized clinical trial. Gandhi, D; Gryczynski, J; Jaffe, JH; Kelly, SM; Mitchell, SG; O'Grady, KE; Olsen, Y; Schwartz, RP, 2017)	1.35
"Methadone treatment, bruxism, and temporomandibular disorders among male prisoners. "	( Methadone maintenance treatment may be associated with bruxism in male prisoners. Manfredini, D, 2016)	3.32
"In methadone-treated OD subjects drawn from a case and control sample, we conducted a genome-wide association study of usual daily methadone dose."	( Genome-wide association study of therapeutic opioid dosing identifies a novel locus upstream of OPRM1. Cook-Sather, SD; Farrer, LA; Gelernter, J; Hakonarson, H; Jensen, KP; Kranzler, HR; Li, J; Nunez, Y; Smith, AH, 2017)	0.97
"Methadone maintenance treatment (MMT) of opiate addiction was introduced in Sweden 50years ago. "	( Mortality related to methadone maintenance treatment in Stockholm, Sweden, during 2006-2013. Ledberg, A, 2017)	2.22
"Methadone maintenance treatment (MMT) is the gold standard for pregnant women with opioid use disorders. "	( Newborn birth-weight of pregnant women on methadone or buprenorphine maintenance treatment: A national contingency management approach trial. Adelson, M; Peles, E; Sason, A; Schreiber, S, 2017)	2.16
"Methadone has higher treatment retention rates than buprenorphine-naloxone does, while buprenorphine-naloxone has a lower risk of overdose."	( Primary care management of opioid use disorders: Abstinence, methadone, or buprenorphine-naloxone? Kahan, M; Nader, M; Srivastava, A, 2017)	1.42
"Methadone maintenance treatment (MMT) has been shown to dramatically reduce illicit opioid use and criminal activity among injection drug users (IDU). "	( Effect of methadone treatment on incarceration rates among injection drug users. Kerr, T; Li, K; Marsh, D; Montaner, J; Werb, D; Wood, E, 2008)	2.19
"Methadone maintained treatment (MMT) patients may be given less opioid analgesia for acute pain than the general patient, due to requests for analgesia being misinterpreted as craving for drugs. "	( Management of acute pain in methadone maintenance therapy in-patients. Curry, K; Fong, D; Hines, S; Theodorou, S; Williamson, A, 2008)	2.08
"Most methadone-treated patients develop QTc prolongation."	( Heterogeneous impact of methadone on the QTc interval: what are the practical implications? Krantz, MJ, 2008)	1.11
"Methadone maintenance treatment and compulsory detoxification might he benefit to quality of life for drug addicts, and MMT contribute to it much more. "	( [Comparison of quality of life for drug addicts in methadone maintenance treatment clinics, community and compulsory detoxification institutions in Sichuan Province]. Chen, J; Wang, Y; Wu, Z; Xiao, L, 2009)	2.05
"Methadone maintenance treatment reduces rates of premature mortality in heroin addicts. "	( Benefits of retention in methadone maintenance and chronic medical conditions as risk factors for premature death among older heroin addicts. Amar, R; Casarella, J; Drexler, K; Fareed, A; Vayalapalli, S, 2009)	2.1
"VHA methadone treatment costs were higher than reported by other providers."	( Comparison of costs and utilization among buprenorphine and methadone patients. Barnett, PG, 2009)	1.08
"Methadone maintenance treatment (MMT) is typically provided separately from medical care."	( Are opioid dependence and methadone maintenance treatment (MMT) documented in the medical record? A patient safety issue. Alford, DP; Cheng, DM; Farrar, D; Samet, JH; Walley, AY, 2009)	1.37
"Methadone only treated rats had a mean paw withdrawal latency significantly lower than the corresponding values for saline on days 8, 9, 10, 11, 12, 14, and 17 (P<0.05)."	( Model of methadone-induced hyperalgesia in rats and effect of memantine. Hay, JL; Irvine, R; Kaboutari, J; Salem, A; White, JM, 2010)	1.5
"Methadone maintenance treatment (MMT) in primary care settings is used increasingly as a standard method of delivering treatment for heroin users. "	( The effect of time spent in treatment and dropout status on rates of convictions, cautions and imprisonment over 5 years in a primary care-led methadone maintenance service. Ewins, E; Griffiths, L; Keen, J; Mathers, N; Oliver, P; Rowse, G, 2010)	2
"Methadone maintenance treatment (MMT) is the most widely available pharmacotherapy for opioid addiction and has been shown to be an effective and safe treatment over a period of 40 years. "	( Pharmacotherapy in the treatment of addiction: methadone. Borg, L; Ducat, E; Kreek, MJ; Ray, B, 2010)	2.06
"Methadone maintenance treatment has been shown to reduce heroin use, criminality and mortality."	( Naltrexone implants compared to methadone: outcomes six months after prison release. Gossop, M; Katevoll, T; Kunøe, N; Lobmaier, PP; Waal, H, 2010)	1.37
"New methadone treatment admissions (N = 283) were assessed at 3 months post-admission for satisfaction with their counselors and programs. "	( The role of patient satisfaction in methadone treatment. Brown, BS; Kelly, SM; Mitchell, SG; O'Grady, KE; Schwartz, RP, 2010)	1.19
"The methadone maintenance treatment has significantly improved physical, psychological, and environmental components of quality of life during follow-up."	( Cost-utility analysis of methadone maintenance treatment in Lithuania. Bagdonas, E; Padaiga, Z; Vanagas, G, 2010)	1.14
"Methadone maintenance treatment program was less effective in terms of cost per QALY."	( Cost-utility analysis of methadone maintenance treatment in Lithuania. Bagdonas, E; Padaiga, Z; Vanagas, G, 2010)	1.39
"Methadone maintenance treatment has definite advantages for the mother and is currently recommended in the UK."	( The management of heroin misuse in pregnancy: time for a rethink? Mactier, H, 2011)	1.09
"Methadone treatment programmes present a need and an opportunity to assess and intervene in nicotine dependence and depression and in addressing and eliminating health disparities."	( Nicotine dependence and depression among women smokers on methadone maintenance. Arnold, S; Gandhi, D; Joshi, A; Khanna, N; Sadaphal, S; Stewart, D, 2010)	1.33
"Methadone treatment is a well-recognised cause of QT interval lengthening in adults."	( Maternal methadone therapy increases QTc interval in newborn infants. Bhoyar, A; Ewer, AK; Holder, G; Hussain, T; Parikh, R, 2011)	1.51
"Methadone maintenance treatment program patients were referred, evaluated by the internist and hepatologist in hepatitis clinic and provided HCV treatment with integration between both sites."	( Integrated internist - addiction medicine - hepatology model for hepatitis C management for individuals on methadone maintenance. Beeder, AB; Dimova, R; Kreek, MJ; Marks, KM; Martinez, AD; Talal, AH; Zeremski, M, 2012)	1.31
"Methadone maintenance treatment (MMT) might cause the impairments of neuropsychological and neurotransmitter function in opioid addicts. "	( White matter impairment in heroin addicts undergoing methadone maintenance treatment and prolonged abstinence: a preliminary DTI study. Li, Q; Li, W; Wang, W; Wang, Y; Yang, W; Zhu, J, 2011)	2.06
"Methadone treatment was introduced in Taiwan in 2006 as a harm-reduction program in response to the human immunodeficiency virus (HIV), which is endemic among Taiwanese heroin users. "	( Clinical characteristics and risk behavior as a function of HIV status among heroin users enrolled in methadone treatment in northern Taiwan. Chou, YC; Chuang, P; Huang, CW; Lee, TS; Liu, YL; Shen, HC; Shih, CY; Wang, BE; Wu, WH; Yen, MY, 2011)	2.03
"Methadone maintenance treatment has been made available in China in response to the rapid spread of human immunodeficiency virus (HIV), but high rates of dropout and relapse are problematic. "	( Effects of a randomized contingency management intervention on opiate abstinence and retention in methadone maintenance treatment in China. Chang, YJ; Du, J; Evans, E; Hser, YI; Huang, D; Jiang, H; Li, J; Peng, C; Roll, J; Stitzer, ML; Wu, F; Zhang, B; Zhang, C; Zhang, R; Zhao, M, 2011)	2.03
"Methadone maintenance treatment (MMT) is the standard treatment of choice for pregnant opiate addicts; however, data on newborn outcomes are contradictory. "	( Duration of methadone maintenance treatment during pregnancy and pregnancy outcome parameters in women with opiate addiction. Adelson, M; Bloch, M; Dollberg, S; Peles, E; Schreiber, S, 2012)	2.2
"methadone-treated patients."	( Cognitive functioning in opioid-dependent patients treated with buprenorphine, methadone, and other psychoactive medications: stability and correlates. Alho, H; Fabritius, C; Kalska, H; Rapeli, P, 2011)	1.32
"Methadone maintenance treatment (MMT) is efficacious in reducing drug use that may improve HIV/AIDS care and treatment outcomes. "	( Cost-effectiveness of methadone maintenance treatment for HIV-positive drug users in Vietnam. Do, NT; Duong, AT; Houston, S; Jacobs, P; Mills, S; Nguyen, LT; Ohinmaa, A; Tran, BX, 2012)	2.14
"Methadone-treated women had lower BMI, consumed more calories, had lower serum carotenoid concentrations, and higher plasma homocysteine concentrations than controls."	( A pilot study of the nutritional status of opiate-using pregnant women on methadone maintenance therapy. Bodnar, LM; Bogen, DL; Hanusa, BH; Tomedi, LE; Wisner, KL, 2012)	1.33
"Methadone maintenance treatment (MMT) is an intervention used to treat opioid (heroin) dependence. "	( Methadone as social control: institutionalized stigma and the prospect of recovery. Harris, J; McElrath, K, 2012)	3.26
"The methadone maintenance treatment (MMT) program is scaling up in China, but little is known about drug users' cognitions of MMT. "	( Misconceptions toward methadone maintenance treatment (MMT) and associated factors among new MMT users in Guangzhou, China. Fan, L; Gu, J; Hao, C; He, W; Lau, JT; Ling, W; Xu, H; Zhao, Y; Zhong, Y, 2012)	1.25
"Methadone treatment centers, in contrast to convenience stores, are not associated geographically with crime."	( Use of a 'microecological technique' to study crime incidents around methadone maintenance treatment centers. Boyd, SJ; Dixon, LB; Fang, LJ; Gorelick, DA; Medoff, DR, 2012)	2.06
"Methadone maintenance treatment is a chronic treatment for opiate addicts. "	( Long waiting period to enter methadone maintenance treatment: relation to patient characteristics and outcome. Adelson, M; Peles, E; Sason, A; Schreiber, S, 2012)	2.11
"The Methadone Maintenance Treatment Outcome Study was an 18-month prospective study from March 2007 to July 2008. "	( Self-efficacy and HIV risk behaviors among heroin users in Taiwan. Chung, KS; Hsu, ST; Ko, NY; Wang, PW; Wu, HC; Yeh, YC; Yen, CF; Yen, CN, 2012)	0.94
"Methadone maintenance treatment (MMT) has elevated rates of co-morbid memory deficit and depression that are associated with higher relapse rates for substance abuse. "	( White matter abnormalities correlating with memory and depression in heroin users under methadone maintenance treatment. Chen, CC; Chen, HL; Cheng, YF; Chou, KH; Huang, CC; Li, SH; Lin, CP; Lin, WC; Lu, CH; Wang, YL, 2012)	2.04
"Methadone maintenance treatment should not necessarily be maintained all life long and can be stopped within its prescription setting, including medical, psychological and social evaluation."	( [When and how to detoxify clients from methadone maintenance treatment?]. Bloch, V; Dugarin, J; Dupuy, G; Ksouda, K; Laqueille, X; Lépine, JP; Vorspan, F, 2013)	2.1
"366 methadone maintenance treatment patients in Taiwan were recruited and genotyped."	( UGT2B7 genetic polymorphisms are associated with the withdrawal symptoms in methadone maintenance patients. Chen, ACh; Chen, CH; Chen, YT; Fang, CP; Ho, IK; Hsiao, CF; Hsu, YT; Huang, CL; Kuo, HW; Lin, L; Liu, CT; Liu, ML; Liu, SC; Liu, YL; Shih, YH; Su, LW; Tan, HK; Tian, JN; Tsou, HH; Wu, CS; Yang, YH; Yang, YT, 2012)	1.09
"Methadone maintenance treatment (MMT) was implemented in China since 2004. "	( HIV and HCV prevalence among entrants to methadone maintenance treatment clinics in China: a systematic review and meta-analysis. Chow, EP; Liang, Y; Wang, Y; Wilson, DP; Zhang, L; Zhuang, X, 2012)	2.09
"Methadone maintenance treatment (MMT) has rapidly expanded in China, from 8 pilot sites to 696 clinics covering 27 provinces, during 2004-2010. "	( Risk factors associated with HIV/HCV infection among entrants in methadone maintenance treatment clinics in China: a systematic review and meta-analysis. Chow, EP; Liang, Y; Wang, Y; Wilson, DP; Zhang, L; Zhuang, X, 2012)	2.06
"In methadone treated cats there was no significant variation in MNT over time, suggesting a possible anti-hyperalgesic action, whereas in the other two groups lower thresholds were recorded at various time points after surgery compared to baseline."	( Methadone in combination with acepromazine as premedication prior to neutering in the cat. Bortolami, E; Murrell, JC; Slingsby, LS, 2013)	2.35
"Methadone treatment by the primary care physician is a successful method of retaining opioid users in treatment."	( A national study of the retention of Irish opiate users in methadone substitution treatment. Barry, J; Delargy, I; Grogan, L; Keenan, E; Long, J; Mulholland, D; Mullen, L, 2012)	1.34
"Methadone treatment is seen by some as in competition with their main task of coordinating conventional drug treatment in the rehabilitation center.The history of drug use and the evolution of discourses on drug use in Viet Nam have created these conflicting pressures on police, and thus created contradictory expectations and led to different views and attitudes of police regarding various harm reduction measures."	( Harm reduction and "clean" community: can Viet Nam have both? Bui, TH; Crofts, N; Jardine, M; Khuat, TH; Moore, T; Nguyen, VA, 2012)	1.1
"Methadone maintenance treatment (MMT) has become an important modality of substitution treatment for opioid addicts in China since 2006. "	( Sexual dysfunction during methadone maintenance treatment and its influence on patient's life and treatment: a qualitative study in South China. Chen, J; Chen, W; He, Q; Hu, P; Jahn, HJ; Li, X; Ling, L; Xia, Y; Zhang, D, 2013)	2.13
"Methadone maintenance treatment is evidenced as a successful harm reduction initiative in regard to the prevention of blood borne viruses and other injecting related harms. "	( Methadone diversion as a protective strategy: the harm reduction potential of 'generous constraints'. Harris, M; Rhodes, T, 2013)	3.28
"Methadone treatment has been 'programmatic', with a one-size-fits-all approach that in part reflects the perceived need to impose discipline on deviant individuals."	( Pharmacological maintenance treatments of opiate addiction. Bell, J, 2014)	1.12
"Methadone treatment non-responders, defined by a positive urine morphine test, had a higher plasma concentration of cotinine (P = 0.005), but a lower plasma concentration-to-dose ratio of both R- and S-methadone (P = 0.001 and 0.012, respectively) than the responders."	( OPRM1 genetic polymorphisms are associated with the plasma nicotine metabolite cotinine concentration in methadone maintenance patients: a cross sectional study. Chang, YS; Chen, ACh; Chen, CH; Chen, YT; Fang, CP; Ho, IK; Hsiao, CF; Kuo, HW; Lin, KM; Liu, YL; Tsai-Wu, JJ; Tsou, HH; Wang, SC; Wu, HY, 2013)	1.33
"Methadone maintenance treatment programs in the United States and a pain management center in Canada."	( Torsade de pointes associated with very-high-dose methadone. Hays, H; Krantz, MJ; Lewkowiez, L; Mehler, PS; Robertson, AD; Woodroffe, MA, 2002)	2.01
"17 methadone-treated patients who developed torsade de pointes."	( Torsade de pointes associated with very-high-dose methadone. Hays, H; Krantz, MJ; Lewkowiez, L; Mehler, PS; Robertson, AD; Woodroffe, MA, 2002)	1.19
"Methadone maintenance treatments (MMTs) are the commonest substitution treatments offered to opiate addiction in Switzerland, in order to reduce criminal behaviour, infectious disease transmission and overdose death."	( Methadone maintenance treatment, criminality and overdose-related deaths. An ecological study, 1983-1999. La Harpe, R; Niveau, G; Rougemont, AL, 2002)	3.2
"Methadone maintenance treatment is the most prominent form of pharmacotherapy treatment for illicit opiate dependence in several countries, and its application varies internationally with respect to treatment regulations and delivery modes."	( Heroin-assisted treatment as a response to the public health problem of opiate dependence. Casas, M; Fischer, B; Hall, W; Kirst, M; Krausz, M; Metrebian, N; Reggers, J; Rehm, J; Uchtenhagen, A; van den Brink, W; van Ree, JM, 2002)	1.04
"Methadone maintenance treatment (MMT) has been evaluated in the United States and in a few other countries. "	( [The impact of substitution treatment by methadone among opiate-dependent subjects evaluated by Addiction Severity Index and by urine tests]. Darreye, A; Greth, P; Kempf, M; Khidichian, F; Macher, JP; Schneider, JL; Stépien, S; Trémeau, F; Wantz, C; Weber, B; Weibel, H, )	1.84
"In methadone maintenance treatment, prognostic studies have failed to find robust predictors on the basis of single predictive variables."	( A staging system to predict prognosis among methadone maintenance patients, based on admission characteristics. Favrat, B; O'Connor, PG; Rao, S; Schottenfeld, R, 2002)	1.09
"Methadone maintenance treatment reduces drug-related-harm. "	( [Prevalence of infection by HIV and hepatitis C virus in a cohort of patients on methadone treatment]. Aragonés, A; Barril, J; Esteban, J; Gimeno, C; Pellín, Mde L, 2003)	1.99
"Methadone maintenance treatment (MMT) is a long term opioid replacement therapy, recognised as effective in the management of opioid dependence. "	( Methadone maintenance at different dosages for opioid dependence. Faggiano, F; Lemma, P; Versino, E; Vigna-Taglianti, F, 2003)	3.2
"Methadone maintenance treatment restores altered bone turnover only."	( [Bone metabolism in individuals dependent on heroin and after methadone administration]. Stĕpán, J; Wilczek, H, 2003)	1.28
"Methadone used for the treatment of maternal pain resulted in a low incidence of neonatal abstinence syndrome. "	( Outcomes of infants born to mothers receiving methadone for pain management in pregnancy. Kuschel, C; Sharpe, C, 2004)	2.02
"Methadone maintenance treatment is complicated by the wide variability of efficacy among patients. "	( Brain penetration of methadone (R)- and (S)-enantiomers is greatly increased by P-glycoprotein deficiency in the blood-brain barrier of Abcb1a gene knockout mice. DeVane, CL; Donovan, JL; Markowitz, JS; Ruan, Y; Taylor, RM; Wang, JS, 2004)	2.09
"Methadone treatment services should incorporate both primary care and psychiatric care into their programs, or at the very least secure appropriate referral mechanisms to ancillary services to ensure that the health concerns of opiate users are dealt with in the context of their treatment program."	( Self-perceived health among Canadian opiate users: a comparison to the general population and to other chronic disease populations. Challacombe, L; Fischer, B; Hopkins, S; Millson, PE; Myers, T; Pearson, M; Raftis, S; Shore, R; Strike, CJ; Villeneuve, PJ, )	1.57
"Methadone treatment for heroin addiction has been available for 40 years, but there is relatively little research on the effectiveness of Canadian programs. "	( Client retention in the British Columbia Methadone Program, 1996-1999. Anderson, JF; Warren, LD, )	1.84
"Methadone-maintenance treatment clinics are strategically appealing sites for provision of directly administered antiretroviral therapy (DAART) to human immunodeficiency virus type 1 (HIV-1)-infected injection drug users (IDUs). "	( Directly administered antiretroviral therapy in an urban methadone maintenance clinic: a nonrandomized comparative study. Hader, S; Lucas, GM; Moore, RD; Weidle, PJ, 2004)	2.01
"Methadone treatment has been shown to be an effective intervention that can lower the risk of heroin-induced overdose death. "	( Overdose deaths attributed to methadone and heroin in New York City, 1990-1998. Bryant, WK; Galea, S; Markham Piper, T; Tardiff, KJ; Tracy, M; Vlahov, D, 2004)	2.05
"All methadone maintenance treatment starting between January 1, 1997 and December 31, 1999."	( [Is methadone maintenance provided by private practitioners effective?]. Dürsteler-MacFarland, KM; Falcato, L; Nordt, C; Rössler, W; Stohler, R, 2004)	1.36
"Methadone maintenance treatment (MMT) has been the 'gold standard' pharmacotherapy treatment for illicit opioid dependence for over 30 years. "	( Eyes wide shut?--A conceptual and empirical critique of methadone maintenance treatment. Fischer, B; Kim, G; Kirst, M; Rehm, J, 2005)	2.02
"Methadone-assisted treatment was approved in Norway in 1998, buprenorphine in 2000."	( [Buprenorphine and methadone to opiate addicts--a randomized trial]. Asland, R; Espegren, O; Jakobsen, E; Kristensen, Ø; Lie, Ø; Seiler, S, 2005)	1.38
"Methadone-treated subjects remained in treatment significantly longer and achieved significantly longer periods of sustained abstinence and a greater proportion drug-free tests, compared with subjects who received buprenorphine. "	( Methadone versus buprenorphine with contingency management or performance feedback for cocaine and opioid dependence. Carroll, KM; Chawarski, MC; Kosten, TR; Pakes, JR; Pantalon, MV; Schottenfeld, RS, 2005)	3.21
"Methadone is effective treatment for opioid addiction, but regulations restrict its use. "	( Methadone medical maintenance in primary care. An implementation evaluation. Awan, A; Brumback, LC; Carney, M; Donovan, D; Jackson, TR; Kapitan, S; Merrill, JO; Saxon, AJ; Schulman, BA, 2005)	3.21
"Methadone pretreatment induced up-regulation of epibatidine binding sites in SH-SY5Y cells."	( Methadone increases intracellular calcium in SH-SY5Y and SH-EP1-halpha7 cells by activating neuronal nicotinic acetylcholine receptors. Ahtee, L; Korpi, ER; Kylänlahti, I; Lukas, RJ; Möykkynen, T; Nousiainen, H; Pakkanen, JS; Peng, JH; Tuominen, RK; Yli-Kauhaluoma, J, 2005)	2.49
"Methadone maintenance treatment of opiate addiction is highly effective at reducing drug use, drug-related criminal activity, and risk of HIV transmission."	( Linkage with methadone treatment upon release from incarceration: a promising opportunity. Clarke, J; Key, RG; McKenzie, M; Poshkus, M; Rich, JD; Shield, DC; Wolf, FA, 2005)	1.42
"Methadone maintenance treatment facility."	( Effects of methadone on QT-interval dispersion. Arnsten, JH; Gourevitch, MN; Krantz, MJ; Lowery, CM; Martell, BA, 2005)	2.16
"Methadone maintenance treatment is associated with statistically significant reductions in injecting use and sharing of injecting equipment."	( Brief report: Methadone treatment of injecting opioid users for prevention of HIV infection. Ali, RL; Bornemann, R; Farrell, M; Gowing, LR; Sullivan, LE, 2006)	1.42
"Methadone maintenance treatment for injecting drug users significantly reduces the risk of transmission of HIV and should be provided as a component of a strategic approach to the prevention and control of HIV infection. "	( Brief report: Methadone treatment of injecting opioid users for prevention of HIV infection. Ali, RL; Bornemann, R; Farrell, M; Gowing, LR; Sullivan, LE, 2006)	2.14
"A methadone treatment program in Baltimore."	( A randomized controlled trial of interim methadone maintenance. Battjes, RJ; Brady, JV; Butler, CB; Callaman, JM; Highfield, DA; Jaffe, JH; O'Grady, KE; Rouse, CO; Schwartz, RP, 2006)	1.32
"Methadone treatment was also independently associated with reduced lumbar spine BMD."	( HIV infection and bone mineral density in middle-aged women. Arnsten, JH; Floris-Moore, M; Freeman, R; Howard, AA; Santoro, N; Schoenbaum, EE, 2006)	1.06
"Five methadone maintenance treatment centers in Rhode Island."	( A smoking cessation intervention for the methadone-maintained. Anderson, BJ; Anthony, JL; Herman, DS; Niaura, R; Stein, MD; Weinstock, MC, 2006)	1.11
"Methadone maintenance treatment (MMT) has not been officially approved by the Chinese government for widespread implementation, but some pilot studies are currently underway."	( Opiate addiction in China: current situation and treatments. Cubells, JF; Tang, YL; Zhao, C; Zhao, D, 2006)	1.06
"Five methadone maintenance treatment centers."	( Nicotine replacement therapy: patterns of use after a quit attempt among methadone-maintained smokers. Anderson, BJ; Niaura, R; Stein, MD, 2006)	1.08
"Methadone treatment for heroin addiction in the UK, the 'British system', is unique as it is largely provided by General Practitioners."	( Association between availability of heroin and methadone and fatal poisoning in England and Wales 1993-2004. Griffiths, C; Hickman, M; Morgan, O, 2006)	1.31
"For methadone treatment we calculated the death rate per 1000 patient years."	( Association between availability of heroin and methadone and fatal poisoning in England and Wales 1993-2004. Griffiths, C; Hickman, M; Morgan, O, 2006)	1.07
"Methadone maintenance treatment (MMT) is a safe pharmacological treatment strategy for addiction to heroin and other opiates; however, linking individuals to MMT is often challenging. "	( Linkage to methadone treatment from acute opiate detoxification treatment. Brett, J; Carleton, JC; Rich, JD; Thurmond, P; Zaller, ND, )	1.96
"Methadone maintenance treatment (MMT) in Norway emphasizes rehabilitation and control with strict intake criteria and rules for involuntary termination. "	( Merits and problems in high-threshold methadone maintenance treatment. Evaluation of medication-assisted rehabilitation in Norway 1998-2004. Waal, H, 2007)	2.05
"Methadone maintenance treatment (MMT) for opioid dependency has consistently shown important heath, social and legal benefits. "	( Methadone death, dosage and torsade de pointes: risk-benefit policy implications. Latowsky, M, 2006)	3.22
"Methadone treatment is a well recognised cause of QT interval lengthening in adults. "	( Maternal methadone may cause arrhythmias in neonates. Ewer, AK; Hussain, T, 2007)	2.2
"Methadone maintenance treatment substantially reduces morbidity associated with opioid dependence and improves the quality of life of patients."	( Outpatient methadone maintenance treatment program. Quality of life and health of opioid-dependent persons in Lithuania. Padaiga, Z; Subata, E; Vanagas, G, 2007)	2.17
"Methadone maintenance treatment programs (MMTP) often provide onsite primary care. "	( Primary care affiliations of adults in a methadone program with onsite care. Arnsten, JH; Federman, AD, 2007)	2.05
"Methadone-treated patients, as a group, had significantly slower simple reaction time (RT) compared to buprenorphine/naloxone-treated patients. "	( Methadone vs. buprenorphine/naloxone during early opioid substitution treatment: a naturalistic comparison of cognitive performance relative to healthy controls. Alho, H; Fabritius, C; Kalska, H; Rapeli, P; Salaspuro, M; Wahlbeck, K, 2007)	3.23
"Methadone maintenance treatment is a widely used therapy in the rehabilitation of opioid addiction the world over. "	( Relationship between methadone and EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine) in urine samples from Norwegian prisons. Bernard, JP; Karinen, R; Khiabani, HZ; Mørland, J; Opdal, MS, 2007)	2.1
"Methadone treatment in chronic pain patients is still limited owing to misconceptions about addiction, safety, and its unique pharmacokinetic and pharmacodynamic properties. "	( Nurse case management program of chronic pain patients treated with methadone. Lamb, L; Pereira, JX; Shir, Y, 2007)	2.02
"The methadone maintenance treatment (MMT) program has run for more than 20 years and the public has become more tolerant of addicts."	( Comparison of drug abuse in Germany and China. Fang, YX; Lu, L; Michels, II; Zhao, D; Zhao, LY, 2007)	0.82
"Methadone maintenance treatment clinic."	( Melatonin for perceived sleep disturbances associated with benzodiazepine withdrawal among patients in methadone maintenance treatment: a double-blind randomized clinical trial. Adelson, M; Bar-Hamburger, R; Hetzroni, T; Peles, E; Schreiber, S, 2007)	2
"Methadone-treated men had lower TT than buprenorphine-treated men and reference groups."	( Hypogonadism in men receiving methadone and buprenorphine maintenance treatment. Agho, K; Attia, J; Byrne, A; Hallinan, R; McMahon, CG; Tynan, P, 2009)	1.36
"Methadone maintenance treatment (MMT) was first piloted in April 2004 in Yunnan, China, to reduce HIV transmission. "	( Societal perception and support for methadone maintenance treatment in a Chinese province with high HIV prevalence. Cheng, W; Dai, F; Li, H; Li, J; Qi, G; Ren, Z; Yang, L; Zhang, W; Zhang, Y, 2008)	2.06
"Methadone-treated women had a high degree of compliance with antepartum care, and 80% continued in the role of parent through the first year."	( Follow-up of methadone-treated and untreated narcotic-dependent women and their infants: health, developmental, and social implications. Desmond, MM; Wait, RB; Wilson, GS, 1981)	1.35
"Methadone pretreatment resulted in a dose-related increase in the number of cigarettes smoked per session (from a mean of 2.8 after placebo to 5.6 after the high dose of methadone)."	( Effects of methadone on human cigarette smoking and subjective ratings. Chait, LD; Griffiths, RR, 1984)	1.38
"Methadone Transition Treatment (MTT) is an innovative treatment organized around this strategy."	( Methadone transition treatment: a treatment model for 180-day methadone detoxification. Banys, P; Krumenaker, CL; Reilly, PM; Sees, KL; Shopshire, MS; Tusel, DJ, 1995)	2.46
"Methadone maintenance treatment programs have been shown to decrease criminal behavior, improve psychosocial functioning, and decrease injecting narcotic use, thus reducing the spread of AIDS."	( Methadone maintenance treatment. When and how to refer patients. DeMaria, PA; Weinstein, SP, 1995)	2.46
"Methadone treated offspring were no different from the controls on either measure."	( Prenatal administration of methadone in the rat: acoustic startle amplitude and the rest-activity cycle at 30 days of age. Brake, SC; Hamowy, AS; Hutchings, DE; Liu, PY; Zmitrovich, AC, )	1.15
"Methadone maintenance treatment was introduced in Austria in 1987. "	( [Methadone substitution treatment. Results of an evaluation of 3 years implementation in an Austrian province]. Rittmannsberger, H; Ruschak, M; Silberbauer, C, 1994)	2.64
"Methadone Transition Treatment (MTT) is a treatment program for opioid-addicted individuals that takes advantage of a 1989 change in federal guidelines permitting the establishment of 180-day detoxification programs. "	( Low (40 mg) versus high (80 mg) dose methadone in a 180-day heroin detoxification program. Banys, P; Delucchi, KL; Reilly, PM; Sees, KL; Tusel, DJ, )	1.85
"Methadone maintenance treatment has allowed for stabilization and normalization in the lives of hundreds of thousands of chronic opiate addicts. "	( Methadone maintenance treatment: dispelling myths and recovering truths. Neshin, SF, 1993)	3.17
"Most methadone treatment programs have insufficient resources to provide medical care."	( Providing medical care to methadone clinic patients: referral vs on-site care. Bigelow, GE; Ginn, DH; Pabst, KM; Umbricht-Schneiter, A, 1994)	1.04
"Methadone treatment and medical cover within the GMS Scheme emerged as important influences on the behaviour of clients with respect to general practitioners."	( The use of primary care services by drug users attending a HIV prevention unit. Bury, G; O'Kelly, F; Pomeroy, L, 1993)	1.01
"Methadone maintenance treatment for patients with opiate addiction, started in the Canton of Basel in 1980, today includes more than 600 patients, with a marked increase since 1987 due to a change in inclusion criteria following the spreading of HIV infections. "	( [Substitute drug treatments with methadone]. Ladewig, D; Petitjean, S; Stohler, R; von Bardeleben, U, 1993)	2.01
"A methadone treatment research clinic."	( Dose-response effects of methadone in the treatment of opioid dependence. Bigelow, GE; Liebson, IA; Stitzer, ML; Strain, EC, 1993)	1.31
"Methadone treatments have become the most efficient means of treating addicts who are not able or willing to start short term abstinence programmes or go to specialized institutions."	( [Clinical aspects and evaluation of methadone substitution therapy]. Déglon, JJ, )	1.13
"Methadone treatment for opioid dependence needs to be promoted and liberalized, especially because the oral route of administration eliminates the risks accompanying drug injection."	( Inadequate treatment of opioid dependence due to society's attitudes and beliefs. Blansfield, HN, 1996)	1.02
"Methadone treatment can reduce illicit drug use, needle sharing, and the social costs and health risks of heroin addiction. "	( Opiate-dependent patients receiving methadone. How physicians should manage therapy. Kahan, M; Sutton, N, 1996)	2.01
"(Methadone maintenance treatment for drug users leads to a more regulated life and makes it possible to implement measures to ameliorate their living conditions.) Fewer Surinam and Netherlands Antillean drug users are referred to general practice than native Dutch drug users."	( [More of the Surinam and Antilles drug addicts involved in the GG&GD (Community Medical and Health Service) methadone program in Amsterdam should be referred to the family physician for their methadone maintenance]. de Vries, HJ; Kanhai, K; van Brussel, GH, 1997)	1.13
"Methadone substitution treatment, which has been proven effective in reducing the negative effects associated with opiate use, has been used in Canada, but so far only on a small scale."	( The case for a heroin substitution treatment trial in Canada. Fischer, B; Rehm, J, )	0.85
"Methadone maintenance treatment programme newly established in Geneva, Switzerland."	( Predictors of patient retention in a newly established methadone maintenance treatment programme. del Rio, M; Mino, A; Perneger, TV, 1997)	1.99
"With methadone treatment, there is a decline in the amount of heroin used and in the number of injections."	( [Substitution therapy of drug addicts]. Kopferschmitt, J; Weber, JC, 1998)	0.76
"Methadone maintenance treatment (MMT) involves the daily administration of the oral opioid agonist methadone as a treatment for opioid dependence-a persistent disorder with a substantial risk of premature death. "	( Role of maintenance treatment in opioid dependence. Hall, W; Mattick, RP; Ward, J, 1999)	1.75
"Methadone treatment is most frequently used."	( [Problems with maintenance therapy in opiate dependence and the clinical importance of methadone]. Wilczek, H, 1998)	1.24
"Methadone treatment does not reduce opioid dependency but compensates for neurobiological complications of long-term use."	( [Methadone used in the treatment of opioid dependence]. Blix, O; Krook, A; Olsen, H; Waal, H, 1999)	1.93
"Methadone hydrochloride treatment is the most common pharmacological intervention for opioid dependence, and recent interest has focused on expanding methadone treatment availability beyond traditional specially licensed clinics. "	( Moderate- vs high-dose methadone in the treatment of opioid dependence: a randomized trial. Bigelow, GE; Liebson, IA; Stitzer, ML; Strain, EC, 1999)	2.06
"Methadone treatment during pregnancy offers overwhelming advantages compared with the less acceptable option of medical detoxification or the unacceptably dangerous option of leaving heroin-addicted women dependent on street drugs. "	( The methadone-maintained pregnancy. Doberczak, TM; Jantunen, M; Kandall, SR; Stein, J, 1999)	2.3
"Methadone maintenance treatment (MMT) for opioid addiction is safe and effective but underutilized because of inaccessibility, under-financing and the stigma generally attached to maintenance therapies. "	( Access to narcotic addiction treatment and medical care: prospects for the expansion of methadone maintenance treatment. Lewis, DC, 1999)	1.97
"Methadone treatment suggests a novel therapeutic approach for patients presenting 'variant' SCLC and non-SCLC morphologies, since they respond less to conventional therapy."	( Effects of bombesin on methadone-induced apoptosis of human lung cancer cells. Heusch, WL; Maneckjee, R, 1999)	1.34
"Methadone is used as a treatment for opiate detoxification in methadone maintenance programs. "	( The roles of P-glycoprotein and intracellular metabolism in the intestinal absorption of methadone: in vitro studies using the rat everted intestinal sac. Barthe, L; Bouër, R; Houin, G; Philibert, C; Tournaire, C; Woodley, J, 1999)	1.97
"Methadone treatment is most effective for pregnant women who receive care in a comprehensive service center. "	( Methadone treatment during pregnancy. Wang, EC, )	3.02
"Methadone maintenance treatment for heroin (diamorphine) addiction has been extensively researched. "	( A risk-benefit analysis of methadone maintenance treatment. Bell, J; Zador, D, 2000)	2.05
"Methadone treatment in Canada features a long, turbulent, and instructive history as an exemplary case study in public policy."	( Prescriptions, power and politics: the turbulent history of methadone maintenance in Canada. Fischer, B, 2000)	1.27
"Methadone treatment reduced the measured areas under the time-concentration curve (AUC0-6) by 63% for ddI (p =.04) and by 25% for d4T (p =.005) and the extrapolated AUCs for the full dosing interval (AUC0-12) by 57% for ddI (p =.11) and by 23% for d4T (p =."	( Interaction of methadone with didanosine and stavudine. Andrews, L; Charles, C; Friedland, G; Jatlow, P; McCance-Katz, EF; Mitchell, SM; Rainey, PM, 2000)	1.38
"Methadone treatment for heroin addiction has followed three distinct periods in Geneva, Switzerland. "	( [Forensic medicine experiences with methadone substitution in the Geneva canton]. Deglon, JJ; La Harpe, R; Perret, G, )	1.85
"Some methadone maintenance treatment (MMT) programs prescribe inadequate daily methadone doses. "	( When "enough" is not enough: new perspectives on optimal methadone maintenance dose. Eap, CB; Leavitt, SB; Maxwell, S; Paris, P; Shinderman, M, )	0.89
"Methadone treatment had a beneficial effect on HIV risk behaviors, and though some risk behaviors improved signiticantly for both groups, comorbid subjects continued to have higher rates of HIV risk factors than noncomorbid subjects."	( Influence of psychiatric comorbidity on HIV risk behaviors: changes during drug abuse treatment. Brooner, RK; Kidorf, MS; King, VL; Stoller, KB, 2000)	1.03
"Methadone reduction treatment processes were associated with poor outcomes, and many patients who were allocated to methadone reduction treatment did not receive reduction treatment as intended."	( Outcomes after methadone maintenance and methadone reduction treatments: two-year follow-up results from the National Treatment Outcome Research Study. Gossop, M; Marsden, J; Stewart, D; Treacy, S, 2001)	1.38
"Methadone treatment had no effect on craving or mood."	( Effects of methadone on cognition, mood and craving in detoxifying opiate addicts: a dose-response study. Bearn, J; Curran, HV; Kleckham, J; Strang, J; Wanigaratne, S, 2001)	1.42
"Methadone maintenance treatment has been an important part of the response to opiate misuse in Dublin since 1992."	( Opiate-related deaths in Dublin. Barry, J; Ward, M, )	0.85
"Methadone treatment programme for 50 opiate addicts has been conducted at the Department of Clinical Toxicology for a one year. "	( [Evaluation of health status in participants from a methadone treatment program in Krakow after one year of maintenance treatment]. Foryś, Z; Kamenczak, A; Maj, JC; Pach, J, 2001)	2
"Methadone maintenance treatment has been shown in many studies to reduce mortality and morbidity among heroin users. "	( Methadone maintenance treatment can be provided in a primary care setting without increasing methadone-related mortality: the Sheffield experience 1997-2000. Keen, J; Mathers, N; Oliver, P, 2002)	3.2
"Methadone treatment is often criticized by drug war supporters not because of its limitations, but because its very effectiveness highlights the meagre benefits of supply reduction."	( Methadone and heroin prescription: babies and bath water. Wodak, A, 2002)	2.48
"Methadone treatment was planned for no longer than 10 days while psychiatric supportive services were made available to continue as needed."	( Outpatient vs hospital methadone detoxification: an experimental comparison. Elms, RR; Thomson, CP; Wilson, BK, 1975)	1.29
"The methadone treatment was found to increase the rate of preimplantation deaths consistently in all post-meiotic stages with all doses used."	( On the mutagenicity of methadone hydrochloride. Induced dominant lethal mutation and spermatocyte chromosomal aberrations in treated males. Badr, FM; Badr, RS; Rabouh, SA, 1979)	1.05
"Oral methadone treatment, previously shown to increase selectively epoxide hydrase activity in male Wistar rats, also failed to alter the amount of BP bound to hepatic macromolecules."	( The irreversible binding of benzo[a]pyrene to rat liver macromolecules in vivo and in vitro: effects of agents that influence benzo[a]pyrene metabolism. Bellward, GD; Gontovnick, LS; Ng, S, 1979)	0.71
"The methadone-maintenance treatment program at this time is the most satisfactory approach to the treatment of heroin addiction."	( Drug addiction in pregnancy and the neonate. Ackerman, BD; Blinick, G; Jerez, E; Wallach, RC, 1976)	0.74
"No methadone-treated patient required modification of the therapeutic regimen, whereas eight of eleven placebo-treated patients needed treatment with methadone."	( Assessment and management of opioid withdrawal symptoms in buprenorphine-dependent subjects. Camí, J; Fernández, T; Ollé, JM; Peri, JM; San, L; Torrens, M, 1992)	0.8
"Methadone treatment reduced maternal weight gain but had no effect on either the frequency of resorptions or birthweight."	( Prenatal administration of methadone using the osmotic minipump: effects on maternal and offspring toxicity, growth, and behavior in the rat. Brake, SC; Church, S; Hutchings, DE; Malowany, D; Nero, TJ; Zmitrovich, A, )	1.15
"Methadone pretreatments may provide a convenient mechanism for the production and examination of long-term mu-opiate receptor physical dependence."	( Time course of naloxone-precipitated withdrawal after acute methadone exposure in humans. Bigelow, GE; Felch, LJ; June, HL; Stitzer, ML; Wright, C, 1991)	1.24
"Methadone treatment offers a first step toward social rehabilitation for drug addicts who have been living as criminals on the fringe of society."	( [Nicotine--drug addiction--AIDS. Drug use habits of Vienna addicts]. Hollerer, E; Loimer, N; Pfersmann, V; Presslich, O; Schmid-Siegel, B; Vedovelli, H; Werner, E, 1991)	1
"Methadone treatment offers a first step toward social rehabilitation for drug addicts who have been living as criminals on the fringe of society."	( [Stabilizing the social and health status of drug dependent patients with methadone. Long-term maintainance therapy--Vienna results]. Hollerer, E; Loimer, N; Pfersmann, V; Presslich, O; Schmid-Siegel, B; Werner, E, 1991)	1.23
"Methadone treatment and the use of needle exchanges were related in subsequent analysis to the sharing of injecting equipment."	( The sharing of injecting equipment among drug users attending prescribing clinics and those using needle-exchanges. Faugier, J; Hayes, C; Klee, H; Morris, J, 1991)	1
"Methadone treatment is one of the most helpful means of reducing the risk of acquired immunodeficiency syndrome available, provided that programs of quality are expanded."	( Methadone treatment and acquired immunodeficiency syndrome. Cooper, JR, )	2.3
"Methadone treatment per se was not documented to produce increasing rates of alcohol consumption or to cause large numbers of alcohol related problems in prospective studies."	( Alcohol and opioids: possible interactions of clinical importance. Cushman, P, 1987)	0.99
"Methadone treatment alone was not associated with increased abnormal movements."	( Prevalence of movement disorder in a methadone-maintained population. Gaspari, J; Kleber, H; Riordan, C; Santangelo, S; Swift, R, 1985)	1.26
"Methadone, as used in treatment schedules for narcotic dependence produces no significant effect on measures of human skills performance."	( The influence of analgesic drugs in road crashes. Chesher, GB, 1985)	0.99
"Methadone-treated subjects show a similar effect at phagocytic level but far less evident."	( Morphine and methadone impact on human phagocytic physiology. Avico, U; Borelli, G; Cavallo, G; Croce, C; Pacifici, R; Santiangeli, C; Tubaro, E; Zuccaro, P, 1985)	1.36
"Methadone treatment offers the opportunity to constructively intervene in the lives of these patients by helping to prevent the further spread of AIDS and by providing medical, psychiatric, and social services."	( Treatment of intravenous drug users with AIDS: the role of methadone maintenance. Batki, SL, )	1.1
"Methadone maintenance treatment involves a great deal of governmental regulations and controls which have to be enforced by the clinician, thus having important transferential implications for therapy. "	( Issues of transference in methadone maintenance treatment. Curet, ER; Langrod, J; Lowinson, JH; Page, J, 1985)	2.01
"Treatment with methadone and buprenorphine has the additional risk of diversion and misuse of medication."	( Medication Treatment of Opioid Use Disorder. Bell, J; Strang, J, 2020)	0.9
"Treatment with methadone or buprenorphine is the current standard of care for opioid use disorder. "	( Association of Racial/Ethnic Segregation With Treatment Capacity for Opioid Use Disorder in Counties in the United States. Cerdá, M; Goedel, WC; Hadland, SE; Marshall, BDL; Shapiro, A; Tsai, JW, 2020)	0.91
"Treatment with methadone is associated with severe cardiac arrhythmias, a side effect that seems to result from an inhibition of cardiac hERG K⁺ channels. "	( The opioid methadone induces a local anaesthetic-like inhibition of the cardiac Na⁺ channel, Na(v)1.5. Ahrens, J; de la Roche, J; Eberhardt, E; Foadi, N; Lampert, A; Leffler, A; O'Reilly, AO; Schulze, V; Stoetzer, C; Wegner, F, 2014)	1.15
"Treatment with methadone significantly increased H1N1 viral replication in lungs."	( Methadone enhances human influenza A virus replication. Chen, ML; Chen, YH; Chien, WH; Tsai, MT; Wang, Y; Wu, KL, 2017)	2.24
"Treatment with methadone was found to be both less expensive and more effective than treatment with buprenorphine, which suggests methadone dominates buprenorphine."	( Buprenorphine versus methadone maintenance: a cost-effectiveness analysis. Ali, R; Bell, J; Doran, CM; Mattick, RP; Shanahan, M; White, J, 2003)	0.98
"Treatment with methadone, for both pain and opioid dependence, should be preceded by an abuse liability evaluation."	( Methadone- and heroin-related deaths in Florida. Gold, MS; Goldberger, BA; Graham, NA; Merlo, LJ, 2008)	2.13
"Treatment with methadone or naltrexone did not result in a transaminase increase in these patients."	( [Effect of methadone or naltrexone on the course of transaminases in parenteral drug users with hepatitis C virus infection]. Gutiérrez Mora, E; Lozano Polo, JL; Martínez Pérez, V; Santamaría Gutiérrez, J; Vada Sánchez, J; Vallejo Correas, JA, 1997)	1.03
"Treatment with methadone is the standard of care for the opiate-using pregnant woman, despite findings challenging its benefits and efficacy in women who continue to use illicit drugs."	( Methadone treatment during pregnancy. Wang, EC, )	1.93
"The treatment with methadone was unstable and only 11% had received stable prolonged maintenance treatment."	( The influence of prolonged stable methadone maintenance treatment on mortality and employment: an 8-year follow-up. Bay, H; Mygind, O; Segest, E, 1990)	0.88
"Pretreatment with methadone and atropine resulted in the complete closure of the sphincter of Oddi for three hours, and the complete retention of bile in the gall bladder."	( Post prandial and cholecystokinin-induced emptying of the gall bladder in dogs. de Vries-Chalmers Hoynck van Papendrecht, R; Rothuizen, J; van den Brom, WE, 1990)	0.6

Toxicity

Study outcomes will determine what dose of baclofen is safe to prescribe to those receiving methadone.

Excerpt	Reference	Relevance
"A sudden and potentially lethal toxic reaction to a previously well-tolerated maintenance dose of methadone occurred in 4 of 6 monkeys."	( Sudden toxicity of methadone in monkeys: behavioral and electrophysiological evidence. Beck, EC; Dustman, RE; Snyder, EW; Straight, RC; Wayne, AW, 1977)	0.8
"Previous studies have shown that acute administration of methadone to male rats prior to mating results in adverse effects on their progeny, particularly decreased birth weights and increased neonatal mortality."	( Chronic methadone administration to male rats: tolerance to adverse effects on sires and their progeny. Joffe, JM; Peterson, JM; Smith, SM; Soyka, LF, 1978)	0.94
"A double-blind study of patients selected at random compared the analgesic and adverse effects of intrathecal methadone (1 mg) with those of intrathecal morphine (0."	( Intrathecal methadone and morphine for postoperative analgesia: a comparison of the efficacy, duration, and side effects. Brody, MC; Chabal, C; Ireton, RC; Jacobson, L; Ward, RJ, 1989)	0.87
" Lofexidine significantly reduced opiate withdrawal symptoms without the adverse sedative and hypotensive effects that limit the safety and usefulness of clonidine."	( Opiate withdrawal using lofexidine, a clonidine analogue with fewer side effects. Geyer, G; Resnick, RB; Washton, AM, 1983)	0.27
" No apparent alteration in the food efficiency index was detected, thus maternal malnutrition may not have been a factor in producing adverse effects on offspring."	( Developmental toxic effect after subcutaneous injections of methadone in Charles River CD-1 mice. Bui, QQ; Sperling, F; West, WL, 1983)	0.51
" As a basis for designing a questionnaire aimed at the IDU population, we conducted 5 focus groups to collect information on knowledge of and attitudes toward safe sex as held by male and female IDUs in methadone treatment."	( Safe sex? Misconceptions, gender differences and barriers among injection drug users: a focus group approach. Quirinale, J; Weiss, SH; Weston, CB, 1993)	0.47
"To assess the effect of opioid substitution (substituting one member of the opioid class for another) on the incidence and severity of adverse effects in palliative care patients who experience unacceptable, refractory adverse effects when taking an opioid drug."	( Opioid substitution to reduce adverse effects in cancer pain management. Ashby, MA; Jackson, KA; Martin, P, 1999)	0.3
" 49 substitutions were for adverse effects."	( Opioid substitution to reduce adverse effects in cancer pain management. Ashby, MA; Jackson, KA; Martin, P, 1999)	0.3
"We found that the incidence and severity of adverse effects differed between opioids in the same patient."	( Opioid substitution to reduce adverse effects in cancer pain management. Ashby, MA; Jackson, KA; Martin, P, 1999)	0.3
"Rapid opiate detoxification under general anaesthesia is a safe and efficient method to suppress withdrawal symptoms."	( Safety, efficacy, and long-term results of a modified version of rapid opiate detoxification under general anaesthesia: a prospective study in methadone, heroin, codeine and morphine addicts. Hensel, M; Kox, WJ, 2000)	0.51
" Various strategies have been proposed to estimate safe and effective starting doses of methadone when rotating from morphine and hydromorphone; however, there are no guidelines for estimating safe and effective starting doses of methadone when rotating from fentanyl."	( Intravenous methadone in the management of chronic cancer pain: safe and effective starting doses when substituting methadone for fentanyl. Fischberg, DJ; Khojainova, N; Kornick, C; Manfredi, P; Payne, R; Primavera, LH; Santiago-Palma, J, 2001)	0.91
"1 mg/hour of methadone may be safe and effective."	( Intravenous methadone in the management of chronic cancer pain: safe and effective starting doses when substituting methadone for fentanyl. Fischberg, DJ; Khojainova, N; Kornick, C; Manfredi, P; Payne, R; Primavera, LH; Santiago-Palma, J, 2001)	1.06
" Participants in the DM group reported many more adverse events than did subjects on placebo (173 vs."	( A randomized, double-blind, placebo-controlled safety study of high-dose dextromethorphan in methadone-maintained male inpatients. Bead, V; Caruso, FS; Childress, AR; Cornish, JW; Ehrman, RN; Esmonde, CA; Herman, BH; Martz, K; O'Brien, CP; Poole, S; Robbins, SJ, 2002)	0.53
"The study estimated serious adverse event (SAE) rates among entrants to pharmacotherapies for opioid dependence, during treatment and after leaving treatment."	( Serious adverse events in the Australian National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD). Digiusto, E; Mattick, RP; O'Brien, S; Ritter, A; Shakeshaft, A, 2004)	0.32
" No adverse effect on crime, hospital admissions, or death could be attributed to the legislative change in treatment organization."	( Adverse events due to change in organization of problem drug users' treatment? Buhl, L; Saelan, H; Sørensen, TM, 2004)	0.32
"We evaluated a novel intervention designed to improve access to sterile syringes and safe syringe disposal for injection drug users (IDUs) newly enrolled in methadone maintenance, through interviews with two sequential cohorts of 100 recent entrants into a methadone program in the Bronx, NY."	( Improving access to sterile syringes and safe syringe disposal for injection drug users in methadone maintenance treatment. Arnsten, JH; Gourevitch, MN; McNeely, J, 2006)	0.75
" The information was collectively considered and, using the best available evidence, translated into safe dosing guidelines for methadone induction."	( Methadone induction doses: are our current practices safe? Kahan, M; Srivastava, A, 2006)	1.98
" Recommendations are made for safe methadone induction doses."	( Methadone induction doses: are our current practices safe? Kahan, M; Srivastava, A, 2006)	2.05
" It addressed: safe storage of methadone takeaways; knowledge of risk of methadone ingestion by small children; and information provision from health care providers about the safe storage of methadone."	( Safe storage of methadone takeaway doses - a survey of patient practice. Lea, T; Winstock, AR, 2007)	0.97
" Eighty-seven per cent had discussed safe storage of takeaways with a health professional."	( Safe storage of methadone takeaway doses - a survey of patient practice. Lea, T; Winstock, AR, 2007)	0.69
"Clinicians should ensure patients are adequately informed about safe takeaway storage and the risk of methadone ingestion by children."	( Safe storage of methadone takeaway doses - a survey of patient practice. Lea, T; Winstock, AR, 2007)	0.9
" This study examined occurrences of serious adverse events (SAEs) reported in multicenter psychosocial trials of the National Institute on Drug Abuse Clinical Trials Network."	( Serious adverse events in randomized psychosocial treatment studies: safety or arbitrary edicts? Ball, SA; Blaine, J; Carroll, KM; Kirby, KC; McCarty, D; Peirce, JM; Petry, NM; Roll, JM; Rounsaville, BJ; Stitzer, M, 2008)	0.35
" Many analgesics, including opioids, have adverse effects on older adults with multiple co-morbidities."	( Methadone: an effective, safe drug of first choice for pain management in frail older adults. Gallagher, R, 2009)	1.8
" The pharmacology of methadone in frail elders is reviewed to demonstrate the specific benefits of the drug in older adults and how adverse events can be minimized."	( Methadone: an effective, safe drug of first choice for pain management in frail older adults. Gallagher, R, 2009)	2.11
"To investigate spontaneous reports of TdP present in the public version of the FDA Adverse Event Reporting System (AERS) in the light of what is already known on their TdP-liability."	( Drug-induced torsades de pointes: data mining of the public version of the FDA Adverse Event Reporting System (AERS). De Ponti, F; Moretti, U; Poluzzi, E; Raschi, E, 2009)	0.35
" Cases were represented by TdP reports, whereas non-cases were all reports of adverse drug reactions other than TdP."	( Drug-induced torsades de pointes: data mining of the public version of the FDA Adverse Event Reporting System (AERS). De Ponti, F; Moretti, U; Poluzzi, E; Raschi, E, 2009)	0.35
"Large spontaneous reporting databases represent an important source for signal detection of rare adverse drug reactions (ADR), such as TdP."	( Drug-induced torsades de pointes: data mining of the public version of the FDA Adverse Event Reporting System (AERS). De Ponti, F; Moretti, U; Poluzzi, E; Raschi, E, 2009)	0.35
" There were few adverse events or side effects and no deaths occurred during treatment."	( Feasability and safety of transfer from racemic methadone to (R)-methadone in primary care: clinical results from an open study. Soyka, M; Zingg, C, 2009)	0.61
" Antiviral treatment with pegylated interferon-alfa (IFN-alpha) plus ribavirin is often complicated by psychiatric adverse events, significantly affecting patients adherence."	( Hepatitis C treatment in patients with drug addiction: clinical management of interferon-alpha-associated psychiatric side effects. Mauss, S; Schaefer, M, 2008)	0.35
" Coincident with the rise in the prescribing of these drugs has been a substantial increase in pediatric opioid toxicities and adverse events."	( Methadone and buprenorphine toxicity in children. Boyer, EW; Marcus, S; McCance-Katz, EF, )	1.57
" The objective of this study involving 130 methadone-maintained outpatients receiving VBRT was to investigate whether resets (a) increase risk for adverse events (AEs) and (b) delay return to abstinence in relation to magnitude of voucher reset."	( Resets do not appear to increase the rate of adverse events or prolong relapse in voucher-based reinforcement therapy. Bresani, E; Carpenedo, CM; Dugosh, KL; Kirby, KC; Rosenwasser, BJ; Versek, BE, 2010)	0.62
" Our results indicate that varenicline is safe to give to this subject population, as there were no adverse events related to medication during this study."	( The safety and efficacy of varenicline in cocaine using smokers maintained on methadone: a pilot study. Gonsai, K; Poling, J; Rounsaville, B; Severino, K; Sofuoglu, M, )	0.36
" Withdrawal also creates an adverse environment for the developing fetal brain that can have long-term health effects."	( Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers: can we assure the safety of the fetus? McCarthy, JJ, 2012)	0.61
" With respect to the particular consumed drug substances other than opioids during pregnancy variable forms of teratogenic and toxic effects can be assigned to the baby."	( [Pregnant opioid addicted patients and additional drug intake. Part I. Toxic effects and therapeutic consequences]. Havemann-Reinecke, U; Hoell, I, 2011)	0.37
" No serious adverse events could be detected during opioid rotation."	( Practicability, safety, and efficacy of a "German model" for opioid conversion to oral levo-methadone. Gaertner, J; Klein, C; Nauck, F; Ostgathe, C; Sabatowski, R; Van Aaaken, A; Voltz, R, 2012)	0.6
"The presented study indicates that the GMLC provides a practical and reasonably safe approach to perform opioid rotation to levo-methadone in a palliative care setting."	( Practicability, safety, and efficacy of a "German model" for opioid conversion to oral levo-methadone. Gaertner, J; Klein, C; Nauck, F; Ostgathe, C; Sabatowski, R; Van Aaaken, A; Voltz, R, 2012)	0.8
" We assessed prevalence, adverse events, and effectiveness of varenicline treatment in this cohort."	( Low incidence of adverse events following varenicline initiation among opioid dependent smokers with comorbid psychiatric illness. Arnsten, JH; Bernstein, SL; Nahvi, S; Richter, KP; Wu, B, 2013)	0.39
" Of 82 varenicline courses, nine (11%) were discontinued due to adverse events and two due to depressive symptoms."	( Low incidence of adverse events following varenicline initiation among opioid dependent smokers with comorbid psychiatric illness. Arnsten, JH; Bernstein, SL; Nahvi, S; Richter, KP; Wu, B, 2013)	0.39
"Despite substantial comorbidity, opioid-dependent smokers receiving integrated substance abuse, medical and psychiatric care had few documented adverse events with varenicline treatment."	( Low incidence of adverse events following varenicline initiation among opioid dependent smokers with comorbid psychiatric illness. Arnsten, JH; Bernstein, SL; Nahvi, S; Richter, KP; Wu, B, 2013)	0.39
"How best to measure the occurrence of adverse events during a randomized clinical trial is an issue that has not been adequately examined in the research literature."	( Nonserious adverse events in randomized trials with opioid-dependent pregnant women: direct versus indirect measurement. Arria, AM; Coyle, MG; Heil, SH; Jones, HE; Kaltenbach, K; Martin, PR; O'Grady, KE; Selby, P; Stine, SM, 2012)	0.38
"A secondary analysis of nonserious adverse events that occurred in the Maternal Opioid Treatment: Human Experimental Research (MOTHER) Study was undertaken."	( Nonserious adverse events in randomized trials with opioid-dependent pregnant women: direct versus indirect measurement. Arria, AM; Coyle, MG; Heil, SH; Jones, HE; Kaltenbach, K; Martin, PR; O'Grady, KE; Selby, P; Stine, SM, 2012)	0.38
"The two methods of recording adverse events failed to agree on where differences in the frequency of occurrence of adverse events between the medication conditions might exist."	( Nonserious adverse events in randomized trials with opioid-dependent pregnant women: direct versus indirect measurement. Arria, AM; Coyle, MG; Heil, SH; Jones, HE; Kaltenbach, K; Martin, PR; O'Grady, KE; Selby, P; Stine, SM, 2012)	0.38
"Findings suggest indirect examination of occurrence of adverse events should be cautiously undertaken, because indirect assessment of adverse events makes no distinction between what might be simply typical variation in behavior rather than systematic changes in behavior attributable to study condition, and lacks coverage of the full spectrum of adverse events."	( Nonserious adverse events in randomized trials with opioid-dependent pregnant women: direct versus indirect measurement. Arria, AM; Coyle, MG; Heil, SH; Jones, HE; Kaltenbach, K; Martin, PR; O'Grady, KE; Selby, P; Stine, SM, 2012)	0.38
"Contemporaneous direct measurement of adverse events likely yield reasonably valid estimates of the rate of occurrence of the adverse events, while indirect measu-rement of adverse events may not be sufficiently reliable."	( Nonserious adverse events in randomized trials with opioid-dependent pregnant women: direct versus indirect measurement. Arria, AM; Coyle, MG; Heil, SH; Jones, HE; Kaltenbach, K; Martin, PR; O'Grady, KE; Selby, P; Stine, SM, 2012)	0.38
"In order to reduce the rate of poisoning, we recommend the use of child-resistant containers for dispensing syrup, reduction in methadone concentration, adding a coloring agent, special flavor, and education of patients on the safe storage of methadone in their home in order to reduce the occurrence of accidental poisonings."	( Methadone toxicity: comparing tablet and syrup formulations during a decade in an academic poison center of Iran. Hassanian-Moghaddam, H; Noroozi, A; Rahimi, M; Shadnia, S; Soltaninejad, K, )	1.78
" These results in a large study sample from Taiwan suggest that the gene dose of CYP2C19 may potentially serve as an indicator for the plasma R-methadone/methadone dose ratio and cardiac side effect in patients receiving methadone maintenance therapy."	( Functional genetic polymorphisms in CYP2C19 gene in relation to cardiac side effects and treatment dose in a methadone maintenance cohort. Chang, YS; Chen, AC; Chen, CH; Ho, IK; Hsiao, CF; Huang, CL; Kuo, HW; Lin, KM; Lin, L; Liu, ML; Liu, SC; Liu, SW; Liu, YL; Su, LW; Tan, HK; Tsou, HH; Wang, SC; Wu, CS; Wu, HY; Yang, YH, 2013)	0.8
"IV-PCA provided timely, safe and useful analgesia for patients with severe breakthrough pain and may be useful to help titration of opioids, weaning to oral analgesia and to decide for interventional procedures."	( Safety profile of intravenous patient-controlled analgesia for breakthrough pain in cancer patients: a case series study. Ashmawi, HA; Cascudo, GM; de Santana Neto, J; Guimaraes, GM; Neto, JO; Sousa, AM, 2014)	0.4
" Seventy-two percent of all patients discontinued their long-acting opioid regimens before 90 days due to adverse effects or insufficient pain relief."	( Patterns of care and side effects for patients prescribed methadone for treatment of chronic pain. Dobscha, SK; Grimaldi, EM; Macey, TA; Morasco, BJ; Weimer, MB, )	0.38
" Safe use of methadone requires clinical skills and knowledge in use of methadone to mitigate potential risks, including serious risks related to risk of overdose and cardiac arrhythmias."	( Methadone safety: a clinical practice guideline from the American Pain Society and College on Problems of Drug Dependence, in collaboration with the Heart Rhythm Society. Chou, R; Compton, P; Cruciani, RA; Farrar, JT; Fiellin, DA; Haigney, MC; Inturrisi, C; Knight, JR; Marcus, SM; Mehta, D; Meyer, MC; Otis-Green, S; Portenoy, R; Savage, S; Strain, E; Walsh, S; Zeltzer, L, 2014)	2.21
"Seven-day point prevalence abstinence verified by expired carbon monoxide (CO) < 8 parts per million at week 12 (primary outcome); carbon monoxide (CO)-verified abstinence, cigarettes/day, incident Axis I psychiatric illness, suicidal ideation or serious adverse events (SAEs) at weeks 2, 4, 8, 12 or 24 (secondary outcomes)."	( Varenicline efficacy and safety among methadone maintained smokers: a randomized placebo-controlled trial. Arnsten, JH; Nahvi, S; Ning, Y; Richter, KP; Segal, KS, 2014)	0.67
"Opioid substitution treatment (OST) for opioid dependence may be limited by adverse events (AEs)."	( Safety and tolerability of slow-release oral morphine versus methadone in the treatment of opioid dependence. Babic-Hohnjec, L; Berthel, T; Bonorden-Kleij, K; Gholami, N; Haasen, C; Hämmig, R; Höpner, D; Köhler, W; Lebentrau, K; Reimer, J; Ruckes, C; Verthein, U; Vollmert, C; Weber, B, 2014)	0.64
" The most frequent treatment-emergent non-OWS adverse events were headache, nausea, constipation, and neck pain."	( Switching Opioid-Dependent Patients From Methadone to Morphine: Safety, Tolerability, and Methadone Pharmacokinetics. Cape, G; Devane, J; Friedhoff, L; Glue, P; Gray, A; Harland, S; Howes, J; Hung, CT; Hung, N; Lam, F; Lockhart, M; Tunnicliff, D; Weis, H, 2016)	0.7
" Two reviewers assessed independently the titles and abstracts of all search results and full texts of potentially eligible studies reporting original data for maternal/fetal/infant death, preterm birth, fetal growth outcomes, fetal/congenital anomalies, fetal/child neurodevelopment and/or maternal adverse events."	( Buprenorphine compared with methadone to treat pregnant women with opioid use disorder: a systematic review and meta-analysis of safety in the mother, fetus and child. Amick, HR; Jones, HE; Joyce, AR; Kim, MM; Mann, AL; Murrelle, EL; Zedler, BK, 2016)	0.73
"In outpatients with advanced cancer, rotation to methadone as a second-line opioid was efficacious and safe when using a tiered scheme with close follow-up by experienced health professionals."	( Efficacy and Safety of Methadone as a Second-Line Opioid for Cancer Pain in an Outpatient Clinic: A Prospective Open-Label Study. Garzón-Rodríguez, C; González-Barboteo, J; Llorens-Torromé, S; Porta-Sales, J; Villavicencio-Chávez, C, 2016)	1
" Although more research into methadone rotation strategies is still needed, this study describes a successful tiered scheme of oral methadone rotation that was proven safe and effective during follow-up."	( Efficacy and Safety of Methadone as a Second-Line Opioid for Cancer Pain in an Outpatient Clinic: A Prospective Open-Label Study. Garzón-Rodríguez, C; González-Barboteo, J; Llorens-Torromé, S; Porta-Sales, J; Villavicencio-Chávez, C, 2016)	1.04
" The aims of the present study were to examine the acute toxic effects of methadone, an opioid receptor agonist and NMDA receptor antagonist, as well as to evaluate the protective properties of recombinant human GH (rhGH) on methadone-induced toxicity."	( Growth hormone is protective against acute methadone-induced toxicity by modulating the NMDA receptor complex. Diwakarla, S; Grönbladh, A; Hallberg, M; Nyberg, F; Nylander, E; Zelleroth, S, 2016)	0.93
"To study drug safety and the reporting behavior of adverse drug reactions (ADR) related to agents used for opioid replacement therapy (ORT) we conducted a cross-sectional questionnaire-based telephone survey among physicians who provide outpatient ORT in Germany (n=176; response rate=55."	( Drug safety and adverse drug reaction reporting behavior related to outpatient opioid replacement therapy: Results from a survey among physicians. Cabanis, M; Connemann, BJ; Eller, J; Freudenmann, RW; Gahr, M; Hiemke, C; Lang, D; Schönfeldt-Lecuona, C, 2017)	0.46
" Consistent safe injection, however, was inversely associated with age (aOR=0."	( Correlates of willingness to initiate pre-exposure prophylaxis and anticipation of practicing safer drug- and sex-related behaviors among high-risk drug users on methadone treatment. Altice, FL; Copenhaver, M; Huedo-Medina, TB; Karki, P; Madden, L; Meyer, JP; Shrestha, R, 2017)	0.65
" It has a number of qualities that make its use favorable, including lack of known active metabolites and presumed relative safety from adverse effects such as opioid-induced neurotoxicity (OIN)."	( Methadone-Induced Neurotoxicity in Advanced Cancer: A Case Report. Hartwig, KN; Hoff, AM; Rosielle, DA, 2017)	1.9
" In Norway, there has been vocal patient resistance to the newest medication, buprenorphine-naloxone (BNX), and complaints have focused on the side effect profile."	( Dissatisfaction with opioid maintenance treatment partly explains reported side effects of medications. Bjørnestad, R; Clausen, T; Muller, AE, 2018)	0.48
" Among each medication group, dissatisfaction with medications or OMT in general along with poor health status increased the relative risk ratio of reporting the heaviest side effect burden."	( Dissatisfaction with opioid maintenance treatment partly explains reported side effects of medications. Bjørnestad, R; Clausen, T; Muller, AE, 2018)	0.48
"To investigate the incidence of perioperative adverse events in patients receiving intravenous methadone for major spine surgery."	( Safety profile of intraoperative methadone for analgesia after major spine surgery: An observational study of 1,478 patients. Alpert, SB; Dunn, LK; Durieux, ME; Fang, S; Hanak, MF; Leibowitz, MK; Naik, BI; Nemergut, EC; Tsang, S; Yerra, S, )	0.63
" With no difference in medical and safety outcomes and a significant reduction in charges, the MAiN model can be considered safe and cost-effective."	( Early Treatment Innovation for Opioid-Dependent Newborns: A Retrospective Comparison of Outcomes, Utilization, Quality, and Safety, 2006-2014. Charron, E; Chen, L; Dickes, L; Hudson, JA; Mayo, R; Sherrill, WW; Summey, J, 2018)	0.48
" There is a need to better understand risk for adverse outcomes during and after OAT, and for innovative approaches to identifying people at greatest risk of adverse outcomes."	( Using routinely collected data to understand and predict adverse outcomes in opioid agonist treatment: Protocol for the Opioid Agonist Treatment Safety (OATS) Study. Ali, R; Degenhardt, L; Dobbins, T; Fiellin, DA; Hickman, M; Jones, NR; Larney, S; Mattick, RP; Nielsen, S, 2018)	0.48
" We will use standard regression techniques to model the magnitude and risk factors for adverse outcomes (eg, mortality, unplanned hospitalisation and emergency department presentation, and unplanned treatment cessation) during and after OAT, and machine learning approaches to develop a risk-prediction model."	( Using routinely collected data to understand and predict adverse outcomes in opioid agonist treatment: Protocol for the Opioid Agonist Treatment Safety (OATS) Study. Ali, R; Degenhardt, L; Dobbins, T; Fiellin, DA; Hickman, M; Jones, NR; Larney, S; Mattick, RP; Nielsen, S, 2018)	0.48
" This review provides information on the pharmacology and the toxic effects of pharmacologic agents that are used to treat opioid use disorder."	( Pharmacologic Treatment of Opioid Use Disorder: a Review of Pharmacotherapy, Adjuncts, and Toxicity. Boyer, EW; Burns, MM; Chai, PR; Toce, MS, 2018)	0.48
" The goal was to develop guidelines for safe and effective management of methadone therapy in hospice and palliative care."	( Safe and Appropriate Use of Methadone in Hospice and Palliative Care: Expert Consensus White Paper. Bemben, NM; Bruera, E; Chou, R; Davis, MP; Lapointe, BJ; Lockman, DK; Malotte, K; McPherson, ML; Paice, J; Ray, JB; Reddy, A; Salpeter, S; Walker, KA; Wellman, C, 2019)	1.04
" Single doses up to 150 mg and daily doses up to 75 mg for 10 days were well tolerated with mostly mild treatment-emergent adverse events and no severe or serious adverse events."	( Characterization of the Safety and Pharmacokinetic Profile of D-Methadone, a Novel N-Methyl-D-Aspartate Receptor Antagonist in Healthy, Opioid-Naive Subjects: Results of Two Phase 1 Studies. Bernstein, G; Davis, K; Inturrisi, C; Manfredi, PL; McDonnell, M; Mills, C; Oldenhof, J; Vitolo, OV; Wang, L, )	0.37
" However, although opioids have been appropriately used in Japan, they rarely induce serious adverse events, such as respiratory depression."	( Current Status of Adverse Events Related with Opioid Analgesics in Japan: Assessment Based on Japanese Adverse Drug Event Report Database. Futamura, A; Nakagawa, T; Suga, Y; Sugawara, H; Suzuki, S; Takase, H; Torigoe, K; Uchida, M; Uesawa, Y, 2019)	0.51
"Best practice guidelines for the safe and compassionate care of critically ill children necessitates the use of sedation to ensure adequate ventilation, patient safety and comfort."	( Effect of a Sedation Weaning Protocol on Safety and Medication Use among Hospitalized Children Post Critical Illness. Curley, MAQ; Greco, CD; Morrill, DR; O'Donnell, KA; Solodiuk, JC, )	0.13
" Reported adverse effects of methadone include constipation, respiratory depression, dizziness, nausea, vomiting, itching, sweating, rhabdomyolysis, QT prolongation, and orthostatic hypotension."	( Methadone associated long term hearing loss and nephrotoxicity; a case report and literature review. Brent, J; Ghasemi, S; Izadpanahi, S; Mehrpour, O; Yaghoubi, MA, 2019)	2.25
" There were no differences in clinical outcomes or adverse events."	( Intraoperative Methadone Is Associated with Decreased Perioperative Opioid Use Without Adverse Events: A Case-Matched Cohort Study. Caruso, TJ; Kleiman, ZI; Kwiatkowski, DM; Robinson, JD; Wu, M, 2020)	0.91
"Intraoperative methadone use was associated with a decrease in perioperative opioid exposure in patients undergoing congenital heart surgery and was not associated with adverse events or prolonged durations of mechanical ventilation or ICU stay."	( Intraoperative Methadone Is Associated with Decreased Perioperative Opioid Use Without Adverse Events: A Case-Matched Cohort Study. Caruso, TJ; Kleiman, ZI; Kwiatkowski, DM; Robinson, JD; Wu, M, 2020)	1.26
" Appropriate patient selection to ensure safe and effective treatment by a team of clinicians who appreciate and are familiar with methadone and its unique pharmacology is crucial."	( Emerging Challenges to the Safe and Effective Use of Methadone for Cancer-Related Pain in Paediatric and Adult Patient Populations. Ajayi, TA; Atayee, RS; Edmonds, KP; Saunders, IM; Willeford, A, 2020)	1.01
" The MMR provides a guide to safe and effective dosing, an alternative to the pharmacokinetically 'blind' dosing algorithms currently in use."	( The Use of the Methadone/Metabolite Ratio (MMR) to Identify an Individual Metabolic Phenotype and Assess Risks of Poor Response and Adverse Effects: Towards Scientific Methadone Dosing. Fassbender, C; Graas, J; Leamon, MH; McCarthy, JJ; Vasti, EJ; Ward, C, )	0.48
"Development of novel testing strategies to detect adverse human health effects is of interest to replace in vivo-based drug and chemical safety testing."	( Integrating in vitro data and physiologically based kinetic modeling-facilitated reverse dosimetry to predict human cardiotoxicity of methadone. Bouwmeester, H; Rietjens, IMCM; Shi, M; Strikwold, M, 2020)	0.76
"This study suggests MMT is safe despite repeated exposure to fentanyl while taking methadone."	( One year of methadone maintenance treatment in a fentanyl endemic area: Safety, repeated exposure, retention, and remission. Carroll, JJ; Green, TC; Rich, JD; Stone, AC, 2020)	1.16
" Guidelines on the safe use of methadone have limited applicability to children since their cardiac intervals differ from those of adults."	( Methadone's Effect on Cardiac Repolarization: Safety in the PICU. Friedman, SD; Kovach, JR; Thompson, NE, 2020)	2.29
" The use of a single large dose of intraoperative methadone is controversial due to inconsistent reductions in total opioid use in children and adverse effects."	( A Novel Perioperative Multidose Methadone-Based Multimodal Analgesic Strategy in Children Achieved Safe and Low Analgesic Blood Methadone Levels Enabling Opioid-Sparing Sustained Analgesia With Minimal Adverse Effects. Aruldhas, BW; Fitzgerald, RE; Overholser, BR; Packiasabapathy, S; Quinney, SK; Renschler, JS; Sadhasivam, S; Zang, Y; Zhang, P, 2021)	1.16
"Novel multiple small perioperative methadone doses resulted in safe and lower blood methadone levels, <100 ng/mL, a threshold previously associated with respiratory depression."	( A Novel Perioperative Multidose Methadone-Based Multimodal Analgesic Strategy in Children Achieved Safe and Low Analgesic Blood Methadone Levels Enabling Opioid-Sparing Sustained Analgesia With Minimal Adverse Effects. Aruldhas, BW; Fitzgerald, RE; Overholser, BR; Packiasabapathy, S; Quinney, SK; Renschler, JS; Sadhasivam, S; Zang, Y; Zhang, P, 2021)	1.18
" This preliminary retrospective cross-sectional audit of safety improvement intiative underscores the importance of providing treatment services to those with opioid use disorders and that methadone is safe among this population with a high burden of comorbidity, most of which leads to negative outcomes from COVID-19."	( Is Methadone Safe for Patients With Opioid Use Disorder and Coronavirus Disease 2019 Infection? Benson, M; Carvalho, D; Maplanka, M; Oluseye, L; Owiti, JA, )	0.94
"To assess the pharmacokinetics, clinical efficacy, and adverse effects of injectable methadone with the pharmacokinetic enhancer fluconazole (methadone-fluconazole), compared with the standard formulation of injectable methadone, in dogs after ovariohysterectomy."	( Long-acting injectable methadone (methadone-fluconazole) provides safe and effective postoperative analgesia in a randomized clinical trial for dogs undergoing soft tissue surgery. Berke, KA; Bieberly, ZD; Comroe, AJ; Fitzgerald, AH; Jugan, MC; Klocke, EE; Klutzke, JB; KuKanich, B; KuKanich, KS; Mason, DE; Orchard, RJ; Upchurch, DA; Woodruff, K, 2022)	1.26
"Study outcomes will determine what dose of baclofen is safe to prescribe to those receiving methadone, to inform a subsequent proof-of-concept trial of the efficacy baclofen to facilitate opiate detoxification."	( FORWARDS-1: an adaptive, single-blind, placebo-controlled ascending dose study of acute baclofen on safety parameters in opioid dependence during methadone-maintenance treatment-a pharmacokinetic-pharmacodynamic study. Barker, D; Cro, S; Lingford-Hughes, AR; Mozgunov, P; Nahar, L; Paterson, LM; Paterson, S; Phillips, R; Smith, C, 2022)	1.14
" Our objective was to assess the safety of rapid inpatient methadone initiation with regard to mortality, overdose, and serious adverse outcomes both in-hospital and postdischarge."	( Safety of rapid inpatient methadone initiation protocol: A retrospective cohort study. Berger, O; Bou Harfouch, LT; Buresh, ME; Patel, SM; Racha, S, 2023)	1.45
" The study had no major adverse events including in-hospital or thirty-day post-discharge overdoses or deaths."	( Safety of rapid inpatient methadone initiation protocol: A retrospective cohort study. Berger, O; Bou Harfouch, LT; Buresh, ME; Patel, SM; Racha, S, 2023)	1.21
" We examined associations between highest BUP-NX and methadone doses, and (1) percentage of opioid-positive urine drug screens (UDS); (2) retention in the assigned treatment; and (3) adverse events (AEs)."	( Associations of methadone and buprenorphine-naloxone doses with unregulated opioid use, treatment retention, and adverse events in prescription-type opioid use disorders: Exploratory analyses of the OPTIMA study. Ahamad, K; Bakouni, H; Foll, BL; Jutras-Aswad, D; Lim, R; McAnulty, C; Socias, ME; Tatar, O, 2023)	1.51
"Pharmacotherapeutic options for the treatment of opioid withdrawal are limited by abuse potential, adverse effects, and lack of availability of existing drugs."	( Efficacy and safety of tramadol in the treatment of opioid withdrawal: A meta-analysis of randomized controlled trials. Maiti, R; Mishra, BR; Mohapatra, D; Padhan, M, 2023)	0.91
" The primary outcome was adverse events associated with methadone, specifically opioid toxicity or sedation requiring increased medical observation or intervention."	( Safety and Efficacy of Rapid Methadone Titration for Opioid Use Disorder in an Inpatient Setting: A Retrospective Cohort Study. Bach, P; Fairbairn, N; Klaire, S; McLean, M; Nolan, S; Ryan, A, )	0.67
"In this inpatient cohort, rapid methadone titration was well tolerated and resulted in patients reaching higher doses of methadone than would be possible with a standard schedule, with few adverse events."	( Safety and Efficacy of Rapid Methadone Titration for Opioid Use Disorder in an Inpatient Setting: A Retrospective Cohort Study. Bach, P; Fairbairn, N; Klaire, S; McLean, M; Nolan, S; Ryan, A, )	0.71

Pharmacokinetics

The long half-life and wide inter-patient variability in clearance of methadone make this drug difficult to use optimally. Methadone in plasma concentrations and its metabolite EDDP in microsomes were determined by ultra-high-performance liquid chromatography.

Excerpt	Reference	Relevance
" Serum and urine ZDV and ZDV-glucuronide concentrations were measured by both high pressure liquid chromatography (HPLC) and radioimmunoassay (RIA), and pharmacokinetic parameters determined at least twice in each of nine methadone-maintained former IVDU patients initiating ZDV therapy."	( Pharmacokinetic interactions of zidovudine and methadone in intravenous drug-using patients with HIV infection. Brechbühl, AB; Friedland, GH; Kahl, P; Miller, MA; Schwartz, EL; Selwyn, PA, 1992)	0.73
"To determine the relationship between changes in plasma methadone concentration and pharmacodynamic effects, plasma methadone profiles and pharmacodynamics (analgesia and sedation) were measured during and after the continuous infusion of methadone for 180 to 270 minutes in 15 patients with pain caused by cancer."	( Pharmacokinetic-pharmacodynamic relationships of methadone infusions in patients with cancer pain. Colburn, WA; Foley, KM; Inturrisi, CE; Max, MB; Portenoy, RK, 1990)	0.78
" Methadone plasma concentration-time data were fit to a one-compartment pharmacokinetic model by extended least-squares regression."	( Altered methadone pharmacokinetics in pregnancy: implications for dosing. Camara, P; DePetrillo, P; Dudley, M; Griffiths, W; Swift, RM, 1989)	1.62
" It has the following pharmacokinetic properties: high lipophilicity, large volume of distribution (initial and steady state), low clearance (hepatic capacity limited) with a long terminal elimination time, high bioavailability following oral administration, and a tendency to accumulate in the blood and tissues."	( [Methadone--pharmacokinetics and pharmacodynamics of an opiate]. Jage, J, 1989)	1.19
"The long half-life and wide inter-patient variability in clearance of methadone make this drug difficult to use optimally."	( Estimation of methadone clearance: application in the management of cancer pain. Cherry, DA; Cousins, MJ; Gourlay, GK; Plummer, JL, 1988)	0.87
" Recent pharmacokinetic studies have confirmed the rationale for regular administration of oral morphine and methadone but have revealed marked interindividual differences in the kinetics and metabolism which must be considered when titrating the oral dose according to the individual patient's need."	( High-dose morphine and methadone in cancer patients. Clinical pharmacokinetic considerations of oral treatment. Säwe, J, )	0.65
" The long half-life of methadone was associated with prolonged pain relief."	( A comparative study of the efficacy and pharmacokinetics of oral methadone and morphine in the treatment of severe pain in patients with cancer. Cherry, DA; Cousins, MJ; Gourlay, GK, 1986)	0.82
" The intravenous administration of 2 resulted in two sequential half-lives of 3 and 270 min and no apparent pharmacokinetic dose dependency."	( Pharmacokinetics of morphine and its surrogates. VII: High-performance liquid chromatographic analyses and pharmacokinetics of methadone and its derived metabolites in dogs. Derendorf, H; Garrett, ER; Mattha, AG, 1985)	0.48
" The multi compartment polyexponential pharmacokinetic models have classically been fit to data using nonlinear regression programs such as NonLin (Metzler, 1969)."	( New method that gives true least squares fit of one and two compartment open pharmacokinetic models applied to valproic acid and methadone. Gerber, N; Lawyer, CH, 1980)	0.47
" In five subjects treated with ammonium chloride (acidic urine), the plasma half-life of methadone was found to be 19."	( Clinical pharmacokinetics of methadone. Anggård, E; Meresaar, U; Nilsson, MI, 1982)	0.78
" Pharmacokinetic parameters were calculated for the intravenous dose assuming a two compartment of open model."	( Single dose pharmacokinetics and bioavailability of methadone in man studied with a stable isotope method. Anggård, E; Holmstrand, J; Meresaar, U; Nilsson, MI, 1981)	0.51
" There was no significant difference between the pharmacokinetic parameters of (R)-methadone and (S)-methadone following administration of the individual enantiomers."	( Stereoselective pharmacokinetics of methadone in beagle dogs. Brune, K; Geisslinger, G; Schmidt, N; Williams, KM, 1994)	0.79
" The disposition of methadone at steady-state was assessed on 8 occasions-in 5 opioid addicts prescribed wide ranging doses of methadone (10 mg to 60 mg per day)-providing unique pharmacokinetic data."	( Steady-state pharmacokinetics of methadone in opioid addicts. Calvert, R; Hay, AW; Raistrick, D; Wolff, K, 1993)	0.89
" The pharmacokinetic parameters of the R- and S-enantiomers of the racemate are reported."	( Stereoselective pharmacokinetics of methadone in chronic pain patients. Angelo, HR; Blemmer, T; Christrup, LL; Drenck, NE; Kristensen, K; Rasmussen, SN; Sjøgren, P, 1996)	0.57
" The median elimination half-life of methadone in healthy subjects was 33-46 h depending on the method used to calculate this parameter."	( The pharmacokinetics of methadone in healthy subjects and opiate users. Calvert, R; Feely, M; Hay, AW; Raistrick, D; Rostami-Hodjegan, A; Shires, S; Tucker, GT; Wolff, K, 1997)	0.88
"Estimates of the long terminal elimination half-life of methadone (33-46 h in healthy subjects and, possibly, longer in opiate users) indicated that accurate measurement of this parameter requires a duration of sampling longer than that used in this study."	( The pharmacokinetics of methadone in healthy subjects and opiate users. Calvert, R; Feely, M; Hay, AW; Raistrick, D; Rostami-Hodjegan, A; Shires, S; Tucker, GT; Wolff, K, 1997)	0.85
" Pharmacokinetic data sets for dextromoramide in each subject were conducted and analysed further, indicating short elimination half-life values (71 min, range 31-152 min)."	( Determination and pharmacokinetics of dextromoramide in methadone maintenance therapy. de Vos, JW; Ufkes, JG; van Brussel, GH, 1998)	0.55
" Factors such as inter- and intraindividual pharmacokinetic variability and changes in AZT intracellular concentrations should be considered as other mechanisms responsible for changes in AZT pharmacokinetics with concomitant therapies."	( Glucuronidation of 3'-azido-3'-deoxythymidine (zidovudine) by human liver microsomes: relevance to clinical pharmacokinetic interactions with atovaquone, fluconazole, methadone, and valproic acid. Collins, JM; Jamis-Dow, C; Klecker, RW; Trapnell, CB, 1998)	0.5
"A randomized, double-blinded, placebo-controlled pharmacokinetic and safety trial was conducted to determine the effect of fluconazole on methadone disposition."	( The effect of fluconazole on the clinical pharmacokinetics of methadone. Brown, LS; Cobb, MN; Desai, J; Rainey, PM; Zannikos, PN, 1998)	0.74
" The estimates of pharmacokinetic parameters based on unbound plasma concentrations did not differ between groups, with the sole exception of the unbound apparent volume of distribution."	( Altered plasma and brain disposition and pharmacodynamics of methadone in abstinent rats. Calvo, R; Garrido, MJ; Trocóniz, IF; Valle, M, 1999)	0.54
" Therefore, we have developed a population-based pharmacokinetic (POP-PK) model that characterises adaptive changes in methadone kinetics."	( Population pharmacokinetics of methadone in opiate users: characterization of time-dependent changes. Calvert, R; Hay, AW; Raistrick, D; Rostami-Hodjegan, A; Tucker, GT; Wolff, K, 1999)	0.8
"To determine plasma racemic methadone concentration-effect relationships for subjective and objective responses and whether pharmacokinetic and/or pharmacodynamic factors influence withdrawal severity."	( Steady-state pharmacokinetics and pharmacodynamics in methadone maintenance patients: comparison of those who do and do not experience withdrawal and concentration-effect relationships. Bochner, F; Dyer, KR; Foster, DJ; Menelaou, A; Somogyi, AA; White, JM, 1999)	0.85
" Subjective symptoms and pharmacodynamic measures were assessed throughout the study period."	( Three oral formulations of methadone. A clinical and pharmacodynamic comparison. Freeman, K; Gourevitch, MN; Hartel, D; Hecht, J; Lowinson, J; Marion, I; Tenore, P, 1999)	0.6
" The assay was applied to plasma protein and erythrocyte binding studies and a 96-h pharmacokinetic study in two healthy female volunteers following oral dosing with rac-methadone."	( Development and application of a chiral high performance liquid chromatography assay for pharmacokinetic studies of methadone. Boulton, DW; Devane, CL, 2000)	0.71
"Eighteen patients recruited from a public methadone maintenance program underwent an interdosing interval pharmacokinetic study."	( Steady-state pharmacokinetics of (R)- and (S)-methadone in methadone maintenance patients. Bochner, F; Dyer, KR; Foster, DJ; Somogyi, AA; White, JM, 2000)	0.83
" Considerable interindividual variability was observed for the pharmacokinetic parameters, with coefficients of variation of up to 70%."	( Steady-state pharmacokinetics of (R)- and (S)-methadone in methadone maintenance patients. Bochner, F; Dyer, KR; Foster, DJ; Somogyi, AA; White, JM, 2000)	0.57
" Our data has provided the basis for a population-based pharmacokinetic (POP-PK) model which is intended for use as a clinical tool in association with plasma measurements in methadone maintenance patients."	( Population-based pharmacokinetic approach for methadone monitoring of opiate addicts: potential clinical utility. Hay, AW; Raistrick, D; Rostami-Hodjegan, A; Tucker, G; Wolff, K, 2000)	0.76
"A 24-hour methadone pharmacokinetic study was performed before antiretroviral therapy was begun and after 15 days of therapy."	( Effect of ritonavir/saquinavir on stereoselective pharmacokinetics of methadone: results of AIDS Clinical Trials Group (ACTG) 401. Aberg, J; Aweeka, F; D'Amico, R; Flexner, C; Gal, J; Gerber, JG; Gulick, R; Hsu, A; Hughes, V; Mildvan, D; Rosenkranz, S; Segal, Y, 2001)	0.95
" Pharmacokinetic and pharmacodynamic modeling was used to assess the influence of the above-mentioned covariables on methadone enantiomer disposition and actions."	( Pharmacokinetics and pharmacodynamics of methadone enantiomers after a single oral dose of racemate. Arnaud, P; Boulton, DW; DeVane, CL, 2001)	0.79
"The pharmacokinetic profile of the active enantiomer of methadone, R -methadone, showed a relatively normal distribution with 38% to 90% of the interindividual variability in modeled pharmacokinetic parameters being explained by their individual variability in CYP3A activity, the cumulative amount of the main CYP3A4 metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrolidine, excreted in the urine, the fraction unbound in plasma, and the alpha1-AGP orosomucoid 2 (ORM2) variant plasma concentration."	( Pharmacokinetics and pharmacodynamics of methadone enantiomers after a single oral dose of racemate. Arnaud, P; Boulton, DW; DeVane, CL, 2001)	0.82
" 5,510 +/- 237 microg/L), or terminal elimination half-life (t 1/2; 55."	( The pharmacokinetics of methadone following co-administration with a lamivudine/zidovudine combination tablet in opiate-dependent subjects. Andrews, L; Friedland, GH; Jatlow, P; Lane, B; McCance-Katz, EF; Mitchell, SM; Rainey, PM; Snidow, JW, 2002)	0.62
" For the iv groups (CO(iv) and OP(iv)), the Cp-analgesic effect relationship was described by an E(max) sigmoid model and omeprazole did not affect the pharmacodynamic parameters."	( Effect of omeprazole on oral and intravenous RS-methadone pharmacokinetics and pharmacodynamics in the rat. Calvo, R; Carlos, MA; Carlos, R; Du Souich, P; Lukas, JC; Suarez, E, 2002)	0.57
" Each sex corresponded to a distinct subpopulation of the PK parameters and one of the pharmacodynamic parameters (Emax)."	( Sex specificity in methadone analgesia in the rat: a population pharmacokinetic and pharmacodynamic approach. Calvo, R; Carlos, MA; Lukas, JC; Ortega, I; Rodriguez, M; Suarez, E, 2002)	0.64
" A comparison is also presented between several methods based on animal pharmacokinetic data, using the same set of proprietary compounds, and it lends further support for the use of this method, as opposed to methods that require the gathering of pharmacokinetic data in laboratory animals."	( Prediction of human volume of distribution values for neutral and basic drugs. 2. Extended data set and leave-class-out statistics. Gao, F; Lombardo, F; Obach, RS; Shalaeva, MY, 2004)	0.32
" Pharmacokinetic evaluations of total and unbound methadone enantiomers (R and S) were conducted before and after SQV/rtv."	( The effects of once-daily saquinavir/minidose ritonavir on the pharmacokinetics of methadone. Berenson, CS; Buggé, CJ; Cloen, D; de Caprariis, PJ; DiFrancesco, R; Esch, A; Espinosa, O; Hewitt, RG; Ljungqvist, A; Palic, B; Schur, JL; Shelton, MJ, 2004)	0.8
"To construct a population pharmacokinetic model for methadone enantiomers in the setting of methadone maintenance treatment for opioid dependence."	( Population pharmacokinetics of (R)-, (S)- and rac-methadone in methadone maintenance patients. Bochner, F; Foster, DJ; Somogyi, AA; White, JM, 2004)	0.83
"A population pharmacokinetic model was developed using P-Pharm software for rac-, (R)- and (S)-methadone using data (8-13 plasma samples per subject) obtained from 59 methadone maintenance patients during one interdosing interval at steady state."	( Population pharmacokinetics of (R)-, (S)- and rac-methadone in methadone maintenance patients. Bochner, F; Foster, DJ; Somogyi, AA; White, JM, 2004)	0.8
"Phase I, open-label, fixed-sequence, pharmacokinetic drug-drug interaction study."	( Effect of tenofovir disoproxil fumarate on the pharmacokinetics and pharmacodynamics of total, R-, and S-methadone. Berenson, CS; Booker, BM; Bullock, JM; Cloen, D; Coakley, DF; Flaherty, JF; Haas, CE; Kearney, BP; Liaw, S; Smith, PF; Yale, K, 2004)	0.54
" Both AUCss and Cmax met the strict criteria for bioequivalence between the two study periods for total, R-, and S-methadone, indicating a lack of drug interaction when tenofovir DF was coadministered with methadone."	( Effect of tenofovir disoproxil fumarate on the pharmacokinetics and pharmacodynamics of total, R-, and S-methadone. Berenson, CS; Booker, BM; Bullock, JM; Cloen, D; Coakley, DF; Flaherty, JF; Haas, CE; Kearney, BP; Liaw, S; Smith, PF; Yale, K, 2004)	0.75
"Prospective, open-label, within-subject pharmacokinetic study."	( Pharmacokinetics and pharmacodynamics of methadone enantiomers after coadministration with amprenavir in opioid-dependent subjects. Bigelow, GE; Christopher, J; Fuchs, EJ; Hendrix, CW; Lou, Y; Martinez, E; Snidow, JW; Wakeford, J; Wire, MB, 2004)	0.59
"Standard pharmacokinetic parameters were determined from the concentrations and compared between the two treatments (methadone alone vs methadone with amprenavir)."	( Pharmacokinetics and pharmacodynamics of methadone enantiomers after coadministration with amprenavir in opioid-dependent subjects. Bigelow, GE; Christopher, J; Fuchs, EJ; Hendrix, CW; Lou, Y; Martinez, E; Snidow, JW; Wakeford, J; Wire, MB, 2004)	0.8
" During maintenance treatment with methadone, treatment with other drugs may be necessary due to the frequent comorbidity of drug addicts: psychotropic drugs, antibiotics, anticonvulsants and antiretroviral drugs, which can cause pharmacokinetic interactions."	( Methadone--metabolism, pharmacokinetics and interactions. Bertolini, A; Coccia, CP; Ferrari, A; Sternieri, E, 2004)	2.04
"Methadone is effective for chronic cancer pain, but its early pharmacodynamic profile and effectiveness for breakthrough pain remain uncertain."	( Characterization of the early pharmacodynamic profile of oral methadone for cancer-related breakthrough pain: a pilot study. Fisher, K; Hagen, NA; Stiles, C, 2004)	2.01
"The stimulant effect of caffeine, as an additive in diacetylmorphine preparations for study purposes, may interfere with the pharmacodynamic effects of diacetylmorphine."	( Population pharmacokinetics of caffeine and its metabolites theobromine, paraxanthine and theophylline after inhalation in combination with diacetylmorphine. Beijnen, JH; de Jonge, ME; den Hoed, R; Hendriks, VM; Huitema, AD; Sparidans, RW; van den Brink, W; van Ree, JM; Zandvliet, AS, 2005)	0.33
"To determine if atazanavir, a once-daily protease inhibitor and moderate inhibitor of P450 CYP3A4, exhibited pharmacokinetic interactions with (R)-methadone."	( Lack of an effect of atazanavir on steady-state pharmacokinetics of methadone in patients chronically treated for opiate addiction. Agarwala, S; Andrews, L; Child, M; Daley, L; Friedland, G; O'Mara, E; Schreibman, T; Shi, J; Wang, Y, 2005)	0.76
"Methadone pharmacokinetic parameters were measured in 16 patients on chronic methadone therapy prior to and after 14 days of daily administration of atazanavir."	( Lack of an effect of atazanavir on steady-state pharmacokinetics of methadone in patients chronically treated for opiate addiction. Agarwala, S; Andrews, L; Child, M; Daley, L; Friedland, G; O'Mara, E; Schreibman, T; Shi, J; Wang, Y, 2005)	2.01
"No clinically relevant pharmacokinetic interactions were found between atazanavir and methadone."	( Lack of an effect of atazanavir on steady-state pharmacokinetics of methadone in patients chronically treated for opiate addiction. Agarwala, S; Andrews, L; Child, M; Daley, L; Friedland, G; O'Mara, E; Schreibman, T; Shi, J; Wang, Y, 2005)	0.79
" Blood samples and pharmacodynamic data were collected 10-12 times over a 24-h inter-dosing interval."	( Within- and between- subject variability in methadone pharmacokinetics and pharmacodynamics in methadone maintenance subjects. Bochner, F; Foster, DJ; Hanna, J; Salter, A; Somogyi, AA; White, JM, 2005)	0.59
" General dosing guidelines, dosage conversions from other opioids and pharmacokinetic issues in special populations are discussed."	( Pharmacokinetics of methadone. Kern, SE; Lugo, RA; Satterfield, KL, 2005)	0.65
" Recent studies with a 103-compound dataset suggested that scaling from monkey pharmacokinetic data tended to be the most accurate method for predicting human clearance."	( Extrapolation of preclinical pharmacokinetics and molecular feature analysis of "discovery-like" molecules to predict human pharmacokinetics. Evans, CA; Jolivette, LJ; Nagilla, R; Ward, KW, 2006)	0.33
" Global access to opioid agonist therapy and HIV treatment is expanding but when concurrently used, problematic pharmacokinetic drug interactions can occur."	( Pharmacokinetic drug interactions between opioid agonist therapy and antiretroviral medications: implications and management for clinical practice. Altice, FL; Bruce, RD; Friedland, GH; Gourevitch, MN, 2006)	0.33
"Clinical case series and carefully controlled pharmacokinetic interaction studies have been conducted between methadone and most approved antiretroviral therapies."	( Pharmacokinetic drug interactions between opioid agonist therapy and antiretroviral medications: implications and management for clinical practice. Altice, FL; Bruce, RD; Friedland, GH; Gourevitch, MN, 2006)	0.55
"Limited pharmacokinetic (PK) and pharmacodynamic (PD) data are available to use in methadone dosing recommendations in pediatric patients for either opioid abstinence or analgesia."	( Population-based analysis of methadone distribution and metabolism using an age-dependent physiologically based pharmacokinetic model. Beard, DA; Hines, RN; McCarver, DG; Tong, X; Yang, F, 2006)	0.85
" Mean population pharmacokinetic parameters for a 1-compartment model were 455 L and 338 L for apparent volume of distribution and 53."	( Pharmacokinetics and pharmacodynamics of methadone enantiomers in hospice patients with cancer pain. Auret, K; Boyd, F; Ilett, KF; Oh, TE; Page-Sharp, M; Roger Goucke, C, 2006)	0.6
" The objective of this study was to assess the clinical and pharmacokinetic interactions between methadone and nelfinavir."	( [Clinical and pharmacokinetic interactions between methadone and nelfinavir (Nemesia study)]. Cadafalch, J; Deig, E; Fuster, M; Marco, A; Pedrol, E; Valls, I, 2006)	0.8
"This trial was aimed to estimate the pharmacokinetic interaction between voriconazole and methadone at steady state in male patients on methadone therapy and to characterize the safety and tolerability profile during the coadministration."	( Pharmacokinetic interaction between voriconazole and methadone at steady state in patients on methadone therapy. Foster, G; Labadie, R; Liu, P; Sharma, A; Somoza, E, 2007)	0.81
" Knowledge of the pharmacokinetic and pharmacological properties of this compound remains particularly important for its appropriate prescription."	( [Methadone: from pharmacokinetic profile to clinical pharmacology]. Gury, C; Laqueille, X; Vazquez, V, )	1.04
"The aim of this study was to determine, using methadone pharmacokinetic properties, whether methadone dosage adjustments are needed on initiation of treatment with pegIFN alfa-2b for HCV in methadone-maintained HIV-positive patients."	( Effects of pegylated interferon alfa-2b on the pharmacokinetic and pharmacodynamic properties of methadone: a prospective, nonrandomized, crossover study in patients coinfected with hepatitis C and HIV receiving methadone maintenance treatment. Arnsten, JH; Berk, SI; Du, E; Gourevitch, MN; Litwin, AH; Soloway, I, 2007)	0.82
" No effect of valspodar on other pharmacokinetic parameters was discernible."	( Modeling methadone pharmacokinetics in rats in presence of P-glycoprotein inhibitor valspodar. Calvo, R; Ortega, I; Perez-Ruixo, JJ; Rodriguez, M; Suarez, E, 2007)	0.76
" Noncompartmental pharmacokinetic analysis was performed."	( Pharmacokinetics of methadone in human-immunodeficiency-virus-infected patients receiving nevirapine once daily. Arroyo, E; Climent-Grana, E; Merino, E; Pérez-Ruixo, JJ; Portilla, J; Valenzuela, B, 2007)	0.66
" High dose opioid administration (150% normal dose) was associated with reductions in overall SpO2 levels and performance (reaction time, DSST) in the methadone patients, but had virtually no impact on pharmacodynamic responses in the buprenorphine group."	( Pharmacodynamics of diazepam co-administered with methadone or buprenorphine under high dose conditions in opioid dependent patients. Bond, AJ; Lintzeris, N; Mitchell, TB; Nestor, L; Strang, J, 2007)	0.79
" Plasma concentrations and pharmacokinetic parameters of R- and S-methadone isomers were determined on days -1, 7, and 14 and of TMC125 on days 7 and 14."	( Pharmacokinetic and pharmacodynamic study of the concomitant administration of methadone and TMC125 in HIV-negative volunteers. De Smedt, G; Hoetelmans, RM; Kakuda, TN; Peeters, M; Schöller-Gyüre, M; Stevens, T; van den Brink, W; Vanaken, H; Vandermeulen, K; Woodfall, B, 2008)	0.81
" pharmacokinetic data on 670 drugs representing, to our knowledge, the largest publicly available set of human clinical pharmacokinetic data."	( Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds. Lombardo, F; Obach, RS; Waters, NJ, 2008)	0.35
" Seventeen methadone patients (7 depressed and 10 not depressed) had pharmacokinetic and pharmacodynamic assessments (opioid withdrawal, drug effects, and mood) over one 24-hour dosing interval."	( Major depressive disorder and patient satisfaction in relation to methadone pharmacokinetics and pharmacodynamics in stabilized methadone maintenance patients. Brands, B; Dunn, E; Elkader, AK; Selby, P; Sproule, BA, 2009)	0.98
" The PK profile of methadone was characterized by high clearance (Cl/F), small volume of distribution (V(d)/F) and short elimination half-life (t(1/2))."	( Pharmacokinetics of the injectable formulation of methadone hydrochloride administered orally in horses. Barker, SA; Hosgood, G; Linardi, RL; Natalini, CC; Short, C; Stokes, AM, 2009)	0.93
" The aim of this study is to analyze methadone dosage in responder and nonresponder patients considering pharmacogenetic and pharmacokinetic factors that may contribute to dosage adequacy."	( Contribution of cytochrome P450 and ABCB1 genetic variability on methadone pharmacokinetics, dose requirements, and response. Cuyàs, E; de la Torre, R; Díaz, L; Farré, M; Fonseca, F; Khymenets, O; Pastor, A; Pizarro, N; Torrens, M, 2011)	0.88
" A blood sample was collected from each horse before and at predetermined time points over a 360-minute period after each administration of the drug to determine serum drug concentration by use of gas chromatography-mass spectrometry analysis and to estimate pharmacokinetic parameters by use of a noncompartmental model."	( Bioavailability and pharmacokinetics of oral and injectable formulations of methadone after intravenous, oral, and intragastric administration in horses. Barker, SA; Hosgood, GL; Keowen, ML; Linardi, RL; Short, CR; Stokes, AM, 2012)	0.61
" Oral pharmacokinetics in horses included a short half-life (approx 1 hour), high total body clearance corrected for bioavailability (5 to 8 mL/min/kg), and small apparent volume of distribution corrected for bioavailability (0."	( Bioavailability and pharmacokinetics of oral and injectable formulations of methadone after intravenous, oral, and intragastric administration in horses. Barker, SA; Hosgood, GL; Keowen, ML; Linardi, RL; Short, CR; Stokes, AM, 2012)	0.61
" A randomized, single-dose, blinded, two-period, two-sequence, crossover pharmacokinetic study was performed in 24 healthy volunteers under fasting conditions."	( Pharmacokinetics of a new immediate-release methadone tablet formulation with decreased in vitro solubility. Vinson, RK, 2012)	0.64
" The pharmacokinetic parameters determined were: maximum plasma drug concentration (C(max)) of 38."	( Pharmacokinetics of a new immediate-release methadone tablet formulation with decreased in vitro solubility. Vinson, RK, 2012)	0.64
"This study provides the first complete set of pharmacokinetic data on a novel methadone formulation."	( Pharmacokinetics of a new immediate-release methadone tablet formulation with decreased in vitro solubility. Vinson, RK, 2012)	0.87
"The aims of the present study were to characterize the relationship between plasma racemic methadone and its enantiomers' concentrations with respect to their pharmacodynamic effects and to investigate the influence of potential covariates on the pharmacodynamic parameters in patients on methadone maintenance treatment (MMT)."	( Pharmacokinetic-pharmacodynamic modeling of mood and withdrawal symptoms in relation to plasma concentrations of methadone in patients undergoing methadone maintenance treatment. Iqbal, MZ; Lagundoye, O; Lennard, MS; Rostami-Hodjegan, A; Seivewright, N; Shiran, MR; Tucker, GT, 2012)	0.81
"The optimal methadone dosing regimen for children undergoing spinal surgery is uncertain because of sparse pediatric pharmacokinetic data and a paucity of analgesic effect data."	( The pharmacokinetics of methadone in adolescents undergoing posterior spinal fusion. Abel, MF; Anderson, BJ; Balireddy, R; Colquhoun, DA; Durieux, ME; Langman, LJ; Stemland, CJ; Thammishetti, S; Witte, J, 2013)	1.08
" The terminal elimination half-life was 44."	( The pharmacokinetics of methadone in adolescents undergoing posterior spinal fusion. Abel, MF; Anderson, BJ; Balireddy, R; Colquhoun, DA; Durieux, ME; Langman, LJ; Stemland, CJ; Thammishetti, S; Witte, J, 2013)	0.7
"Current pharmacokinetic parameter estimates in adolescents are similar to those reported in adults."	( The pharmacokinetics of methadone in adolescents undergoing posterior spinal fusion. Abel, MF; Anderson, BJ; Balireddy, R; Colquhoun, DA; Durieux, ME; Langman, LJ; Stemland, CJ; Thammishetti, S; Witte, J, 2013)	0.7
"The interindividual variability in the dose required for effective methadone maintenance treatment (MMT) for opioid addiction may be influenced in part by genetic variations in genes encoding pharmacodynamic factors of methadone."	( Association of genetic variation in pharmacodynamic factors with methadone dose required for effective treatment of opioid addiction. Adelson, M; Kreek, MJ; Levran, O; Ott, J; Peles, E; Randesi, M; Shen, PH; Shu, X, 2013)	0.86
" We outline the various pharmacokinetic mechanisms involved when combining TVR with methadone or morphine and recommend that current data are not sufficiently robust to minimize the potentially significant interaction with opioids, especially methadone."	( Potential P-glycoprotein pharmacokinetic interaction of telaprevir with morphine or methadone. Ashley, CC; Carlyn, C; Fontenelle, DV; Fudin, HR; Fudin, J; Hinden, DA, 2013)	0.84
"Open-label, two-period, single-sequence pharmacokinetic study."	( Effect of ritonavir-boosted danoprevir, a potent hepatitis C virus protease inhibitor, on the pharmacokinetics of methadone in healthy subjects undergoing methadone maintenance therapy. Bech, N; Brennan, BJ; Morcos, PN; Moreira, SA; Navarro, MT; Smith, PF, 2014)	0.61
" Pharmacokinetic parameters for the total concentrations of (R)- and (S)-methadone on Days -1 and 10 were determined using noncompartmental methods."	( Effect of ritonavir-boosted danoprevir, a potent hepatitis C virus protease inhibitor, on the pharmacokinetics of methadone in healthy subjects undergoing methadone maintenance therapy. Bech, N; Brennan, BJ; Morcos, PN; Moreira, SA; Navarro, MT; Smith, PF, 2014)	0.84
"Coadministration of DNVr with MMT resulted in no significant pharmacokinetic interactions or signs of methadone withdrawal."	( Effect of ritonavir-boosted danoprevir, a potent hepatitis C virus protease inhibitor, on the pharmacokinetics of methadone in healthy subjects undergoing methadone maintenance therapy. Bech, N; Brennan, BJ; Morcos, PN; Moreira, SA; Navarro, MT; Smith, PF, 2014)	0.83
" Pharmacodynamic (PD) measures and safety assessments were obtained throughout the study."	( Dolutegravir does not affect methadone pharmacokinetics in opioid-dependent, HIV-seronegative subjects. Bala, U; Chen, S; Geoffroy, P; Mark, S; Peppercorn, A; Piscitelli, S; Savina, P; Song, I; Wajima, T, 2013)	0.68
" Rilpivirine decreased methadone minimum and maximum plasma concentrations (Cmin ; Cmax ) and area under the plasma concentration-time curve versus methadone alone (least-square mean ratio; 90% confidence interval) by 22% (0."	( The effect of rilpivirine on the pharmacokinetics of methadone in HIV-negative volunteers. Buelens, A; Crauwels, HM; Hoetelmans, RM; Stevens, M; van Heeswijk, RP; Vandevoorde, A, 2014)	0.96
"The lack of methadone pharmacokinetic data in children and neonates restrains dosing to achieve the target concentration in these populations."	( The pharmacokinetics of methadone and its metabolites in neonates, infants, and children. Anderson, BJ; Drover, DR; Hammer, GB; Kern, S; Lugo, RA; Satterfield, K; Stemland, CJ; Tristani-Firouzi, M; Ward, RM, 2014)	1.09
"Current pharmacokinetic parameter estimates in children and neonates are similar to those reported in adults."	( The pharmacokinetics of methadone and its metabolites in neonates, infants, and children. Anderson, BJ; Drover, DR; Hammer, GB; Kern, S; Lugo, RA; Satterfield, K; Stemland, CJ; Tristani-Firouzi, M; Ward, RM, 2014)	0.71
"Following intramuscular injection, methadone was characterized by a large total volume of distribution, high systemic clearance and intermediate terminal half-life in sika deer."	( Population pharmacokinetics of methadone hydrochloride after a single intramuscular administration in adult Japanese sika deer (Cervus nippon nippon). Alvarez, JC; Limoges, MJ; Locatelli, Y; Marsot, A; Scala, C; Simon, N, 2015)	0.98
" Serial blood samples were taken for pharmacokinetic analysis."	( Effect of steady-state faldaprevir on the pharmacokinetics of steady-state methadone and buprenorphine-naloxone in subjects receiving stable addiction management therapy. Adeniji, A; Elgadi, M; Huang, F; Joseph, D; Riesenberg, RR; Schobelock, MJ; Vince, BD; Webster, LR, 2015)	0.65
" To identify potentially contributing covariates in methadone pharmacokinetics, we used population pharmacokinetic modeling to estimate clearance (CL/F) and volume of distribution (V/F) for each methadone enantiomer in an ethnically diverse methadone maintained population."	( Ethnic and genetic factors in methadone pharmacokinetics: a population pharmacokinetic study. Bart, G; Brundage, RC; Lenz, S; Straka, RJ, 2014)	0.94
" A linear one-compartment population pharmacokinetic model with first-order conditional estimation with interaction (FOCE-I) was used to evaluate methadone CL/F and V/F."	( Ethnic and genetic factors in methadone pharmacokinetics: a population pharmacokinetic study. Bart, G; Brundage, RC; Lenz, S; Straka, RJ, 2014)	0.89
" Population pharmacokinetics is a valuable method for identifying the influences on methadone pharmacokinetic variability."	( Ethnic and genetic factors in methadone pharmacokinetics: a population pharmacokinetic study. Bart, G; Brundage, RC; Lenz, S; Straka, RJ, 2014)	0.92
" The authors evaluated the pharmacokinetic interaction of boceprevir with methadone or buprenorphine/naloxone in patients on stable maintenance therapy."	( Pharmacokinetic interaction between HCV protease inhibitor boceprevir and methadone or buprenorphine in subjects on stable maintenance therapy. Bruce, RD; Butterton, JR; Feng, HP; Hulskotte, EG; Lin, WH; O'Mara, E; Wagner, JA; Webster, LR; Xuan, F, 2015)	0.88
" The AUC (6 hours ng mL(-1)) and CMAX (6 ng mL(-1)) of methadone significantly increased to 541 hours ng mL(-1) and 47."	( Chloramphenicol significantly affects the pharmacokinetics of oral methadone in Greyhound dogs. KuKanich, B; KuKanich, K, 2015)	0.9
"Effects of hemodialysis on pharmacokinetic properties and QTc were studied in 4 patients taking daily methadone dose of 100 mg (range, 60-120 mg)."	( Effects of Hemodialysis on Methadone Pharmacokinetics and QTc. Arnesen, M; Brørs, O; Gjesdal, K; Hullstein, I; Krajci, P; Kringen, M; Müller, LD; Opdal, MS; Sagedal, S; Sayed, K, 2015)	0.93
"The serum Cmin methadone level was 1124 nmol/L (range, 547-1581 nmol/L)."	( Effects of Hemodialysis on Methadone Pharmacokinetics and QTc. Arnesen, M; Brørs, O; Gjesdal, K; Hullstein, I; Krajci, P; Kringen, M; Müller, LD; Opdal, MS; Sagedal, S; Sayed, K, 2015)	1.07
"To characterize the population pharmacokinetics of oral methadone in neonates requiring pharmacologic treatment of neonatal abstinence syndrome and to develop a pharmacokinetic (PK) model toward an evidence-based treatment protocol."	( Pharmacokinetics of Oral Methadone in the Treatment of Neonatal Abstinence Syndrome: A Pilot Study. Akinbi, H; Isemann, B; Mizuno, T; Tabangin, ME; Vinks, AA; Ward, LP; Wiles, JR, 2015)	0.97
"To evaluate neonatal abstinence syndrome (NAS) treatment outcomes achieved using an optimized methadone weaning protocol developed using pharmacokinetic (PK) modeling compared with standard methadone weaning."	( Cohort Analysis of a Pharmacokinetic-Modeled Methadone Weaning Optimization for Neonatal Abstinence Syndrome. Hall, ES; Meinzen-Derr, J; Wexelblatt, SL, 2015)	0.9
" Pharmacokinetic evaluation showed that 91% of methadone was cleared during this time, with a mean elimination half-life of 59 hours."	( Switching Opioid-Dependent Patients From Methadone to Morphine: Safety, Tolerability, and Methadone Pharmacokinetics. Cape, G; Devane, J; Friedhoff, L; Glue, P; Gray, A; Harland, S; Howes, J; Hung, CT; Hung, N; Lam, F; Lockhart, M; Tunnicliff, D; Weis, H, 2016)	0.96
" It has been shown to exhibit large pharmacokinetic variability and concentration-QTc relationships."	( Population Genetic-Based Pharmacokinetic Modeling of Methadone and its Relationship with the QTc Interval in Opioid-Dependent Patients. Crettol, S; Csajka, C; Eap, CB; Guidi, M, 2016)	0.68
" However, this parameter is usually derived from a small database of human pharmacokinetic studies."	( Refining the excretion factors of methadone and codeine for wastewater analysis - Combining data from pharmacokinetic and wastewater studies. Bruno, R; Hall, W; Lai, FY; Mueller, JF; O'Brien, J; Prichard, J; Thai, PK; van Dyken, E, 2016)	0.71
" In children, the half-life of R- and S-methadone enantiomers was 34 ± 16 and 24 ± 9 hr, respectively."	( Pharmacokinetics and analgesic effects of methadone in children and adults with sickle cell disease. Deych, E; Frei-Jones, M; Horst, J; Kharasch, ED; Shannon, W, 2016)	0.97
" The relationship between plasma and saliva methadone enantiomer concentrations was investigated to determine if saliva could be a substitute for plasma in pharmacodynamic and pharmacokinetic studies for clinical monitoring and dose optimization of methadone in patients with advanced cancer."	( Can Saliva and Plasma Methadone Concentrations Be Used for Enantioselective Pharmacokinetic and Pharmacodynamic Studies in Patients With Advanced Cancer? George, R; Good, P; Hardy, J; Haywood, A; Hennig, S; Khan, S; Norris, R, 2017)	1.03
" Although the saliva-to-plasma ratio of the concentration of methadone enantiomers was stable across the dosing range, due to the variability in individual saliva-to-plasma ratios, saliva sampling may not be a valid substitute in pharmacokinetic studies of methadone in cancer."	( Can Saliva and Plasma Methadone Concentrations Be Used for Enantioselective Pharmacokinetic and Pharmacodynamic Studies in Patients With Advanced Cancer? George, R; Good, P; Hardy, J; Haywood, A; Hennig, S; Khan, S; Norris, R, 2017)	1.01
" This toxicity can be due in part to the pharmacogenetics of an individual, which influences the pharmacokinetic and pharmacodynamic properties of the drug."	( Effects of cytochrome P450 single nucleotide polymorphisms on methadone metabolism and pharmacodynamics. Ahmad, T; Rankin, GO; Valentovic, MA, 2018)	0.72
" To help develop appropriate pain management practices and to develop a quantitative model for predicting methadone dosimetry, a flow-limited multiroute physiologically based pharmacokinetic (PBPK) model for methadone in dogs constructed with Berkeley Madonna™ was developed."	( The construction and application of a population physiologically based pharmacokinetic model for methadone in Beagles and Greyhounds. Elwell-Cuddy, T; KuKanich, B; Li, M; Lin, Z, 2018)	0.91
" The data suggest that the assay is well suited for pharmacokinetic purposes."	( Enantioselective capillary electrophoresis for pharmacokinetic analysis of methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine in equines anesthetized with ketamine and isoflurane. Braun, C; Gittel, C; Larenza Menzies, MP; Sandbaumhüter, FA; Theurillat, R; Thormann, W, 2019)	0.74
"Our study aimed to evaluate the impacts of the cytochrome P450 (CYP) 2B6-G516T and CYP2D6 genetic polymorphisms on pharmacokinetic and clinical parameters in patients receiving methadone maintenance treatment."	( Relevance of CYP2B6 and CYP2D6 genotypes to methadone pharmacokinetics and response in the OPAL study. Bouquié, R; Challet-Bouju, G; Dano, C; Grall-Bronnec, M; Hardouin, JB; Laforgue, EJ; Le Geay, B; Leboucher, J; Verstuyft, C; Victorri-Vigneau, C, 2019)	0.97
"We conducted 2 phase 1, double-blind, randomized, placebo-controlled, single- and multiple-ascending-dose studies to investigate the safety and tolerability of oral D-methadone and to characterize its pharmacokinetic profile in healthy opioid-naive volunteers."	( Characterization of the Safety and Pharmacokinetic Profile of D-Methadone, a Novel N-Methyl-D-Aspartate Receptor Antagonist in Healthy, Opioid-Naive Subjects: Results of Two Phase 1 Studies. Bernstein, G; Davis, K; Inturrisi, C; Manfredi, PL; McDonnell, M; Mills, C; Oldenhof, J; Vitolo, OV; Wang, L, )	0.56
"Study 206216 (NCT02666001) was a Phase I, open-label study, assessing the effect of FTR 600 mg (extended-release formulation) twice daily on pharmacokinetics of MET or BUP and norBUP, in non-HIV-infected participants on stable maintenance therapy with MET (40-120 mg; n = 16) or BUP plus naloxone (8-24 mg plus 2-6 mg; n = 16); pharmacodynamic response was assessed using standard opioid rating scales."	( Methadone and buprenorphine pharmacokinetics and pharmacodynamics when coadministered with fostemsavir to opioid-dependent, human immunodeficiency virus seronegative participants. Ackerman, P; Chang, M; Llamoso, C; Lubin, S; Magee, M; Moore, K; Myers, E; Sevinsky, H, 2019)	1.96
" Opioid pharmacodynamic scores were similar with and without MET/BUP with no symptoms of withdrawal/overdose; no new safety signal for FTR when combined with a stable opioid regimen."	( Methadone and buprenorphine pharmacokinetics and pharmacodynamics when coadministered with fostemsavir to opioid-dependent, human immunodeficiency virus seronegative participants. Ackerman, P; Chang, M; Llamoso, C; Lubin, S; Magee, M; Moore, K; Myers, E; Sevinsky, H, 2019)	1.96
" For doravirine and methadone pharmacokinetic analysis, blood samples were collected before dosing through 24 hours after dosing."	( Evaluation of the Pharmacokinetic Interaction Between Doravirine and Methadone. Bouhajib, M; Fan, L; Iwamoto, M; Khalilieh, S; Sanchez, RI; Searle, S; Vaynshteyn, K; Yee, KL, 2020)	1.12
"This study applied pharmacokinetic modelling using virtual clinical trials, to pharmacokinetically quantify the extent and impact of rifampicin-mediated drug-drug interactions (DDI) on methadone plasma concentrations."	( The optimization of methadone dosing whilst treating with rifampicin: A pharmacokinetic modeling study. Al Zabit, D; Badhan, RKS; Gittins, R, 2019)	1.03
" It exhibits high pharmacokinetic (PK) variability."	( Utilizing Pediatric Physiologically Based Pharmacokinetic Models to Examine Factors That Contribute to Methadone Pharmacokinetic Variability in Neonatal Abstinence Syndrome Patients. Akinbi, H; Butler, D; Emoto, C; Fukuda, T; McPhail, BT; Vinks, AA; Wiles, JR, 2020)	0.77
" Blood samples were collected for pharmacokinetic analysis, and rectal temperature and sedation were assessed to evaluate opioid effects at predetermined times up to 24 hours after treatment."	( Pharmacokinetics and pharmacodynamics of a novel analgesic with a deterrent to human opioid abuse (methadone-fluconazole-naltrexone) after oral administration in dogs. Joo, H; KuKanich, B; KuKanich, K; Locuson, CW; Rankin, DC, 2020)	0.77
"To evaluate the pharmacokinetics and selected pharmacodynamic effects of a commercially available l-methadone/fenpipramide combination administered to isoflurane anaesthetized ponies."	( Pharmacokinetics and pharmacodynamics of l-methadone in isoflurane-anaesthetized and mechanically ventilated ponies. Braun, C; Gittel, C; Larenza Menzies, MP; Sandbaumhüter, FA; Schulz-Kornas, E; Theurillat, R; Thormann, W; Vervuert, I, 2021)	1.1
" Elimination half-life was 177 minutes, and maximum plasma concentration after IM administration was 950 ng/mL."	( Pharmacokinetics and pharmacodynamics of methadone administered intravenously and intramuscularly to isoflurane-anesthetized chickens. Barletta, M; Escobar, A; Gordon, J; Pypendop, BH; Quandt, JE; Sakai, DM, 2021)	0.89
"This study applied a pharmacokinetic modeling approach to examine gestational changes in R- and S-methadone concentrations in maternal plasma and fetal (cord) blood."	( Precision dosing of methadone during pregnancy: A pharmacokinetics virtual clinical trials study. Badhan, RKS; Gittins, R, 2021)	1.16
" Additionally, the R and S enantiomers of methadone have unique PK and pharmacodynamic properties."	( Pharmacokinetic modeling of R and S-Methadone and their metabolites to study the effects of various covariates in post-operative children. Aruldhas, BW; Gao, H; Heathman, MA; Ly, RC; Masters, AR; Overholser, BR; Packiasabapathy, S; Quinney, SK; Sadhasivam, S, 2021)	1.16
" A linear one-compartment population pharmacokinetic model with first-order conditional estimation with interaction was used to evaluate methadone clearance (CL/F) and volume of distribution (V/F)."	( Effect of HIV, antiretrovirals, and genetics on methadone pharmacokinetics: Results from the methadone antiretroviral pharmacokinetics study. Bart, G; Brundage, RC; Giang, LM; Hodges, JS; Yen, H, 2021)	1.08
" However, pharmacokinetic studies in children with obesity are challenging to conduct, so there is limited information to guide fentanyl and methadone dosing in these children."	( Use of physiologically-based pharmacokinetic modeling to inform dosing of the opioid analgesics fentanyl and methadone in children with obesity. Al-Uzri, A; Atz, AM; Carreño, FO; Delmore, P; Edginton, AN; Ford, JL; Gerhart, JG; Gonzalez, D; Muller, WJ; Perrin, EM; Watt, KM, 2022)	1.14

Compound-Compound Interactions

Medetomidine combined with methadone for premedication prior to neutering in healthy cats provided adequate analgesia for the first 6 h after administration with no adverse effects. Drug-drug interactions of potential clinical relevance are most likely to occur between opioid-replacement therapy and ARVs.

Excerpt	Reference	Relevance
"This paper presents 14 cases in which the distribution of barbiturates and the hydroxylated metabolites in combination with miscellaneous CNS-active drugs was studied."	( The human distribution of some barbiturate sedatives in combination with miscellaneous CNS-active drugs. McDowall, RD; Robinson, AE, )	0.13
" In combination with D-Phe, a dose of morphine less by half compared to its unique use does not reduce analgesic activity in rats, but after six weeks of treatment some undesirable side effects like dependence, behavioural disorders and growth retardation are markedly lowered."	( [The analgesic action of d-phenylalanine in combination with morphine or methadone]. Dove, B; Göres, E; Morgenstern, E, 1991)	0.51
"Published data confirm the substantial presence of alcohol in combination with cocaine, heroin and methadone among ME cases."	( Alcohol use in combination with cocaine, heroin and methadone by medical examiner cases. Dufour, MC; Haberman, PW; Noble, JA, 1995)	0.76
" Until the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), there was little information available on how common drugs interact with anti-HIV treatments."	( Drug interactions studied at ICAAC. Gaylord, G, 1999)	0.3
" This study compared completion rates for isoniazid (INH) preventive therapy for injection drug users (IDUs) randomly assigned to methadone treatment combined with directly observed preventive treatment (DOPT) versus those assigned to routine TB clinic referral without methadone treatment."	( A controlled trial of methadone treatment combined with directly observed isoniazid for tuberculosis prevention in injection drug users. Batki, SL; Bradley, JM; Bradley, M; Delucchi, K; Gruber, VA, 2002)	0.83
" The effects of this compound are probably more favorable when combined with a psychosocial intervention such as the Community Reinforcement Approach (CRA)."	( Experiences with an outpatient relapse program (community reinforcement approach) combined with naltrexone in the treatment of opioid-dependence: effect on addictive behaviors and the predictive value of psychiatric comorbidity. Kerkhof, AJ; Roozen, HG; van den Brink, W, 2003)	0.32
" To have any understanding of drug-drug interactions in HIV treatment we need to appreciate the importance of key pharmacological areas including: 1) how each drug in a regimen is eliminated; 2) the potential for a drug to either induce or inhibit metabolic enzymes and/or transporters; 3) the therapeutic index of each drug."	( Pharmacokinetic drug interactions with nevirapine. Back, D; Gibbons, S; Khoo, S, 2003)	0.32
" Methadone has significant, adverse drug-drug interactions with many antiretroviral therapeutic agents that can contribute to nonadherence and poor clinical outcomes in this high-risk population."	( Treatment of opioid dependence and coinfection with HIV and hepatitis C virus in opioid-dependent patients: the importance of drug interactions between opioids and antiretroviral agents. McCance-Katz, EF, 2005)	1.24
"To evaluate the effects of methadone, administered alone or in combination with acepromazine or xylazine, on sedation and on physiologic values in dogs."	( Effects of methadone, alone or in combination with acepromazine or xylazine, on sedation and physiologic values in dogs. Bettini, CM; Campagnol, D; Choma, JC; Figueroa, CD; Monteiro, ER, 2008)	1.03
" In all treatments body temperature decreased, this effect being more pronounced in dogs receiving methadone alone or in combination with acepromazine."	( Effects of methadone, alone or in combination with acepromazine or xylazine, on sedation and physiologic values in dogs. Bettini, CM; Campagnol, D; Choma, JC; Figueroa, CD; Monteiro, ER, 2008)	0.95
" Greater sedation was achieved when methadone was used in combination with acepromazine or xylazine."	( Effects of methadone, alone or in combination with acepromazine or xylazine, on sedation and physiologic values in dogs. Bettini, CM; Campagnol, D; Choma, JC; Figueroa, CD; Monteiro, ER, 2008)	1.01
"This review extends a prior meta-analysis of acupuncture's utility for treating opioid detoxification, addressing the efficacy of acupuncture when combined with allopathic therapies."	( A meta-analysis of acupuncture combined with opioid receptor agonists for treatment of opiate-withdrawal symptoms. Bao, YP; Epstein, DH; Liu, TT; Lu, L; Shi, J, 2009)	0.35
"To compare the effects of morphine (MOR), methadone (MET), butorphanol (BUT) and tramadol (TRA), in combination with acepromazine, on sedation, cardiorespiratory variables, body temperature and incidence of emesis in dogs."	( Comparative study on the sedative effects of morphine, methadone, butorphanol or tramadol, in combination with acepromazine, in dogs. Assis, HM; Campagnol, D; Junior, AR; Monteiro, ER; Quitzan, JG, 2009)	0.86
"We describe the first case of stress cardiomyopathy secondary to a drug-drug interaction."	( First case of stress cardiomyopathy as a result of methadone withdrawal secondary to drug-drug interaction. Lemesle, F; Nicola, W; Pierre Jonville-Béra, A, 2010)	0.61
" Thus, in vitro-in vivo extrapolation approaches were used to identify potential drug-drug interactions arising from inhibition of COD glucuronidation in humans."	( In vitro-in vivo extrapolation predicts drug-drug interactions arising from inhibition of codeine glucuronidation by dextropropoxyphene, fluconazole, ketoconazole, and methadone in humans. Elliot, DJ; Janchawee, B; Miners, JO; Raungrut, P; Somogyi, AA; Uchaipichat, V, 2010)	0.56
"Potential drug-drug interactions (PDDIs) might expand with new combination antiretroviral therapies (ART) and polypharmacy related to increasing age and comorbidities."	( Prevalence of comedications and effect of potential drug-drug interactions in the Swiss HIV Cohort Study. Back, D; Battegay, M; Bernasconi, E; Calmy, A; Cavassini, M; Chave, JP; Elzi, L; Furrer, H; Fux, C; Gibbons, S; Khoo, S; Ledergerber, B; Marzolini, C; Vernazza, P; Weber, R, 2010)	0.36
"To compare the use of co-medication, the potential drug-drug interactions (PDDIs) and the effect on antiretroviral therapy (ART) tolerability and efficacy in HIV-infected individuals according to age, ≥ 50 years or <50 years."	( Ageing with HIV: medication use and risk for potential drug-drug interactions. Back, D; Battegay, M; Bernasconi, E; Calmy, A; Cavassini, M; Elzi, L; Furrer, H; Khoo, S; Marzolini, C; Vernazza, P; Weber, R, 2011)	0.37
" Methadone users often have comorbidities and are prescribed drugs that may interact with methadone."	( Methadone: a review of drug-drug and pathophysiological interactions. Chibber, T; Hutson, JR; Kapur, BM; Luk, A; Selby, P, )	2.48
" Clinically significant MDIs included withdrawal symptoms, which were found among MMTP patients co-administered with buprenorphine or tramadol; severe QTc prolongation effect, which might be associated with use of haloperidol or droperidol; and additive CNS and respiratory depression, which could result from use of methadone in combination with chlorpromazine or thioridazine."	( Survey of methadone-drug interactions among patients of methadone maintenance treatment program in Taiwan. Lee, HY; Li, JH; Tang, HP; Wu, JS; Wu, LT; Yen, CF, 2012)	0.95
"To investigate the safety, sedative and analgesic properties of methadone in combination with acepromazine prior to neutering in cats."	( Methadone in combination with acepromazine as premedication prior to neutering in the cat. Bortolami, E; Murrell, JC; Slingsby, LS, 2013)	2.07
"Cats received one of three opioids combined with acepromazine (0."	( Methadone in combination with acepromazine as premedication prior to neutering in the cat. Bortolami, E; Murrell, JC; Slingsby, LS, 2013)	1.83
"Methadone provided comparable sedation and analgesia to both buprenorphine and butorphanol when combined with acepromazine."	( Methadone in combination with acepromazine as premedication prior to neutering in the cat. Bortolami, E; Murrell, JC; Slingsby, LS, 2013)	3.28
" Drug-drug interactions associated with this polypharmacy are relatively new to the field of HCV pharmacotherapy."	( Clinical management of drug-drug interactions in HCV therapy: challenges and solutions. Back, D; Buggisch, P; Burger, D; Buti, M; Craxí, A; Foster, G; Klinker, H; Larrey, D; Nikitin, I; Pol, S; Puoti, M; Romero-Gómez, M; Wedemeyer, H; Zeuzem, S, 2013)	0.39
"To compare the cardiopulmonary effects and the quality of anesthesia of the extradural lidocaine in combination with fentanyl or morphine in bitches undergoing ovariohysterectomy."	( Extradural anesthesia with lidocaine combined with fentanyl or methadone to ovariohisterectomy in dogs. Bernardi, CA; Cassu, RN; Diniz, MS; Kanashiro, GP; Nicácio, GM, 2013)	0.63
"The extradural lidocaine in combination with fentanyl or morphine allowed cardiopulmonary stability, however sufficient sensitive blockade was not provided in 100% of the dogs."	( Extradural anesthesia with lidocaine combined with fentanyl or methadone to ovariohisterectomy in dogs. Bernardi, CA; Cassu, RN; Diniz, MS; Kanashiro, GP; Nicácio, GM, 2013)	0.63
"In this study, solvent bar microextraction combined with gas chromatography-flame ionization detector (GC-FID) was used for preconcentration and determination of methadone in human body fluids."	( Optimization of solvent bar microextraction combined with gas chromatography for preconcentration and determination of methadone in human urine and plasma samples. Asgharinezhad, AA; Ebrahimzadeh, H; Mirbabaei, F; Mollazadeh, N; Shekari, N, 2014)	0.81
"To evaluate the cardiorespiratory, sedative and antinociceptive effects of dexmedetomidine alone or in combination with methadone, morphine or tramadol in dogs."	( Cardiorespiratory, sedative and antinociceptive effects of dexmedetomidine alone or in combination with methadone, morphine or tramadol in dogs. Cardoso, CG; da Silva, TH; de Mattos-Junior, E; Marques, DR, 2014)	0.83
"Low dose tiletamine-zolazepam combined with methadone provided superior sedation to ACE."	( A comparison of low dose tiletamine-zolazepam or acepromazine combined with methadone for pre-anaesthetic medication in cats. Kloeppel, H; Mair, A; Ticehurst, K, 2014)	0.89
"The aim of the study was to evaluate the tolerability, sedative and analgesic effects of methadone in combination with medetomidine for premedication prior to neutering in healthy cats."	( Methadone in combination with medetomidine as premedication prior to ovariohysterectomy and castration in the cat. Bortolami, E; Murrell, JC; Slingsby, LS, 2015)	2.08
"Medetomidine combined with methadone for premedication prior to neutering in healthy cats provided adequate analgesia for the first 6 h after administration with no adverse effects; effects overall were comparable with medetomidine combined with buprenorphine or butorphanol."	( Methadone in combination with medetomidine as premedication prior to ovariohysterectomy and castration in the cat. Bortolami, E; Murrell, JC; Slingsby, LS, 2015)	2.16
"To compare the sedative effects of an intramuscular (IM) low dose of medetomidine in combination with butorphanol or methadone in dogs."	( The sedative effects of intramuscular low-dose medetomidine in combination with butorphanol or methadone in dogs. Canfrán, S; Costa-Farré, C; Gómez de Segura, IA; Puighibet, Z; Santos, L, 2015)	0.84
"To describe potential drug-drug interactions in the area of HIV/hepatitis C virus (HCV) coinfection and injection drug use, including those between antiretrovirals (ARVs), direct-acting antivirals (DAAs), and opioid-agonist therapy, and to supply a practical approach to their management."	( Drug-Drug Interactions With Antiviral Agents in People Who Inject Drugs Requiring Substitution Therapy. Christensen, S; Gillessen, A; Hanhoff, N; Meemken, L; Tseng, A, 2015)	0.42
"We used the following search terms: pharmacokinetic and pharmacodynamic drug-drug interaction, opioid substitution, HIV, hepatitis and the individual names of the relevant agents of the following drug classes and the drug classes itself: reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, protease inhibitors, direct-acting antivirals, opioide, benzodiazepines, anticonvulsants, antidepressants and antipsychotics."	( Drug-Drug Interactions With Antiviral Agents in People Who Inject Drugs Requiring Substitution Therapy. Christensen, S; Gillessen, A; Hanhoff, N; Meemken, L; Tseng, A, 2015)	0.42
"Pharmacokinetic data were available for all ARVs and DAAs except rilpivirine, indinavir, saquinavir, maraviroc, dolutegravir, and MK-8742 with buprenorphine as well as maraviroc with methadone Drug-drug interactions of potential clinical relevance are most likely to occur between opioid-replacement therapy and ARVs, particularly the nonnucleoside reverse transcriptase inhibitors, efavirenz and nevirapine, and HIV protease inhibitors."	( Drug-Drug Interactions With Antiviral Agents in People Who Inject Drugs Requiring Substitution Therapy. Christensen, S; Gillessen, A; Hanhoff, N; Meemken, L; Tseng, A, 2015)	0.61
" ARV and DAAs may interact with other drug classes commonly used in the opioid-dependent population, including benzodiazepines, antidepressants, anticonvulsants, and antipsychotics."	( Drug-Drug Interactions With Antiviral Agents in People Who Inject Drugs Requiring Substitution Therapy. Christensen, S; Gillessen, A; Hanhoff, N; Meemken, L; Tseng, A, 2015)	0.42
" Daclatasvir is a potent pangenotypic inhibitor of the HCV NS5A replication complex recently approved for HCV treatment in Europe and Japan in combination with other antivirals."	( Assessment of drug-drug interactions between daclatasvir and methadone or buprenorphine-naloxone. Bertz, R; Bifano, M; Bruce, RD; DeMicco, M; Garimella, T; Hwang, C; Kandoussi, H; Luo, WL; Wang, R; Wastall, P, 2015)	0.66
"To evaluate the antinociceptive effects of intravenous methadone combined with detomidine or acepromazine in adult horses."	( Antinociceptive effects of methadone combined with detomidine or acepromazine in horses. Crosignani, N; Lopes, C; Luna, SP; Pantoja, JC; Puoli, JN; Quarterone, C; Rosa, AC; Taylor, PM, 2016)	0.98
"To evaluate the cardiopulmonary and sedative effects of xylazine alone or in combination with methadone, morphine or tramadol in sheep."	( Sedative and cardiopulmonary effects of xylazine alone or in combination with methadone, morphine or tramadol in sheep. Auckburally, A; Borges, LP; Cerejo, SA; de Carvalho, LL; de Mattos-Junior, E; Nishimura, LT; Villela, IO, 2016)	0.88
" Each drug combination was mixed in the syringe and injected intravenously."	( Sedative and cardiopulmonary effects of xylazine alone or in combination with methadone, morphine or tramadol in sheep. Auckburally, A; Borges, LP; Cerejo, SA; de Carvalho, LL; de Mattos-Junior, E; Nishimura, LT; Villela, IO, 2016)	0.66
"Objectives The aim of the study was to evaluate the effectiveness of epidural lidocaine in combination with either methadone or morphine for postoperative analgesia in cats undergoing ovariohysterectomy."	( Postoperative pain control in cats: clinical trials with pre-emptive lidocaine epidural co-administered with morphine or methadone. de Andrade Bicudo, N; de Assis, KT; DeRossi, R; Hermeto, LC; Jardim, PHA, 2016)	0.85
"The objectives of this study were to determine: (1) the sedative effects of dexmedetomidine in combination with methadone, midazolam, or both, and (2) the propofol dose required to achieve endotracheal intubation in healthy dogs."	( Comparison of sedation scores and propofol induction doses in dogs after intramuscular administration of dexmedetomidine alone or in combination with methadone, midazolam, or methadone plus midazolam. Bustamante, R; Canfrán, S; Cediel, R; de Segura, IA; González, P; Re, M, 2016)	0.84
"To evaluate the sedative and cardiopulmonary effects of three methadone doses, combined with acepromazine, in dogs."	( Effects of three methadone doses combined with acepromazine on sedation and some cardiopulmonary variables in dogs. Bitti, FS; Campagnol, D; Loureiro, B; Monteiro, ER; Nunes Junior, JS; Rangel, JP, 2017)	1.04
" We evaluated the safety and tolerance of additional use of D,L-methadone in patients with glioma in combination with chemotherapy."	( Safety and Tolerance of D,L-Methadone in Combination with Chemotherapy in Patients with Glioma. Friesen, C; Misch, M; Onken, J; Vajkoczy, P, 2017)	0.99
"D,L-methadone can be safely combined with standard glioma chemotherapy without increasing the risk of toxicity or vegetative symptoms such as tachycardia, sweating and restlessness."	( Safety and Tolerance of D,L-Methadone in Combination with Chemotherapy in Patients with Glioma. Friesen, C; Misch, M; Onken, J; Vajkoczy, P, 2017)	1.31
"Our primary objective was test the hypothesis that oral methadone combined with oral ketamine is more effective than oral methadone or ketamine alone in reducing neuropathic pain."	( Management of Neuropathic Chronic Pain with Methadone Combined with Ketamine: A Randomized, Double Blind, Active-Controlled Clinical Trial. Caumo, W; Dalmolin, GD; Ferreira, J; Godoy, MC; Menezes, MS; Rigo, FK; Rossato, MF; Silva, MA; Trevisan, G, 2017)	0.96
" Changes in PO deaths in combination with other psychoactive substances may provide a partial explanation."	( Increases from 2002 to 2015 in prescription opioid overdose deaths in combination with other substances. Griesler, P; Hu, MC; Kandel, DB; Wall, M, 2017)	0.46
" We calculated (1) changes in proportions of deaths in combination with benzodiazepines, antidepressants, heroin, alcohol, cocaine between the two periods, and (2) proportions of increase in deaths attributable to each substance among PO and synthetic opioids other than methadone (SO-M) deaths, by age, gender, race/ethnicity."	( Increases from 2002 to 2015 in prescription opioid overdose deaths in combination with other substances. Griesler, P; Hu, MC; Kandel, DB; Wall, M, 2017)	0.63
" The largest increases occurred in combination with heroin among all PO (4."	( Increases from 2002 to 2015 in prescription opioid overdose deaths in combination with other substances. Griesler, P; Hu, MC; Kandel, DB; Wall, M, 2017)	0.46
"Increased PO overdose deaths over the last decade may be partially explained by increased deaths in combination with other psychoactive substances."	( Increases from 2002 to 2015 in prescription opioid overdose deaths in combination with other substances. Griesler, P; Hu, MC; Kandel, DB; Wall, M, 2017)	0.46
" Solutions containing mixtures of methadone combined with acepromazine, medetomidine or xylazine were stored in syringes at 25°C/60%RH."	( Chemical stability of morphine and methadone, and of methadone in combination with acepromazine, medetomidine or xylazine, during prolonged storage in syringes. Lee, DY; Watson, N; Whittem, T, 2017)	1.01
" When in combination with acepromazine or xylazine, methadone also remained chemically stable, but the combination with medetomidine failed stability criteria prior to 6 months."	( Chemical stability of morphine and methadone, and of methadone in combination with acepromazine, medetomidine or xylazine, during prolonged storage in syringes. Lee, DY; Watson, N; Whittem, T, 2017)	0.98
" Subjects received methadone (arm 1) or buprenorphine-naloxone (arm 2) once daily (QD) per their existing individual prescriptions alone (days 1 to 9) and then in combination with glecaprevir at 300 mg QD and pibrentasvir at 120 mg QD (days 10 to 16) each morning."	( No Clinically Relevant Drug-Drug Interactions between Methadone or Buprenorphine-Naloxone and Antiviral Combination Glecaprevir and Pibrentasvir. Asatryan, A; Geoffroy, P; Kort, J; Kosloski, MP; Liu, W; Zhao, W, 2017)	1.03
"OBJECTIVE To evaluate cardiopulmonary, sedative, and antinociceptive effects of dexmedetomidine combined with commonly administered opioids in dogs."	( Effects of dexmedetomidine combined with commonly administered opioids on clinical variables in dogs. Auckburally, A; de Mattos-Junior, E; Garcia, DO; Honsho, CS; Nishimura, LT; Santilli, J; Vieira, BHB, 2018)	0.48
"Opioids can be combined with alpha-2-adrenoreceptor agonists to sedate dogs for radiography."	( Comparison of sedation in dogs: methadone or butorphanol in combination with dexmedetomidine intravenously. Bhalla, RJ; Leece, EA; Trimble, T, 2018)	0.76
"IV butorphanol provides more effective sedation at 10 minutes than methadone, in combination with dexmedetomidine."	( Comparison of sedation in dogs: methadone or butorphanol in combination with dexmedetomidine intravenously. Bhalla, RJ; Leece, EA; Trimble, T, 2018)	1
" The aim of this work is to leverage knowledge from drug-drug interaction (DDI) studies in new drug applications between methadone and antiviral medications to better understand methadone disposition and to inform design of future DDI studies with methadone."	( Drug-Drug Interaction Studies of Methadone and Antiviral Drugs: Lessons Learned. Lakota, EA; Patel, V; Sahajwalla, CG; Volpe, DA; Xu, Y; Younis, IR, 2019)	1
" Opioid pharmacodynamic scores were similar with and without MET/BUP with no symptoms of withdrawal/overdose; no new safety signal for FTR when combined with a stable opioid regimen."	( Methadone and buprenorphine pharmacokinetics and pharmacodynamics when coadministered with fostemsavir to opioid-dependent, human immunodeficiency virus seronegative participants. Ackerman, P; Chang, M; Llamoso, C; Lubin, S; Magee, M; Moore, K; Myers, E; Sevinsky, H, 2019)	1.96
" FTR can be administered with MET or BUP without dose adjustment."	( Methadone and buprenorphine pharmacokinetics and pharmacodynamics when coadministered with fostemsavir to opioid-dependent, human immunodeficiency virus seronegative participants. Ackerman, P; Chang, M; Llamoso, C; Lubin, S; Magee, M; Moore, K; Myers, E; Sevinsky, H, 2019)	1.96
"The aim of this study was to compare the effects of methadone combined with detomidine or acepromazine on the quality of sedation and its influence over dissociative anesthesia in healthy horses."	( Effect of Methadone Combined With Acepromazine or Detomidine on Sedation and Dissociative Anesthesia in Healthy Horses. Alonso, BB; Bisetto, SP; Carregaro, AB; Censoni, JB; Reginato, GM; Ueda, GI, 2020)	1.21
"To compare the propofol infusion rate and cardiopulmonary effects during total intravenous anesthesia with propofol alone and propofol combined with methadone, fentanyl or nalbuphine in domestic chickens undergoing ulna osteotomy."	( Total intravenous anesthesia in domestic chicken (Gallus gallus domesticus) with propofol alone or in combination with methadone, nalbuphine or fentanyl for ulna osteotomy. Alievi, MM; Boos, MZ; Gutierrez, LG; Herrera, JR; Mombach, VS; Monteiro, ER; Santos, EA, 2020)	0.97
" This case report illustrates the potential for cannabidiol to interact with stable medication regimens."	( Clinically Significant Drug-Drug Interaction Between Methadone and Cannabidiol. Bruera, E; Madden, K; Tanco, K, 2020)	0.81
" Therefore, we analyzed the cytotoxic effect of methadone alone and in combination with temozolomide, a DNA-alkylating drug that is first-line used in GBM treatment, utilizing GBM-derived cell lines and a human fibroblast cell line."	( Cytotoxic and Senolytic Effects of Methadone in Combination with Temozolomide in Glioblastoma Cells. Beltzig, L; Haas, B; Kaina, B; Piee-Staffa, A, 2020)	1.09
"To evaluate the feasibility of gastroduodenoscopy in dogs premedicated with acepromazine in combination with butorphanol or methadone."	( Comparison of the effects of methadone and butorphanol combined with acepromazine for canine gastroduodenoscopy. Candido, MV; Casoni, D; Lepajoe, J; Salla, KM; Spillmann, T, 2020)	1.06
"In our study population, the effects of methadone and butorphanol when combined with acepromazine were comparable."	( Comparison of the effects of methadone and butorphanol combined with acepromazine for canine gastroduodenoscopy. Candido, MV; Casoni, D; Lepajoe, J; Salla, KM; Spillmann, T, 2020)	1.12
" We systematically searched for studies of acute toxicity of quetiapine or other antipsychotics combined with morphine or methadone."	( Quetiapine and other antipsychotics combined with opioids in legal autopsy cases: A random finding or cause of fatal outcome? Andersen, CU; Andersen, FD; Simonsen, U, 2021)	0.83
"To compare dexmedetomidine with acepromazine for premedication combined with methadone in dogs undergoing brachycephalic obstructive airway syndrome (BOAS) surgery."	( Comparison between dexmedetomidine and acepromazine in combination with methadone for premedication in brachycephalic dogs undergoing surgery for brachycephalic obstructive airway syndrome. Auckburally, A; Flaherty, D; Murison, PJ; Petruccione, I, 2021)	1.08
"To evaluate the effect of methadone maintenance treatment (MMT) combined with rilpivirine (RPV)-based regimens on drug use of HIV individuals."	( Outcomes of Methadone Maintenance Therapy Combined with Rilpivirine/Efavirenz in Treatment-Naive HIV-Infected Patients. Dong, X; Hong, L; Huang, S; Lei, S; Li, H; Li, X; Xie, R; Xin, J; Yang, C; Yang, X; Zhang, B; Zhang, R, 2021)	1.3
"This study was a prospective, open-label, controlled, drug-drug interaction trial at a single center for 24 weeks."	( Outcomes of Methadone Maintenance Therapy Combined with Rilpivirine/Efavirenz in Treatment-Naive HIV-Infected Patients. Dong, X; Hong, L; Huang, S; Lei, S; Li, H; Li, X; Xie, R; Xin, J; Yang, C; Yang, X; Zhang, B; Zhang, R, 2021)	1
"To evaluate the sedative, analgesic and recovery characteristics of two subanaesthetic ketamine doses in combination with dexmedetomidine and methadone for intramuscular sedation in healthy Beagles."	( Sedative and analgesic effects of two subanaesthetic doses of ketamine in combination with methadone and a low dose of dexmedetomidine in healthy dogs. Aguado, D; Arenillas, M; Canfrán, S; Gómez de Segura, IA, 2021)	1.04
"To evaluate the efficacy of a perineural injection of dexmedetomidine combined with ropivacaine for reducing postoperative methadone requirements in dogs after tibial plateau levelling osteotomy (TPLO)."	( Effects of perineural dexmedetomidine combined with ropivacaine on postoperative methadone requirements in dogs after tibial plateau levelling osteotomy: a two-centre study. Marolf, V; Picavet, P; Sandersen, C; Selz, J; Spadavecchia, C; Tutunaru, A, 2022)	1.15
"Perineural dexmedetomidine combined with ropivacaine did not reduce postoperative methadone requirements in dogs after TPLO, but results may differ from one centre to another."	( Effects of perineural dexmedetomidine combined with ropivacaine on postoperative methadone requirements in dogs after tibial plateau levelling osteotomy: a two-centre study. Marolf, V; Picavet, P; Sandersen, C; Selz, J; Spadavecchia, C; Tutunaru, A, 2022)	1.17
"Methadone and buprenorphine have pharmacologic properties that are concerning for a high risk of drug-drug interactions (DDIs)."	( Identifying Clinically Relevant Drug-Drug Interactions With Methadone and Buprenorphine: A Translational Approach to Signal Detection. Acton, EK; Bilker, WB; Brensinger, CM; Dawwas, GK; Hennessy, S; Leonard, CE; Li, L; Miano, TA; Neuman, M; Nguyen, TPP; Soprano, SE; Wang, L; Woody, G; Yu, E, 2022)	2.41
"The aim of this study was to evaluate the latency, extent of analgesia, and duration of motor block of levobupivacaine alone and combined with methadone or dexmedetomidine after epidural administration during and after mastectomy in dogs."	( Analgesic, cardiorespiratory effects and motor block characteristics of epidural levobupivacaine alone or in combination with methadone or dexmedetomidine in bitches undergoing unilateral total mastectomy. Albuquerque, VB; Barbosa, CF; Caramalac, SM; Frazílio, FO; Jardim, PHA; Oliveira, AR, 2022)	1.13

Bioavailability

Methadone has a mean bioavailability of around 75% (range 36-100%). A scoping review was performed to evaluate whether existing literature on methadone bioavailability in human subjects support the current recommendation.

Excerpt	Reference	Relevance
" No significant differences were found between the control and methadone groups for ZDV bioavailability or Tmax, serum half-life, glucuronidation, or urinary excretion."	( Pharmacokinetic interactions of zidovudine and methadone in intravenous drug-using patients with HIV infection. Brechbühl, AB; Friedland, GH; Kahl, P; Miller, MA; Schwartz, EL; Selwyn, PA, 1992)	0.78
" First-pass glucuronidation limits systemic bioavailability of oral naloxone."	( Treatment of opioid-induced constipation with oral naloxone: a pilot study. Culpepper-Morgan, JA; Foley, K; Houde, RW; Inturrisi, CE; Kreek, MJ; Marsh, F; Portenoy, RK, 1992)	0.28
" In one patient, a higher level of d-methadone in plasma was caused by both faster elimination and lower bioavailability of l-methadone."	( Chiral analysis of methadone in plasma by high-performance liquid chromatography. Beck, O; Boreus, LO; Jacobsson, G; Lafolie, P, 1991)	0.88
" It has the following pharmacokinetic properties: high lipophilicity, large volume of distribution (initial and steady state), low clearance (hepatic capacity limited) with a long terminal elimination time, high bioavailability following oral administration, and a tendency to accumulate in the blood and tissues."	( [Methadone--pharmacokinetics and pharmacodynamics of an opiate]. Jage, J, 1989)	1.19
" The oral bioavailability is approximately 40% with marked patient-to-patient variations as a result of differences in presystemic elimination."	( High-dose morphine and methadone in cancer patients. Clinical pharmacokinetic considerations of oral treatment. Säwe, J, )	0.44
" There were pronounced differences in oral bioavailability between the two opioids: methadone, 79 +/- 11."	( A comparative study of the efficacy and pharmacokinetics of oral methadone and morphine in the treatment of severe pain in patients with cancer. Cherry, DA; Cousins, MJ; Gourlay, GK, 1986)	0.73
" Most steroids were readily absorbed and their bioavailability after intravaginal instillation was greater than after oral administration because of a reduced first-pass effect."	( Absorption from the vagina. Benziger, DP; Edelson, J, 1983)	0.27
" The peak plasma concentration was only reached 3-4 h after administration, whereas the relative bioavailability up to 8 h after dosing ranged from 35-58%."	( Preliminary study on the absorption profile after rectal and oral administration of methadone in human volunteers. Fiets, G; Meijer, DK; Moolenaar, F; Visser, J, 1984)	0.49
" Bioavailability was determined by comprising the areas under the plasma concentration versus time curves of unlabelled and labelled methadone."	( Single dose pharmacokinetics and bioavailability of methadone in man studied with a stable isotope method. Anggård, E; Holmstrand, J; Meresaar, U; Nilsson, MI, 1981)	0.72
" However, because of high interpersonal variation in bioavailability and the long duration of action of this drug, treatments should be highly personalized."	( Respiratory depression in a patient receiving oral methadone for cancer pain. Bruera, E; Hunt, G, 1995)	0.54
" The switch to oral agents must take into consideration the differences in potency, half-life, and oral bioavailability between the agents."	( Outpatient therapy of iatrogenic drug dependency following prolonged sedation in the pediatric intensive care unit. Deshpande, JK; Gregory, DF; Tobias, JD, 1994)	0.29
" However, the lagtime after oral administration and the bioavailability did not show differences between the isomers."	( Stereoselective pharmacokinetics of methadone in chronic pain patients. Angelo, HR; Blemmer, T; Christrup, LL; Drenck, NE; Kristensen, K; Rasmussen, SN; Sjøgren, P, 1996)	0.57
" The relationship between drug effect and the systemic bioavailability of methadone, measured as the area under the plasma concentration-time curve (AUC0-180), was also evaluated."	( The effect of changes in gastric pH induced by omeprazole on the absorption and respiratory depression of methadone. Aguirre, C; Calvo, R; de Castro, J; Garrido, MJ; Gómez, E; Rodríguez-Sasiaín, JM, 1996)	0.74
" Future research has to better define the variation in both bioavailability and elimination of methadone in different patient populations, the interaction between methadone and the most commonly used drugs in cancer patients, the type and activity of potential methadone metabolites, and the equianalgesic doses between methadone and the most commonly used opioids."	( An update on the clinical use of methadone for cancer pain. Bruera, E; Ripamonti, C; Zecca, E, 1997)	0.8
"15 l kg-1 day-1 and a bioavailability of 100% was 17."	( Methadone distribution and excretion into breast milk of clients in a methadone maintenance programme. Dusci, LJ; Hackett, LP; Ilett, KF; Kristensen, JH; Wojnar-Horton, RE; Yapp, P, 1997)	1.74
" The mean l-methadone dose:l-methadone plasma concentration ratio, an index of the bioavailability of l-methadone in individual subjects, showed no significant change when the treatment was changed to d,l-methadone."	( L-Methadone and D,L-methadone in methadone maintenance treatment: a comparison of therapeutic effectiveness and plasma concentrations. de Vos, JW; Kaplan, CD; Krause, JK; Staib, AH; Tursch, M; Ufkes, JG; van Wilgenburg, H; Woodcock, BG, 1998)	1.4
" Intra- and inter-patient variations in methadone bioavailability have been observed after oral methadone treatment and this makes it difficult to predict a dosing regimen."	( The roles of P-glycoprotein and intracellular metabolism in the intestinal absorption of methadone: in vitro studies using the rat everted intestinal sac. Barthe, L; Bouër, R; Houin, G; Philibert, C; Tournaire, C; Woodley, J, 1999)	0.79
"Clinical trials carried out to compare methadone and buprenorphine in the treatment of opioid dependence have generally employed an alcoholic solution of buprenorphine, which has a bioavailability superior to that of the tablets."	( Buprenorphine: a controlled clinical trial in the treatment of opioid dependence. Gessa, GL; Maremmani, I; Pani, PP; Pirastu, R; Tagliamonte, A, 2000)	0.58
"The quantitative structure-bioavailability relationship of 232 structurally diverse drugs was studied to evaluate the feasibility of constructing a predictive model for the human oral bioavailability of prospective new medicinal agents."	( QSAR model for drug human oral bioavailability. Topliss, JG; Yoshida, F, 2000)	0.31
" Methadone release in vivo was estimated by deconvolution, F-PLGA giving a bioavailability >99% (methadone was totally released in 48h), while the estimated bioavailability of F-PLA was lower than expected."	( In vivo-in vitro study of biodegradable methadone delivery systems. Delgado, A; Evora, C; Llabrés, M; Negrin, CM, 2001)	1.49
"A study of patients taking ritonavir and methadone indicates that ritonavir lowers bioavailability of methadone by 30 to 40 percent."	( Ritonavir (Norvir) and methadone. , 1998)	0.88
" This may lead to increased bioavailability of coadministered compounds."	( Methadone inhibits rhodamine123 transport in Caco-2 cells. Greenblatt, DJ; Perloff, MD; Störmer, E; von Moltke, LL, 2001)	1.75
" Methadone may be an important alternative for those who have side effects related to the use of other opioids because it has no known active metabolites, is well absorbed by oral and rectal routes, and also has the advantage of very low cost."	( Methadone use in cancer patients with pain: a review. Bruera, E; Sweeney, C, 2002)	2.67
" Methadone has a mean bioavailability of around 75% (range 36-100%)."	( Interindividual variability of the clinical pharmacokinetics of methadone: implications for the treatment of opioid dependence. Baumann, P; Buclin, T; Eap, CB, 2002)	1.46
"Rectal administration of methadone may be an alternative to intravenous and oral dosing in cancer pain, but the bioavailability of the rectal route is not known."	( Bioavailabilities of rectal and oral methadone in healthy subjects. Dale, O; Kharasch, ED; Sheffels, P, 2004)	0.9
"Rectal administration of methadone results in rapid absorption, a high bioavailability and long duration of action."	( Bioavailabilities of rectal and oral methadone in healthy subjects. Dale, O; Kharasch, ED; Sheffels, P, 2004)	0.9
" The bioavailability was approximately 60%."	( Population pharmacokinetics of caffeine and its metabolites theobromine, paraxanthine and theophylline after inhalation in combination with diacetylmorphine. Beijnen, JH; de Jonge, ME; den Hoed, R; Hendriks, VM; Huitema, AD; Sparidans, RW; van den Brink, W; van Ree, JM; Zandvliet, AS, 2005)	0.33
"Methadone is an opioid, which has a high oral bioavailability (>70%) and a long elimination half-life (>20 h) in human beings."	( The effects of inhibiting cytochrome P450 3A, p-glycoprotein, and gastric acid secretion on the oral bioavailability of methadone in dogs. Aman, AM; Kukanich, B; Lascelles, BD; Mealey, KL; Papich, MG, 2005)	1.98
" Not much is known about the pharmacokinetics profile and bioavailability of this specific administration method."	( Pharmacokinetics and pharmacodynamics of high doses of pharmaceutically prepared heroin, by intravenous or by inhalation route in opioid-dependent patients. Beijnen, JH; Hendriks, VM; Hillebrand, MJ; Huitema, AD; Rook, EJ; van den Brink, W; van Ree, JM, 2006)	0.33
" However, it is not known if this is due to changes in bioavailability or if this phenomenon is stereoselective."	( Stereoselective quantification of methadone and a d(6)-labeled isotopomer using high performance liquid chromatography-atmospheric pressure chemical ionization mass-spectrometry: application to a pharmacokinetic study in a methadone maintained subject. Foster, DJ; Heinkele, G; Morton, EB; Mürdter, TE; Somogyi, AA, 2006)	0.61
" Its mean bioavailability is around 75%."	( [Methadone: from pharmacokinetic profile to clinical pharmacology]. Gury, C; Laqueille, X; Vazquez, V, )	1.04
"Valspodar increased methadone's bioavailability as consequence of P-gp inhibition, which resulted in an increased analgesic effect of methadone."	( Modeling methadone pharmacokinetics in rats in presence of P-glycoprotein inhibitor valspodar. Calvo, R; Ortega, I; Perez-Ruixo, JJ; Rodriguez, M; Suarez, E, 2007)	1.08
" Naloxone, an opiate antagonist, is very poorly absorbed with sublingual administration, but if it is injected intravenously, it will antagonise the effects of buprenorphine."	( Buprenorphine + naloxone: new combination. Opiate dependence: no proof of reduced risk of self-administered injection. , 2007)	0.34
"7), which approximates the bioavailability of the drug administered orally."	( Conversion from parenteral to oral methadone. Gómez-Batiste, X; González-Barboteo, J; Porta-Sales, J; Sánchez, D; Tuca, A, 2008)	0.62
" Methadone bioavailability was unchanged, despite inhibition of gastrointestinal P-glycoprotein activity, suggesting that this transporter does not limit methadone intestinal absorption."	( Methadone pharmacokinetics are independent of cytochrome P4503A (CYP3A) activity and gastrointestinal drug transport: insights from methadone interactions with ritonavir/indinavir. Bedynek, PS; Hoffer, C; Kharasch, ED; Walker, A; Whittington, D, 2009)	2.71
" Methadone bioavailability and P-glycoprotein activity were minimally affected."	( Methadone metabolism and clearance are induced by nelfinavir despite inhibition of cytochrome P4503A (CYP3A) activity. Bedynek, PS; Hoffer, C; Kharasch, ED; Walker, A; Whittington, D, 2009)	2.71
" Bioavailability was unchanged despite significant inhibition of intestinal P-glycoprotein."	( Mechanism of ritonavir changes in methadone pharmacokinetics and pharmacodynamics: I. Evidence against CYP3A mediation of methadone clearance. Bedynek, PS; Hoffer, C; Kharasch, ED; Park, S; Walker, A; Whittington, D, 2008)	0.63
"51 to 0); and increased bioavailability (from 37 to 95%)."	( Mechanism of ritonavir changes in methadone pharmacokinetics and pharmacodynamics: II. Ritonavir effects on CYP3A and P-glycoprotein activities. Bedynek, PS; Hoffer, C; Kharasch, ED; Walker, A; Whittington, D, 2008)	0.63
" Though oral transmucosal fentanyl citrate has reduced bioavailability (25%), it inherits potential for breakthrough pain management."	( Pediatric palliative care: use of opioids for the management of pain. Anderson, BJ; Craig, F; Michel, E; Zernikow, B, 2009)	0.35
"3 hours and bioavailability was 79 +/- 22%."	( Clinical pharmacology of methadone in dogs. Bondesson, U; Holgersson, A; Ingvast-Larsson, C; Lagerstedt, AS; Olsson, K, 2010)	0.66
"Oral bioavailability (F) is a product of fraction absorbed (Fa), fraction escaping gut-wall elimination (Fg), and fraction escaping hepatic elimination (Fh)."	( Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination. Chang, G; El-Kattan, A; Miller, HR; Obach, RS; Rotter, C; Steyn, SJ; Troutman, MD; Varma, MV, 2010)	0.36
"To characterize the bioavailability and pharmacokinetics of oral and injectable formulations of methadone after IV, oral, and intragastric administration in horses."	( Bioavailability and pharmacokinetics of oral and injectable formulations of methadone after intravenous, oral, and intragastric administration in horses. Barker, SA; Hosgood, GL; Keowen, ML; Linardi, RL; Short, CR; Stokes, AM, 2012)	0.83
" Oral pharmacokinetics in horses included a short half-life (approx 1 hour), high total body clearance corrected for bioavailability (5 to 8 mL/min/kg), and small apparent volume of distribution corrected for bioavailability (0."	( Bioavailability and pharmacokinetics of oral and injectable formulations of methadone after intravenous, oral, and intragastric administration in horses. Barker, SA; Hosgood, GL; Keowen, ML; Linardi, RL; Short, CR; Stokes, AM, 2012)	0.61
"Absorption of methadone in the small intestine in horses appeared to be limited owing to the low bioavailability after intragastric administration."	( Bioavailability and pharmacokinetics of oral and injectable formulations of methadone after intravenous, oral, and intragastric administration in horses. Barker, SA; Hosgood, GL; Keowen, ML; Linardi, RL; Short, CR; Stokes, AM, 2012)	0.97
" Bioavailability decreased."	( Mechanism of efavirenz influence on methadone pharmacokinetics and pharmacodynamics. Bedynek, PS; Campbell, S; Crafford, A; Ensign, D; Hoffer, C; Kharasch, ED; Kim, T; London, A; Stubbert, K; Whittington, D, 2012)	0.65
" It was unknown whether this newly developed formulation would affect its bioavailability compared with the currently available formulation of methadone."	( Pharmacokinetics of a new immediate-release methadone tablet formulation with decreased in vitro solubility. Vinson, RK, 2012)	0.84
"The objective of this study was to further examine the in vitro solubility of the new methadone formulation, and to evaluate and compare the relative bioavailability and pharmacokinetics to the previous reference formulation after a single oral dose administration under fasting conditions."	( Pharmacokinetics of a new immediate-release methadone tablet formulation with decreased in vitro solubility. Vinson, RK, 2012)	0.86
" Their impact on oral pharmacotherapy, including their effect on the bioavailability of oral medications, is poorly understood."	( Unpredictable absorption of oral opioid medications in a quadriplegic patient with chronic enterocutaneous fistulas. Viswesh, VV, 2012)	0.38
" After SC administration bioavailability was complete and the terminal half-life was 215 ± 84 min (mean ± SD), Tmax 31 ± 15 min and Cmax 45 ±11 ng/mL."	( Methadone in healthy goats - pharmacokinetics, behaviour and blood pressure. Bondesson, U; Hydbring-Sandberg, E; Ingvast-Larsson, C; Olsén, L; Olsson, K, 2013)	1.83
" This study characterized the bioavailability of these drugs following buccal administration to cats."	( Bioavailability of morphine, methadone, hydromorphone, and oxymorphone following buccal administration in cats. Ilkiw, JE; Pypendop, BH; Shilo-Benjamini, Y, 2014)	0.69
" Typical bioavailability after IM administration was 79%."	( Pharmacokinetics and pharmacodynamics of methadone administered intravenously and intramuscularly to isoflurane-anesthetized chickens. Barletta, M; Escobar, A; Gordon, J; Pypendop, BH; Quandt, JE; Sakai, DM, 2021)	0.89
"Disposition of methadone in isoflurane-anesthetized chickens was characterized by a large volume of distribution and moderate clearance, with high bioavailability after IM administration."	( Pharmacokinetics and pharmacodynamics of methadone administered intravenously and intramuscularly to isoflurane-anesthetized chickens. Barletta, M; Escobar, A; Gordon, J; Pypendop, BH; Quandt, JE; Sakai, DM, 2021)	1.24
" A scoping review was performed to evaluate whether existing literature on methadone bioavailability in human subjects support the current recommendation that an equivalent enteral dose is twice the intravenous dose."	( Methadone bioavailability and dose conversion implications with intravenous and enteral administration: A scoping review. Craig, WY; Fraser, GL; Kemp, HD; Liu, J; McKelvy, DJ; Nichols, SD; Riker, RR; Smith, KE, 2021)	2.29
"A librarian-assisted search of the PubMed and EMBASE databases identified all English-language articles with the terms methadone and bioavailability and/or conversion in the title or abstract published from inception though December 2019."	( Methadone bioavailability and dose conversion implications with intravenous and enteral administration: A scoping review. Craig, WY; Fraser, GL; Kemp, HD; Liu, J; McKelvy, DJ; Nichols, SD; Riker, RR; Smith, KE, 2021)	2.27
" Bioavailability data for healthy volunteers and patients with opioid use disorder, metastatic cancer, chronic pain from malignant or nonmalignant disease were available for analysis."	( Methadone bioavailability and dose conversion implications with intravenous and enteral administration: A scoping review. Craig, WY; Fraser, GL; Kemp, HD; Liu, J; McKelvy, DJ; Nichols, SD; Riker, RR; Smith, KE, 2021)	2.06
"Available evidence suggests the bioavailability of methadone is generally more than 75%, there is limited evidence for the currently recommended 1:2 ratio (intravenous:enteral), and a more appropriate dosing ratio may be 1:1."	( Methadone bioavailability and dose conversion implications with intravenous and enteral administration: A scoping review. Craig, WY; Fraser, GL; Kemp, HD; Liu, J; McKelvy, DJ; Nichols, SD; Riker, RR; Smith, KE, 2021)	2.32

Dosage Studied

The incidence of the side effects irritability and gastrointestinal troubles was significantly higher under OMT with levomethadone. The pronounced and variable fluctuations in methadone disposition evident in these patients highlight the need for an individualized approach to patient dosing and monitoring.

Excerpt	Relevance	Reference
" Dose-response curves for locomotor activity were also determined with morphine and methadone administered intraventricularly."	( Interactions between narcotic analgesics and benzodiazepine derivatives on behavior in the mouse. Davis, DC; Holtzman, SG; Shannon, HE, 1976)	0.48
" Evidence of tolerance was indicated by the fact that when the antinociceptive response to morphine was assessed by the hot-plate and the tail-flick procedures, a shift in the dose-response curve of morphine to the right occurred after an adequate single priming dose of morphine."	( Studies on tolerance development to single doses of morphine in mice. Huidobro, F; Huidobro-Toro, JP; Leong Way, E, 1976)	0.26
" Dinoracetylmethadol plasma levels remained relatively constant throughout the dosing interval."	( Disposition of acetylmethadol in relation to pharmacologic action. Inturrisi, CE; Kaiko, RF, 1975)	0.25
" It is concluded that sex hormones play an important role in the induction of epoxide hydratase and glutathione S-transferase by methadone, but not of aryl hydrocarbon hydroxylase, at this particular dosage regime."	( The effects of gonadectomy on the hepatic activities of aryl hydrocarbon hydroxylase, epoxide hydratase, and glutathione S-transferase in Wistar rats pretreated with oral methadone . HCl. Bellward, GD; Gontovnick, LS; Roelofs, L, 1979)	0.66
" Quantitatively, the dose-response relationship cannot be demonstrated though the spectrum of effect increased with higher doses as more spermatogenesis stages became more sensitive to the treatment."	( On the mutagenicity of methadone hydrochloride. Induced dominant lethal mutation and spermatocyte chromosomal aberrations in treated males. Badr, FM; Badr, RS; Rabouh, SA, 1979)	0.57
"Guinea pigs were injected SC for 3 weeks with 3 different dosage schedules of morphine or methadone, or with saline."	( Time course of dopaminergic hypersensitivity following chronic narcotic treatment. Almasi, J; Carlson, KR, 1979)	0.48
") dosing produced only a slight cross-tolerance to the rate-decreasing effects of anileridine and alphaprodine."	( Comparing the effects of anileridine, alphaprodine and fentanyl on schedule-controlled responding by pigeons. Leander, JD, 1978)	0.26
" Both dose-response and time-duration studies were conducted."	( Morphine and methadone-induced antinociception in rats permanently depleted of brain dopamine. Elchisak, MA; Harry, GJ; Rosecrans, JA, 1977)	0.63
"The results of a 2-year-study of the relationship between methadone dosage and treatment outcome are reported."	( Comparison of the effect of high and low doses of methadone on treatment outcome. Alston, DC; Angle, BP; Siassi, I, 1977)	0.75
" This study indicates that a pharmacokinetically optimized dosage regimen would be useful in increasing the therapeutic effectiveness of MMT."	( Methadone maintenance: plasma levels and therapeutic outcome. Anggård, E; Gunne, LM; Holmstrand, J, 1978)	1.7
" Cardiac output, heart rate, respiratory rate and minute volume were decreased below mean pre-drug control values after drug administration in the two higher dosage groups; cardiac output in both groups failed to return to pre-drug control levels."	( Effect of 1-alpha-acetylmethadol (LAAM) on various physiological parameters in the conscious dog. Catravas, JD; Davis, WM; Guinn, MM; Waters, IW, 1978)	0.26
"Neonatal mice were injected once daily with d,l-methadone in a dosage of 2 mg/kg."	( Inhibition by d,l-methadone of RNA and protein synthesis in neonatal mice: antagonism by naloxone or naltrexone. Hui, FW; Krikun, E; Smith, AA, 1978)	0.85
" When methadone was administered on a divided dosage regimen, there was a dramatic clinical improvement in both patients and a marked flattening of the curve of serum methadone levels."	( Serum methadone as an aid in managing methadone maintenance patients. Thornton, TL; Wahl, GF; Walton, RG, 1978)	1.22
" The opportunity to take medication home from the clinic on 4 days of the week was ranked as most desirable, on the average, followed by receiving cash payments ($30 and $10) and the opportunity for limited dosage self-control."	( Contingency management in a methadone maintenance program: availability of reinforcers. Bigelow, G; Stitzer, M, 1978)	0.55
" Two sources of external feedback, implicit dosage strength (liquid drug color) and explicit performance information (pursuit rotor feedback), were varied along with drug usage."	( Placebo attribution in methadone patients. Skarin, K; Sulzer, J, 1978)	0.57
" The starting dose was identical to the previously established dose of methadone, but beginning with the second visit, dosage was flexible."	( A cooperative clinical study of methadyl acetate. I. Three-times-a-week regimen. Gillis, RD; Klett, CJ; Ling, W, 1978)	0.49
" Dosage was fixed for the balance of the 40-week treatment period."	( Methadyl acetate and methadone as maintenance treatments for heroin addicts. A veterans administration cooperative study. Charuvastra, C; Kaim, SC; Klett, CJ; Ling, W, 1976)	0.57
" The initial dosage was 24 mg/day for methadone hydrochloride and 800 mg/day for propoxyphene napsylate."	( Heroin detoxification. A comparison of propoxyphene and methadone. Bleich, RN; Casas, SK; Russell, BA; Tennant, FS, 1975)	0.77
" It is suggested that reduction of methadone dosage in late pregnancy results in reduced incidence of withdrawal but must be carefully carried out."	( Observation and treatment of neonatal narcotic withdrawal. Chappel, JN; Davis, R; Gumpel, J; Madden, JD; Mejia, A; Zuspan, F, 1977)	0.53
"A direct and rapid high-performance liquid chromatographic assay for methadone hydrochloride in a flavored oral solution dosage form is described."	( High-performance liquid chromatographic analysis of methadone hydrochloride oral solution. Beasley, TH; Ziegler, HW, 1977)	0.74
" This observation was investigated in rabbits maintained on daily methadone 4 mg per kg of body weight after a period of 3 months on increasing dosage to assure drug tolerance."	( The stimulation of albumin sythesis by methadone. Kreek, MJ; Mongelli, JG; Oratz, M; Rothschild, MA; Schreiber, SS, 1976)	0.76
" Thus far, the most useful of several dosage forms studied is a suspension in an aluminum monostearate gel."	( Long-acting narcotic antagonist complexes. Gray, AP; Guardina, WJ, 1976)	0.26
"Methadone chlorhydrate has been administred to opiate addicts either for a short period with a decreasing dosage as a withdrawal cure, or for longterm treatments as a basis of a maintenance program."	( [A French experience with methadone]. Cuche, H; Deniker, P; Loo, H; Zarifian, E, 1975)	2
" No significant association was found between maternal dosage of methadone in the last trimester of pregnancy and lentth of gestation, birth weight, or the reported presence of withdrawal symptoms in the neonate."	( Results of 313 consecutive live births of infants delivered to patients in the New York City Methadone Maintenance Treatment Program. Bashkow, S; Calko, D; Newman, RG, 1975)	0.71
" Heroin addicts maintained on high dosage methadone (80-150 mg/day) also had depressed testosterone levels."	( Plasma testosterone levels in heroin addiction and during methadone maintenance. Mendelson, JE; Mendelson, JH; Patch, VD, 1975)	0.76
" Unit dose packaging is used because the oral solid dosage forms (including placebos) are made to look alike."	( Drug use and distribution in a pain rehabilitation center. Beckner, TF; Idsvoog, P, 1975)	0.25
"A colorimetric method for direct quantitative assay of methadone hydrochloride in liquid oral dosage forms is presented."	( Determination of methadone hydrochloride in a maintenance dosage formulation. Hoffmann, TJ; Thompson, RD, 1975)	0.84
" A mean quantity equal to 28% of the administered dose was excreted in the urine of a 48-h dosing interval as acetylmethadol and metabolites."	( Simultaneous determination of acetylmethadol and its active riotransformation products in human biofluids. Chatterjie, N; Inturrisi, CE; Kaiko, RF, 1975)	0.25
" Plasma testosterone levels decreased signifcantly when heroin dosage was between 45 and 65 mg/day contrasted to predrug base-line levels."	( Effects of heroin and methadone on plasma cortisol and testosterone. Ellingboe, J; McDougle, M; Mendelson, JH; Meyer, RE; Mirin, SM, 1975)	0.57
" Thus far, the most useful of several dosage forms studied is s suspension in an aluminum monostearate gel."	( Long-acting narcotic antagonist complexes. Gray, AP; Guardina, WJ, 1975)	0.25
" The maximum dosage permitted was 120 mg."	( Control of methadone dosage by patients. Goldstein, A; Hansteen, RW; Horns, WH, 1975)	0.64
" In the mothers, no significant differences were found with respect to dosage and duration of methadone treatment and years of heroin abuse."	( Cytogenetics of methadone-managed and heroin-addicted pregnant women and their newborn infants. Amarose, AP; Norusis, MJ, 1976)	0.82
" Methadone was administered according to four pre-established dosing schedules depending on the previous amount of daily consumed buprenorphine."	( Assessment and management of opioid withdrawal symptoms in buprenorphine-dependent subjects. Camí, J; Fernández, T; Ollé, JM; Peri, JM; San, L; Torrens, M, 1992)	1.19
" Available data from studies of beta-endorphin indicate that there is a [table; see text] normalization, rather than disruption, of the endogenous opioid system in general during steady state administration of methadone, as contrasted with intermittent dosing and then abrupt withdrawal of short-acting opiates such as heroin."	( Rationale for maintenance pharmacotherapy of opiate dependence. Kreek, MJ, 1992)	0.47
"Individual Dosing in Methadone Maintenance Therapy/Plasma level determination by means of high performance liquid chromatography versus immunoassay."	( [Individual dosing in methadone substitution therapy. Determination of concentration with high performance liquid chromatography in comparison to immunoassay]. Loimer, N; Rauch, B; Schmid, R, 1992)	0.92
"4 mg/ml for morphine and methadone, respectively, were achieved using an ascending dosage schedule."	( Morphine and methadone dependence in the rat: withdrawal and brain met-enkephalin levels. Olley, JE; Pierce, TL; Tiong, GK, 1992)	0.96
"min/ml and with dosing intervals less than 3 hours."	( Treatment of opioid-induced constipation with oral naloxone: a pilot study. Culpepper-Morgan, JA; Foley, K; Houde, RW; Inturrisi, CE; Kreek, MJ; Marsh, F; Portenoy, RK, 1992)	0.28
" Dosing was started at 360 mg of methadone per day and reduced over 12 days to an 80 mg/day maintenance dose."	( High-dose methadone and the need for drug measurements in plasma. Hay, A; Raistrick, D; Wolff, K, 1991)	0.96
" Three practical conclusions that can be drawn from this model are: (1) methadone dosage must be adequate (never less than 50-80 mg); (2) it should be more widely accepted that some patients may require lifelong methadone maintenance; and (3) longer-acting, better stabilizing methadone congeners, such as LAAM and its metabolites, should be brought into general use."	( Heroin addiction: neurobiology, pharmacology, and policy. Goldstein, A, )	0.36
" Counselor collaboration on medical issues, and dosing policies and practices are explored, as well as the clinical approach to tapering off methadone."	( Counseling issues in methadone maintenance treatment. Zweben, JE, )	0.65
" Significant predictors included professional classifications of the diagnosing and treatment-planning staff members, measures of early treatment services, client attitudes and satisfaction, methadone dosage level, and frequency of urine monitoring."	( Treatment predictors of tenure in methadone maintenance. Hubbard, RL; Joe, GW; Simpson, DD, 1991)	0.75
" Laboratory measurements of phenobarbital and methadone helped to identify the use of illicit methadone, as well as incorrect self-administration, such as the consumption of several days' dosage at one time."	( Measuring compliance in methadone maintenance patients: use of a pharmacologic indicator to "estimate" methadone plasma levels. Calvert, R; Feely, M; Hay, A; Raistrick, D; Wolff, K, 1991)	0.85
" Clinic dosage policies contribute significantly to retention in methadone maintenance treatment."	( Methadone dosage and retention of patients in maintenance treatment. Bell, J; Caplehorn, JR, 1991)	1.96
" drug abusers on levomethadon maintenance programs, adjustment of the levomethadon dosage may be necessary when specific therapy for HIV infection and associated diseases requires the use of drugs known to be potent inducers of the liver microsomal enzyme system."	( Pharmacokinetic interaction of antimicrobial agents with levomethadon in drug-addicted AIDS patients. Brockmeyer, NH; Goos, M; Mertins, L, 1991)	0.28
" The severity of abstinence symptoms correlated with maternal methadone dosage in both term and preterm infants."	( Neonatal opiate abstinence syndrome in term and preterm infants. Doberczak, TM; Kandall, SR; Wilets, I, 1991)	0.52
" It should also be emphasized that there is considerable variability among methadone programs in such vital areas as leadership, staffing patterns, organization, dosing procedures, location, physical plant, and availability of ancillary services."	( Psychotherapy and counseling for methadone-maintained opiate addicts: results of research studies. Luborsky, L; McLellan, AT; O'Brien, CP; Woody, GE, 1990)	0.79
" In the future, increasing the average dosage and the provision of injectable drug users will be discussed to assess their role in further harm reduction."	( The 'methadone by bus' project in Amsterdam. Buning, EC; Van Brussel, GH; Van Santen, G, 1990)	0.79
" CI was always preceded by a period of repetitive dosing of opioids."	( I.v. infusion of opioids for cancer pain: clinical review and guidelines for use. Foley, KM; Inturrisi, CE; Moulin, DE; Portenoy, RK; Rogers, A, 1986)	0.27
" On reduction of opioid dosage he had visual and auditory hallucinations and showed deterioration of consciousness progressing to coma."	( Unusual opioid withdrawal syndrome. A case-report. Grochow, LB; Hausheer, F; Kumor, KM, 1987)	0.27
" The study was done in three phases: a training phase in which training drugs were identified to subjects by letter code before the session, a test of acquisition phase in which the subject's ability to identify the training drug by letter code was tested and a generalization phase in which dose-response curves for the two active training drugs were tested."	( Three-choice drug discrimination in opioid-dependent humans: hydromorphone, naloxone and saline. Bickel, W; Bigelow, GE; Liebson, IA; Preston, KL, 1987)	0.27
" Physiologic measures and subject- and observer-rated behavioral responses were measured before dosing and for 2 hr after drug administration."	( Butorphanol-precipitated withdrawal in opioid-dependent human volunteers. Bigelow, GE; Liebson, IA; Preston, KL, 1988)	0.27
" Although the model is derived from a single subject, the simulations performed clearly suggest a need for altered methadone dosing in pregnancy."	( Altered methadone pharmacokinetics in pregnancy: implications for dosing. Camara, P; DePetrillo, P; Dudley, M; Griffiths, W; Swift, RM, 1989)	0.92
" Dosing intervals, pain intensity assessments and toxicity were evaluated."	( Does intravenous methadone provide longer lasting analgesia than intravenous morphine? A randomized, double-blind study. Enterline, J; Green, L; Grochow, L; Grossman, S; Sheidler, V, 1989)	0.62
" Dose-response curves were constructed for the opioid effects on C fibre evoked activity of dorsal horn nociceptive neurones following intrathecal application of each opioid, and the ED50 values were correlated with lipid solubility."	( Intrathecal opioids, potency and lipophilicity. Dickenson, AH; McQuay, HJ; Smallman, K; Sullivan, AF, 1989)	0.28
"5 to both morphine and methadone, and their dose-response curves were parallel."	( Differences in efficacies between morphine and methadone demonstrated in the guinea pig ileum: a possible explanation for previous observations on incomplete opioid cross-tolerance. Ivarsson, M; Neil, A, 1989)	0.84
" In very few patients the permanent success of the treatment was at high risk due to unsatisfactory social care, lack of social security measures, progression of the underlying disease, a too low methadone dosage level, and partnership conflicts."	( [Medical and psychosocial effects of methadone substitution in HIV infected substance-dependent patients]. Baumgart, P; Dorst, KG; Kupfer, U; von Eiff, M; Walger, P; Wilke, G, 1989)	0.74
" A semi-structured interview elicited the dosage of cyclizine used, its effects, the reasons for starting and persisting with abuse of cyclizine and the attitudes of the patients to it."	( Cyclizine abuse among a group of opiate dependents receiving methadone. McLean, PC; Melville, J; Ruben, SM, 1989)	0.52
" Administration of the drug should be on an individualized basis with conservative dosing in a well-monitored environment because somnolence and respiratory depression can occur."	( Continuous intravenous infusion of methadone for control of burn pain. Concilus, R; Denson, DD; Knarr, D; Raj, PP; Warden, G, )	0.41
"01) dipipanone and a dose-response relationship was evident."	( Effects of an opiate on cold-induced pain and the CNS in healthy volunteers. Crowley, D; Peck, AW; Phillipson, R; Posner, J; Telekes, A, 1985)	0.27
" In particular, studies of retention, counselor characteristics, program policies and goals, the nature and extent of services received by clients, the context in which treatment is administered, methadone dosage levels, and other such variables are reviewed."	( Drug abuse treatment process: a review of the literature. Allison, M; Hubbard, RL, 1985)	0.46
"Systemic administration of beta-funaltrexamine (beta-FNA) 24 hr before analgesic testing produced approximately a 10-fold parallel shift in the dose-response curves of the prototypic mu agonists morphine, I-methadone, fentanyl and etorphine in the mouse abdominal constriction test."	( Use of beta-funaltrexamine to determine mu opioid receptor involvement in the analgesic activity of various opioid ligands. Hynes, MD; Leander, JD; Reel, JK; Zimmerman, DM, 1987)	0.46
" Under this dosing schedule, the behavior-suppressing effects of buprenorphine returned to base-line levels within 4 days."	( Effects of buprenorphine, methadone and naloxone on acquisition of behavioral chains. Cleary, J; Ho, B; Nader, M; Thompson, T, 1988)	0.58
" Although buprenorphine dose was not associated with retention or illicit opioid use, patterns of withdrawal symptoms differed among dosage groups during the 30 day study."	( Buprenorphine detoxification from opioid dependence: a pilot study. Kleber, HD; Kosten, TR, 1988)	0.27
" However, the large variation in the half-life of methadone necessitated careful adjustment of the dosing interval in individual patients."	( A comparative study of the efficacy and pharmacokinetics of oral methadone and morphine in the treatment of severe pain in patients with cancer. Cherry, DA; Cousins, MJ; Gourlay, GK, 1986)	0.76
" Overall, the results show that a choice procedure can be used successfully to assess the reinforcing properties of drugs in methadone maintenance patients and that methadone dose increases can function as a reinforcer in this population even under blind dosing conditions."	( Choice of blind methadone dose increases by methadone maintenance patients. Bickel, WK; Higgins, ST; Stitzer, ML, 1986)	0.82
"Methadone dosage levels have typically been examined with regard to patient symptomatology, treatment retention, and continued narcotic use."	( Methadone dose levels and client characteristics in heroin addicts. Metzger, DS; Platt, JJ, 1987)	3.16
" In some cases a complete adherence to therapeutic program, allowing labour under very low methadone dosage (5 mg/day), minimized toxicological neonatal risk."	( Methadone in pregnancy: clinical-toxicological aspects. Chiarotti, M; De Giovanni, N; Falasconi, AM; Offidani, C, 1986)	1.93
"This paper summarizes data for 106 male opioid addicts which give evidence that there are demographic and clinical differences between groups of patients maintained in three ranges of methadone dosage (less than 35 mg, 36-59 mg, greater than 60 mg)."	( Methadone dosage: patient characteristics and clinical correlates. Calsyn, DA; Roszell, DK, 1986)	1.91
" The same dosage levels of BP and methadone were also given to pseudopregnant rats (PSP) with an induced decidual cell reaction (DCR) in an attempt to distinguish whether adverse effects occur in the maternal or fetal compartment or both."	( A comparative study of the reproductive effects of methadone and benzo[a]pyrene in the pregnant and pseudopregnant rat. Bui, QQ; Tran, MB; West, WL, 1986)	0.8
" Three times per week dosing of LAAM proved to be a safe and effective treatment agent for the majority of subjects."	( Clinical experiences with 959 opioid-dependent patients treated with levo-alpha-acetylmethadol (LAAM). Pumphrey, E; Rawson, RA; Seecof, R; Tennant, FS, 1986)	0.27
" These data suggest that maternal drug abuse and increased methadone dosage during pregnancy may predispose infants to the development of strabismus."	( Occurrence of strabismus in infants born to drug-dependent women. Calhoun, JH; Ehrlich, S; Finnegan, LP; Matteucci, T; Nelson, LB, 1987)	0.52
" A pharmacokinetic-pharmacodynamic model may be useful for the individualization of analgesic dosage and therefore the optimization of pain management in patients with chronic pain."	( Pharmacokinetics and pharmacodynamics of methadone in patients with chronic pain. Colburn, WA; Foley, KM; Houde, RW; Inturrisi, CE; Kaiko, RF, 1987)	0.54
"Selected methodological issues of appropriate control procedures and dose-response relationships are discussed with respect to the issue of interpretation."	( Issues of methodology and interpretation in clinical and animal behavioral teratology studies. Hutchings, DE, )	0.13
" Drug intervention should be on a regular schedule--avoid prn dosage of pain medications."	( Dilemmas in managing prostate carcinoma (Part II): Metastatic disease. Ahmann, FR, 1985)	0.27
" The dosing of various drugs currently in use is also discussed."	( The neonatal narcotic abstinence syndrome: a brief review. Calabrese, JR; Gulledge, AD, 1985)	0.27
"Monkeys receiving acetylmethadol thrice weekly were more active on dosing days, and less active on between-dose days, than while drug-free."	( Variability in simian motor and social behavior with alternating-day acetylmethadol. Crowley, TJ; Macdonald, MJ; Zerbe, G, 1985)	0.27
"53) between pupillary constriction 120 minutes after drug dosing and the average dollar value of subjects' reported heroin use per week."	( Pupillary response to methadone challenge in heroin users. Bigelow, GE; Higgins, ST; Liebson, IA; McCaul, ME; Stitzer, ML, 1985)	0.58
" Rats were dosed continuously with morphine hydrochloride by giving a daily dose through tubes connected to small, subcutaneously implanted reservoirs."	( An implanted reservoir of morphine solution for rapid induction of physical dependence in rats. Goode, PG, 1971)	0.25
" In contrast, removal of the morphine pellet 3 hours prior to the analgesic evaluation apparently unmasked the expression of tolerance and cross-tolerance as evidenced by a three fold, parallel shift to the right of the analgesic dose-response curve for subcutaneously administered etorphine and methadone and a seven fold shift to intracerebroventricularly administered morphine."	( Differential analgesic cross-tolerance to morphine between lipophilic and hydrophilic narcotic agonists. Paktor, J; Vaught, JL, 1984)	0.44
" Adverse reactions occurred more often with higher doses of morphine and codeine; the dose-response relationship could not be evaluated for the other three drugs."	( Clinical effects of parenteral narcotics in hospitalized medical patients. Miller, RR, 1980)	0.26
" As expected, the dosage intervals increased gradually over the first few days of treatment, the daily dose decreasing from 30-80 mg on the first day to 10-40 mg at the end of the week."	( Patient-controlled dose regimen of methadone for chronic cancer pain. Anggård, E; Ginman, C; Hansen, J; Hartvig, P; Jakobsson, PA; Nilsson, MI; Rane, A; Säwe, J, 1981)	0.54
" Patients randomly assigned to the gradual group (group G) began 4-mg/wk reduction the Monday of week 9 and reached zero dosage (placebo) the Monday of week 23; patients in the abrupt group (group A) continued to receive 50, 50, and 65 mg until the Monday of week 23, when their dosage was dropped to zero (placebo)."	( Methadyl acetate (LAAM) in the treatment of heroin addicts. II. Double-blind comparison of gradual and abrupt detoxification. Goldstein, A; Inturrisi, CE; Judson, BA, 1983)	0.27
" Disulfiram was administered at a dosage of 125 mg/day for seven days and 250 mg/day thereafter for 36 weeks."	( Use of disulfiram for alcoholics in methadone maintenance programs. A Veterans Administration Cooperative Study. Charuvastra, VC; Ling, W; O'Brien, CP; Weiss, DG, 1983)	0.54
" Pupil diameter and subjective responses were measured 15 min before dosing and 15, 30, 45, 60, 90, and 120 min after dosing."	( Diazepam and methadone interactions in methadone maintenance. Bigelow, GE; Griffiths, RR; Liebson, IA; Preston, KL; Stitzer, ML, 1984)	0.64
" Dosage for both groups was reduced to 0 mg during weeks 11-13."	( Chronic opiate use during methadone detoxification: effects of a dose increase treatment. Bigelow, GE; Liebson, IA; McCaul, ME; Stitzer, ML, 1984)	0.57
" The rectal dosage forms included aqueous solutions and fatty suppositories."	( Preliminary study on the absorption profile after rectal and oral administration of methadone in human volunteers. Fiets, G; Meijer, DK; Moolenaar, F; Visser, J, 1984)	0.49
" No toxic side effects of clonidine were observed at the dosage level used."	( Clonidine treatment of neonatal narcotic abstinence syndrome. Caruso, KA; Cohen, DJ; Ehrenkranz, RA; Hoder, EL; Kleber, HD; Leckman, JF; Poulsen, J, 1984)	0.27
"Innovative treatment techniques such as self-regulation of methadone dosage and client knowledge of dosage are not widely accepted by small community methadone maintenance programs."	( Methadone maintenance in the small community drug abuse clinic. Hebert, SW; Lauterbach, EC, 1983)	1.95
"5% of tests) rates of opiate-positive urine test results during two weeks of dosage stabilization."	( Treatment outcome in methadone detoxification: relationship to initial levels of illicit opiate use. Bigelow, GE; Liebson, I; McCaul, ME; Stitzer, ML, 1983)	0.58
" During one dosage interval a pulse dose of M-d3 was administered intravenously instead of the oral M-dose (M-d0)."	( Pharmacokinetics of methadone in methadone maintenance treatment: characterization of therapeutic failures. Anggård, E; Grönbladh, L; Nilsson, MI; Widerlöv, E, 1983)	0.59
" These LAAM-induced changes demonstrated dose- and time-dependence within that dosage range producing mortality."	( L-alpha-acetylmethadol-induced tissue alterations in mice. Freeman, RW; Harbison, RD; James, RC, 1984)	0.27
" Moreover, PEA excretion bore no relation to methadone dosage among 24 steady-dosed subjects."	( Depression during methadone withdrawal: no role for beta-phenylethylamine. Chuang, LW; Karoum, F; Kaufmann, CA; Kreek, MJ, 1984)	0.86
" Because the two maintenance programs differed in clinical practices and in enforcement of rules, it was concluded that clients who continue chronic heroin use need not only long-term dosage increases, but also clear, consistently applied program policies."	( Chronic heroin use during methadone treatment: a test of the efficacy of high maintenance doses. Havassy, BE; Tschann, JM, 1984)	0.57
" Dosage regimens of clonidine must be individualized according to symptoms and side effects and closely supervised because of varying sensitivity to clonidine's sedative, hypotensive, and withdrawal-suppressing effects."	( Clonidine in opiate withdrawal: review and appraisal of clinical findings. Resnick, RB; Washton, AM, )	0.13
" Dosage as low as 5 mg caused significant increase in saccade undershoot especially to target displacements greater than 10-15 degrees."	( Specific oculomotor deficit after acute methadone. I. Saccadic eye movements. Gross, K; Rothenberg, S; Schottenfeld, S; Selkoe, D, 1980)	0.53
"Four groups of Charles River CD-1 pregnant mouse dams were dosed subcutaneously daily with 5, 10, 20, and 28 mg/kg of methadone during day 6 to 15 of gestation."	( Developmental toxic effect after subcutaneous injections of methadone in Charles River CD-1 mice. Bui, QQ; Sperling, F; West, WL, 1983)	0.72
" Rapid and continuous pain relief without serious side-effects was achieved by "ad libitum" dosage in the first 3-5 days."	( Clinical evaluation of oral methadone in treatment of cancer pain. Anggård, E; Ginman, C; Hansen, J; Hartvig, P; Jakobsson, PA; Nilsson, MI; Rane, A; Säwe, J, 1982)	0.56
" In treatment of severe cancer pain such adaptive changes in methadone pharmacodynamics and pharmacokinetics are best managed by a regimen involving a fixed dose but a flexible and patient-controlled dosage interval."	( Clinical pharmacokinetics of methadone. Anggård, E; Meresaar, U; Nilsson, MI, 1982)	0.8
" Outcome measures included retention to the end of the dosing schedule, use of illicit drugs during treatment, subjective discomfort, satisfaction, staff ratings of global progress, and durability of change at a three-month follow-up."	( Withdrawal from heroin in three or six weeks. Comparison of methadyl acetate and methadone. Hargreaves, WA; Sorensen, JL; Weinberg, JA, 1982)	0.49
" These studies showed that short-term effects of oral methadone can be readily detected during a 24-hr dosing regimen."	( Short-term effects of oral methadone in methadone maintenance subjects. Bigelow, GE; Liebson, I; McCaul, ME; Stitzer, ML, 1982)	0.81
" Drug accumulation occurred in some subjects, but within the study range, dosage was not related to maximum plasma levels nor to accumulation."	( Plasma and urine disposition of 1-alpha-acetylmethadol and its principal metabolites in man. Chinn, DM; Finkle, BS; Holmes, ED; Jennison, TA; Ling, W, )	0.13
" A pulse dose of M-d3 was given on Days 1 and 25 of two dosage regimens, one with a continuous 30 mg dose (n = 6), and the other with 30 mg for 10 days, followed by 60 mg as the maintenance dose (n = 6)."	( Pharmacokinetics of methadone during maintenance treatment: adaptive changes during the induction phase. Anggård, E; Gunne, LM; Holmstrand, J; Nilsson, MI, 1982)	0.59
" Under controlled inpatient conditions established to assess dosage guidelines and to examine specific signs and symptoms of withdrawal, ten (91%) of 11 patients were able to withdraw completely from methadone therapy by the end of a six-day period."	( Clonidine and naltrexone. A safe, effective, and rapid treatment of abrupt withdrawal from methadone therapy. Braverman, P; Charney, DS; Heninger, GR; Kleber, HD; Murburg, M; Redmond, DE; Riordan, CE; Sternberg, DE, 1982)	0.67
"The changes in effects on motor activity of rats upon repeated (48 day) dosing with four narcotic analgesics were determined."	( Motility response of rats to chronic constant-dose treatment with narcotics. Davis, WM; Hemnani, KL; Pace, HB, 1982)	0.26
"Study was made of the relationship between methadone dosage policy and retention in drug abuse treatment."	( Methadone maintenance dosage levels and program retention. Brown, BS; Iglehart, AS; Watters, JK, )	1.84
" It is hypothesized that tolerance to methadone resembles immunity comparable to that against infections, and not a dose-response curve."	( Methadone dose assessment in heroin addiction. Aylett, P, 1982)	1.98
"05); (c) under conditions of maximal electrical stimulation of the vagus, pancreatic response was unsignificantly increased; (d) dose-response curves to secretin and CCK-PZ were unsignificantly changed."	( [Responses of exocrine pancreas to a six month oral treatment by methadone in rats (author's transl)]. Chariot, J; Lehy, T; Potet, F; Rozé, C; Souchard, M; Vaille, C, )	0.37
" Methadone dosing adjustments should be anticipated when phenytoin is initiated or discontinued in methadone-maintained patients."	( Phenytoin-induced methadone withdrawal. Benowitz, NL; Jaffery, NF; Kreek, MJ; Pond, SM; Tong, TG, 1981)	1.51
" The data suggest that the maintenance dosage of methadone need not be changed in stable chronic liver disease."	( Methadone disposition in patients with chronic liver disease. Fanizza, AM; Gelb, AM; Kreek, MJ; Novick, DM; Stenger, RJ; Yancovitz, SR, 1981)	1.96
" The following trends were found: (1) clients' dosage of methadone reduced over time, (2) clients' progressed toward drug-free life-style changes over time, and (3) the intensification of counseling was associated with a reduction of the frequency of chemical abuse of clients."	( Effects of intensive counseling on client outcome in a methadone maintenance program. Kuncel, EE, 1981)	0.76
" The marked individual variation in methadone pharmacodynamics and kinetics, and the possibilities both of cellular and metabolic tolerance, require an individually optimized dosage regimen."	( Single dose pharmacokinetics and bioavailability of methadone in man studied with a stable isotope method. Anggård, E; Holmstrand, J; Meresaar, U; Nilsson, MI, 1981)	0.79
" Under controlled inpatient conditions established to assess dosage guidelines and to examine specific signs and symptoms of withdrawal, 20 of 25 (80%) patients were able to withdraw completely from methadone by the end of a two-week period."	( The clinical use of clonidine in abrupt withdrawal from methadone. Effects on blood pressure and specific signs and symptoms. Charney, DS; Heninger, GR; Kleber, HD; Redmond, DE; Sternberg, DE, 1981)	0.7
"Methadone maintenance patients who use benzodiazepine drugs were interviewed about the dosage levels, patterns, frequency and motives for their use of these drugs."	( Diazepam use among methadone maintenance patients: patterns and dosages. Grabowski, J; Griffiths, RR; Hawthorne, JW; McLellan, AT; Stitzer, ML, 1981)	2.03
" They also preferred LAAM to methadone on nine of 15 criteria such as the dosage schedule, feeling 'normal', and reduction of craving for heroin."	( A comparison of thrice weekly LAAM and daily methadone in employed heroin addicts. Czertko, G; Freedman, RR, 1981)	0.81
" It was found that following the administration of the daily dosage of methadone, A-State was significantly reduced but no changes in A-Trait occurred."	( State-trait anxiety in methadone maintenance patients. Teichman, M, 1981)	0.81
" Patients were assigned to three dosage groups."	( Extraneous drug use in methadone-supported patients. Chapman, C; Hartfield, M; Seow, SS; Swensen, G; Willis, D, 1980)	0.57
" It was found that methadone dosage was not positively correlated with psychopathology, but that diffuse nonspecific psychopathology was observed in all participants."	( Methadone Patients: dosage, psychopathology, and research participation. Katz, SE; Meltzer, JD, 1980)	2.03
") produced a significant rightward shift of the dose-response curve of morphine, levorphanol, methadone, pilocarpine, clonidine and tizanidine; a modest, but not statistically significant, rightward shift of the dose-response curves of the mu-selective peptides DAMGO ([D-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin) and PL017 ([N-Me-Phe3,D-Pro4]-morphiceptin); and no shift of the dose-response curves of alfentanil, carfentanil, fentanyl, sufentanil, or beta-endorphin."	( The 'glibenclamide-shift' of centrally-acting antinociceptive agents in mice. Martinez, RP; Raffa, RB, 1995)	0.51
" The results indicate that there is a substantial treatment dose-response relationship."	( Treatment intensity and reduction in drug use for cocaine-dependent methadone patients: a dose-response relationship. Foote, J; Handelsman, L; Lovejoy, M; Magura, S; Palij, M; Rosenblum, A; Stimmel, B, )	0.37
" To determine if raising the daily methadone dosage is an effective way to eliminate cocaine abuse, 74 methadone maintenance patients maintained at daily dosages between 30 and 80 mg and who chronically abused cocaine were studied by a standard protocol."	( Cocaine abuse in methadone maintenance patients is associated with low serum methadone concentrations. Shannon, J; Tennant, F, 1995)	0.91
" The median daily methadone dosage was 60 mg."	( Methadone maintenance treatment and the nonstress test. Levine, AB; Rebarber, A, )	1.91
"The aim of this study was to assess the influence of maternal methadone dosage on the severity of neonatal withdrawal."	( Maternal methadone dosage and neonatal withdrawal. Darlow, BA; Horwood, LJ; Lennox, R; Malpas, TJ, 1995)	0.95
" Dosing was double-blind and double-dummy."	( Buprenorphine versus methadone in the treatment of opioid-dependent cocaine users. Bigelow, GE; Liebson, IA; Stitzer, ML; Strain, EC, 1994)	0.61
" Moreover, dosing every 6 hr for 5 days induced an increase in the catabolism of methadone itself."	( The effect of methadone on the immune status of B6C3F1 mice. Brown, RD; Butterworth, LF; Fuchs, BA; Harris, LS; LeVier, DG; McCay, JA; Munson, AE; Musgrove, DL; White, KL, 1995)	0.88
"A retrospective, inception cohort, nonrandomized control design was employed to evaluate the effects of daily vs twice daily dosing of methadone on opiate/cocaine use, and noncompliance with urine toxicology requests in methadone-maintained pregnant women, n = 45."	( Methadone dosing and pregnancy: impact on program compliance. DePetrillo, PB; Rice, JM, 1995)	1.94
" Cocaine users were more likely than nonusers of cocaine to use heroin at all methadone dosage levels."	( Heroin use during methadone maintenance treatment: the importance of methadone dose and cocaine use. Davenny, K; Friedland, GH; Hartel, DM; Klein, RS; Kline, J; Schoenbaum, EE; Selwyn, PA, 1995)	0.85
"2 mg/kg of body weight dosage by intramuscular (IM) administration."	( Pharmacokinetic properties of methadone hydrochloride after single intramuscular administration in adult dairy goats. Brooks, DL; Kock, M; Thompson, E; Vulliet, PR, 1994)	0.58
"Two doses of methadone were administered by osmotic minipump from Day 8 of gestation through parturition, a dosing technique previously shown to produce physical dependence in the dams."	( Prenatal administration of methadone in the rat: acoustic startle amplitude and the rest-activity cycle at 30 days of age. Brake, SC; Hamowy, AS; Hutchings, DE; Liu, PY; Zmitrovich, AC, )	0.8
" A good dose-response relationship was found between the 100% suppressive withdrawal sign doses of DHE and the degree of withdrawal sign in heroin addicts."	( [Clinical assessment of physical dependence potential of dihydroetorphine hydrochloride (DHE)]. Cai, ZJ; Ge, Y; Li, M; Sun, WL, 1994)	0.29
" Dosing was double-blind and double-dummy."	( Comparison of buprenorphine and methadone in the treatment of opioid dependence. Bigelow, GE; Liebson, IA; Stitzer, ML; Strain, EC, 1994)	0.57
" In both groups, 56% of patients remained in treatment through the 16-week flexible dosing period."	( Comparison of buprenorphine and methadone in the treatment of opioid dependence. Bigelow, GE; Liebson, IA; Stitzer, ML; Strain, EC, 1994)	0.57
"The results of this study provide further support for the utility of buprenorphine as a new medication in the treatment of opioid dependence and demonstrate efficacy equivalent to that of methadone when used during a clinically guided flexible dosing procedure."	( Comparison of buprenorphine and methadone in the treatment of opioid dependence. Bigelow, GE; Liebson, IA; Stitzer, ML; Strain, EC, 1994)	0.76
" It is concluded that the reduction of HIV transmission could be enhanced by improvements in methadone programs, particularly ensuring adequate dosing and high retention rates."	( Injecting behaviour and risky needle use amongst methadone maintenance clients. Ali, RL; Cormack, S; Dyer, KR; Gaughwin, MD; White, JM, 1994)	0.76
" Relapse rates were related to dosage level, client monitoring with urinalyses, and methadone take-home privileges in some clinics, and hence, these time-varying treatment events were important factors in treatment outcomes."	( Treatment process and relapse to opioid use during methadone maintenance. Joe, GW; Sells, SB; Simpson, DD, 1994)	0.76
" Treatment retention was high for both dosage conditions."	( Low (40 mg) versus high (80 mg) dose methadone in a 180-day heroin detoxification program. Banys, P; Delucchi, KL; Reilly, PM; Sees, KL; Tusel, DJ, )	0.4
"Consensus on the optimal dosing of methadone in the treatment of opioid dependence has not yet been achieved, with some programs committed to low dose regimens."	( Methadone dose and treatment outcome. Bigelow, GE; Liebson, IA; Stitzer, ML; Strain, EC, 1993)	2.01
" Logistic regression indicated that alcoholism among MMTP patients was associated with years drinking, years of sharing needles, utilization of drug abuse detoxification but not alcohol detoxification, smaller increases in methadone dosage over time, and psychiatric symptomatology."	( Correlates of alcohol use among methadone patients. el-Bassel, N; Schilling, RF; Su, KH; Turnbull, JE, 1993)	0.75
"Two doses of methadone were administered by osmotic minipump from Day 8 of gestation through parturition, a dosing technique previously shown to produce physical dependence in the dams."	( Prenatal administration of methadone in the rat increases offspring acoustic startle amplitude at age 3 weeks. Brake, SC; Church, SH; Hutchings, DE; Malowany, D; Zmitrovich, AC, )	0.8
" To prevent such mistakes in the future a change in labelling of the bottle giving directions for correct dosing is suggested."	( [Iatrogenic methadone poisoning]. Rabl, W; Sigrist, T; Sutter, K, 1993)	0.66
"kg-1) confirms that daily dosing at steady-state is adequate to maintain effective plasma concentrations throughout the dosing interval."	( Steady-state pharmacokinetics of methadone in opioid addicts. Calvert, R; Hay, AW; Raistrick, D; Wolff, K, 1993)	0.57
" This suggests that the acute effects of methadone on smoking are nullified as clients habituate to dose level, and that decisions regarding appropriate methadone dosage can be made on other grounds."	( Cigarette smoking and methadone dose levels. Campbell, BK; Stark, MJ, 1993)	0.87
"This spectrum of relationships supports the concept that careful reduction of the maternal methadone dosage during pregnancy under intensive medical and psychosocial surveillance may benefit the drug-exposed new-born infant clinically."	( Relationship between maternal methadone dosage, maternal-neonatal methadone levels, and neonatal withdrawal. Doberczak, TM; Friedmann, P; Kandall, SR, 1993)	0.8
"To compare the dose effectiveness of low to moderate doses of methadone in a sample of a contemporary population of opioid abusers, because the optimal dosing of methadone in the treatment of opioid dependence remains an issue."	( Dose-response effects of methadone in the treatment of opioid dependence. Bigelow, GE; Liebson, IA; Stitzer, ML; Strain, EC, 1993)	0.83
"All participants were initially treated with active methadone for a minimum of 5 weeks and then received 15 weeks of stable dosing at 50, 20, or 0 mg per day."	( Dose-response effects of methadone in the treatment of opioid dependence. Bigelow, GE; Liebson, IA; Stitzer, ML; Strain, EC, 1993)	0.84
"There is a dose-response effect for methadone treatment."	( Dose-response effects of methadone in the treatment of opioid dependence. Bigelow, GE; Liebson, IA; Stitzer, ML; Strain, EC, 1993)	0.86
" As hypothesized, 6 mg of buprenorphine were superior to 2 mg of buprenorphine in reducing illicit opioid use, but higher dosage did not improve treatment retention."	( Buprenorphine versus methadone maintenance for opioid dependence. Falcioni, J; Kosten, TR; Schottenfeld, R; Ziedonis, D, 1993)	0.6
" Methadone dosing was not contingent upon ingestion of antituberculous medication(s)."	( Successful adherence to observed prophylaxis and treatment of tuberculosis among drug users in a methadone program. Gourevitch, MN; Panero, MS; Selwyn, PA; Wasserman, W, 1996)	1.42
" Testing consisted of three daily sessions of fixed cocaine dosing (four injections; 0, 16 and 48 mg/70 kg) and three daily sessions of cocaine self-administration with a choice procedure (16, 32 and 48 mg/70 kg vs."	( Effects of methadone or buprenorphine maintenance on the subjective and reinforcing effects of intravenous cocaine in humans. Fischman, MW; Foltin, RW, 1996)	0.68
" However, cocaine exposed infants did not require more medication for withdrawal management either in terms of dosage or of days treated."	( Neonatal withdrawal syndrome in infants exposed to cocaine and methadone. Carroll, KM; Mayes, LC, 1996)	0.53
"The aims of this study were to describe the analgesia, side effects, and dosage and the causes of suspension of treatment in a large sample of advanced cancer patients with pain after treatment with oral methadone from 7 to 90 days."	( Clinical experience with oral methadone administration in the treatment of pain in 196 advanced cancer patients. Brunelli, C; De Conno, F; Groff, L; Ripamonti, C; Ventafridda, V; Zecca, E, 1996)	0.77
"A regimen of self-administered oral methadone at fixed doses and flexible patient-controlled dosage intervals to achieve adequate analgesia, while avoiding toxic effects of methadone accumulation, was used in 24 patients requiring opioid therapy."	( Patient-controlled analgesia with oral methadone in cancer pain: preliminary report. Caligara, M; Mercadante, S; Sapio, M; Serretta, R, 1996)	0.84
" Male long-Evans rats were shaved prior to dosing to obtain their drug-free hair."	( Quantitative analysis of methadone and two major metabolites in hair by positive chemical ionization ion trap mass spectrometry. Foltz, RL; Gygi, SP; Nagasawa, PR; Rollins, DE; Wilkins, DG, 1996)	0.6
" The reactivity of the nonstress tests, biophysical profile scores and time needed to complete the biophysical profiled before and after methadone dosing were compared."	( Effect of methadone on the biophysical profile. Cejtin, HE; Mills, A; Swift, EL, 1996)	0.9
" In a follow-up period of nine weeks after replacement of l-methadone with racemic methadone, there was also no significant increase in complaints about withdrawal symptoms, although six patients needed an elevation of their daily dosage by at least 20 mg racemic methadone."	( The efficacy of L-methadone and racemic methadone in substitution treatment for opiate addicts--a double-blind comparison. Finkbeiner, T; Gastpar, M; Leifert, K; Scherbaum, N, 1996)	0.87
" Three scoring systems to quantify dose-response relationships for withdrawal are described: (1) using the mean number of withdrawal behaviors per animal within each treatment group; (2) using the sum of the percentage of animals within a treatment group displaying each of the withdrawal behaviors; and (3) a modification of these, to further isolate the naloxone-induced component of the withdrawal score, that is, subtraction of data obtained from saline-challenged animals from those of naloxone-challenged rats."	( The induction and quantitation of methadone dependence in the rat. Hope, W; Pierce, TL; Raper, C, 1996)	0.57
" Selection of optimal methadone dosage is a complex problem in which the favorable neurobehavioral outcome associated with increased growth and gestational age must be weighed against the risks associated with more severe neonatal withdrawal."	( Neonatal outcome following methadone exposure in utero. Ager, JW; Cepeda, EE; Hagopian, GS; Sokol, RJ; Wardell, JN; Wolfe, HM, )	0.74
" After achieving adequate analgesia with regular dosing of oral methadone (T1), patient-controlled analgesia with methadone was administered for 3 days (T2)."	( Opioid-sparing effect of diclofenac in cancer pain. Barresi, L; Caligara, M; Dardanoni, G; Mercadante, S; Sapio, M; Serretta, R, 1997)	0.54
" Methadone dosing was flexible, with patient participation in dose decisions."	( The relationship of methadone dose and other variables to outcomes of methadone maintenance. Maddux, JF; Prihoda, TJ; Vogtsberger, KN, 1997)	1.53
" Cumulative dose-response analysis in the tail-flick test revealed an ED50 value for intrathecal (spinal) l-methadone of 15."	( d-Methadone is antinociceptive in the rat formalin test. Elliott, KJ; Inturrisi, CE; Shimoyama, M; Shimoyama, N, 1997)	1.23
"There is some evidence that monitoring methadone plasma concentration may be of benefit in dosage adjustment during methadone maintenance therapy for heroin (opiate) dependence."	( The pharmacokinetics of methadone in healthy subjects and opiate users. Calvert, R; Feely, M; Hay, AW; Raistrick, D; Rostami-Hodjegan, A; Shires, S; Tucker, GT; Wolff, K, 1997)	0.87
" Our analysis also suggested that parameters describing plasma concentrations of methadone after a single oral dose in healthy subjects may not be used for predicting and adjusting dosage in opiate users receiving methadone maintenance therapy unless coupled with feedback concentration monitoring techniques (for example Bayesian forecasting)."	( The pharmacokinetics of methadone in healthy subjects and opiate users. Calvert, R; Feely, M; Hay, AW; Raistrick, D; Rostami-Hodjegan, A; Shires, S; Tucker, GT; Wolff, K, 1997)	0.83
" The formulation prepared from tablets provides flexible dosing in patients undergoing rapid withdrawal from methadone."	( Formulation and stability of naltrexone oral liquid for rapid withdrawal from methadone. Fawcett, JP; Morgan, NC; Woods, DJ, 1997)	0.74
"Although methadone maintenance remains the best available treatment for opioid addiction, the need for daily oral dosing limits the effectiveness of methadone as opioid substitution therapy."	( Hydromorphone polymer implant. A potential alternative to methadone maintenance. Grossman, SA; Rhodes, DJ, )	0.79
" Persistent weight retardation at 12 months was correlated with methadone dosage during pregnancy, but not the need for phenobarbitone therapy."	( Infants born to narcotic dependent mothers: physical growth patterns in the first 12 months of life. Chant, DC; Gray, PH; Hayes, AJ; Tudehope, DI; Vance, JC, 1997)	0.54
"To evaluate the Methadone Dispensing Circuit in Amsterdam by identifying determinants of methadone dosage and client characteristics in the different types of methadone programmes."	( Differentiation in the Amsterdam methadone dispensing circuit: determinants of methadone dosage and site of methadone prescription. Coutinho, RA; Langendam, MW; Reurs, H; van Ameijden, EJ; van Brussel, GH; van den Hoek, AA; van Haastrecht, HJ, 1998)	0.93
"From 1985 to 1994, methadone dosage increased from 41 to 59 mg/day."	( Differentiation in the Amsterdam methadone dispensing circuit: determinants of methadone dosage and site of methadone prescription. Coutinho, RA; Langendam, MW; Reurs, H; van Ameijden, EJ; van Brussel, GH; van den Hoek, AA; van Haastrecht, HJ, 1998)	0.91
" Topics in program organization are described: indications, daily dosage and its administration, treatment duration, professional job-sharing and control of the treatment."	( [Use of methadone in the treatment of narcotic addiction]. Tiljak, H, 1998)	0.73
" A free dosing schedule was used with no upper limit for methadone dosing but with a maximum buprenorphine dose of 8 mg."	( Comparison of buprenorphine and methadone maintenance in opiate addicts. Eder, H; Fischer, G; Gombas, W; Jagsch, R; Kasper, S; Stühlinger, G, 1998)	0.83
" In general, the GPs offer a more flexible approach regarding frequency of consultations, urine tests and dosing regimen while the AC approach is more structured."	( Differences between general practitioner- and addiction centre-prescribed buprenorphine substitution therapy in France. Preliminary results. Brunelle, E; Vignau, J, 1998)	0.3
" Dosage is important for effectiveness as are counseling, rehabilitation services, and employment support."	( Effectiveness of methadone maintenance for heroin addiction. Murray, JB, 1998)	0.64
" Symptoms are easily recognised; pharmacological treatment can consist of either sedatives or replacement drugs whose dosage depends on the severity of withdrawal symptoms evaluated using a score system."	( Neonatal drug addiction. Fabris, C; Perathoner, C; Prandi, G; Soldi, A, 1998)	0.3
" For patients in maintenance, methadone dosage and clinic policy were the most important factors for retention."	( Retention in treatment of heroin users in Italy: the role of treatment type and of methadone maintenance dosage. Bargagli, AM; D'Ippoliti, D; Davoli, M; Pasqualini, F; Perucci, CA, 1998)	0.81
" At the time of the study, the majority of the test persons (29) were on low dosage methadone maintenance (up to 60 mg/day)."	( [Driving fitness/driving capacity of patients treated with methadone]. Bär, W; Friedrich-Koch, A; Hauri-Bionda, R, 1998)	0.77
" Seven patients in the methadone group maintained the same initial dosage until death, whereas only one patient in the morphine group did not require opioid dose escalation."	( Morphine versus methadone in the pain treatment of advanced-cancer patients followed up at home. Agnello, A; Barresi, L; Calderone, L; Casuccio, A; Mercadante, S; Serretta, R, 1998)	0.96
" Contrary to the expectation that methadone patients who consumed excessive amounts of alcohol would require higher dosages of methadone, it was found that nonalcohol-abusing methadone patients requested the higher dosage levels."	( Methadone patients and alcohol abuse. Ottomanelli, G, 1999)	2.03
" In addition, the most current and efficacious dosage regimen for the rectal administration of acetaminophen (40."	( Blocks and other techniques pediatric surgeons can employ to reduce postoperative pain in pediatric patients. Broadman, LM, 1999)	0.3
" However, despite recommendations regarding effective dosing of methadone, controlled clinical trials of higher-dose methadone have not been conducted."	( Moderate- vs high-dose methadone in the treatment of opioid dependence: a randomized trial. Bigelow, GE; Liebson, IA; Stitzer, ML; Strain, EC, 1999)	0.85
" Comparisons of physiological and subjective measures collected in agonist exposure sessions indicate that LAAM is not less potent than methadone under acute dosing conditions."	( Relative potency of levo-alpha-acetylmethadol and methadone in humans under acute dosing conditions. Bigelow, GE; Buchhalter, AR; Eissenberg, T; Stitzer, ML; Walsh, SL, 1999)	0.76
"Although methadone is widely used to treat opiate dependence, guidelines for its dosage are poorly defined."	( Population pharmacokinetics of methadone in opiate users: characterization of time-dependent changes. Calvert, R; Hay, AW; Raistrick, D; Rostami-Hodjegan, A; Tucker, GT; Wolff, K, 1999)	1.01
" By accounting for adaptive kinetic changes, the POP-PK model provides an improved basis for forecasting plasma methadone concentrations to predict and adjust dosage of the drug and to monitor compliance in opiate-users on maintenance treatment."	( Population pharmacokinetics of methadone in opiate users: characterization of time-dependent changes. Calvert, R; Hay, AW; Raistrick, D; Rostami-Hodjegan, A; Tucker, GT; Wolff, K, 1999)	0.8
"Higher peak dose of tincture of opiate solution (TOS) and longer dosing interval were found to be related to longer length of hospital stay."	( Shorter dosing interval of opiate solution shortens hospital stay for methadone babies. Jones, HC, 1999)	0.54
"Lower peak doses of TOS and shorter dosing intervals may be associated with shorter hospital stays for infants with neonatal abstinence syndrome secondary to maternal methadone treatment."	( Shorter dosing interval of opiate solution shortens hospital stay for methadone babies. Jones, HC, 1999)	0.73
" Intra- and inter-patient variations in methadone bioavailability have been observed after oral methadone treatment and this makes it difficult to predict a dosing regimen."	( The roles of P-glycoprotein and intracellular metabolism in the intestinal absorption of methadone: in vitro studies using the rat everted intestinal sac. Barthe, L; Bouër, R; Houin, G; Philibert, C; Tournaire, C; Woodley, J, 1999)	0.79
" Issues to be explored include a potential role in treating patients who have poorly responsive pain syndromes, such as neuropathic pain, or who develop a rapid tolerance to other opioids; the possibility of extending dosing intervals to every 12 or 24 hours; and its possible use as a first-line opioid."	( Role of methadone in the management of pain in cancer patients. Bruera, E; Neumann, CM, 1999)	0.74
" However, an individual increase of the methadone dosage and measures to achieve high treatment retention could contribute to the prevention of HIV among drug users."	( Methadone maintenance treatment modalities in relation to incidence of HIV: results of the Amsterdam cohort study. Coutinho, RA; Langendam, MW; van Ameijden, EJ; van Brussel, GH, 1999)	2.01
"A double-blind, cross-over design was used to compare the effects of a 33% increase in patient's daily dosage of methadone with a matched placebo linctus."	( Additional methadone increases craving for heroin: a double-blind, placebo-controlled study of chronic opiate users receiving methadone substitution treatment. Bolton, J; Curran, HV; Smyth, C; Wanigaratne, S, 1999)	0.9
"In patients unable to maintain an effective methadone blood level throughout the dosing interval, fluvoxamine can help increase the methadone blood level and alleviate opiate withdrawal symptoms."	( A therapeutic use of the methadone fluvoxamine drug interaction. DeMaria, PA; Serota, RD, 1999)	0.87
"Traditionally, methadone maintenance therapy has been a once-daily dosing schedule."	( Alterations in methadone metabolism during late pregnancy. Jarvis, MA; Kniseley, JS; Schnoll, SH; Wu-Pong, S, 1999)	1.01
" Therefore methadone should be titrated carefully and increases in dosage should be performed every third or fourth day."	( [Methadone as an analgesic]. Clausen, T; Eriksen, J; Kamp-Jensen, M, 2000)	1.61
" Thirty males and 21 females participated in treatment planning, goal setting, and determining methadone dosage level."	( Effects of control and motivation on treatment outcome. Kludt, CJ; Perlmuter, L, )	0.35
" Buyers in treatment appear to be motivated by a desire to supplement their own prescriptions because they are dissatisfied with the particular drug prescribed, dosage and formulation."	( Diversion of prescribed drugs by drug users in treatment: analysis of the UK market and new data from London. Farrell, M; Fountain, J; Gossop, M; Griffiths, P; Strang, J, 2000)	0.31
" Methadone dosage and frequency of methadone programme attendance in themselves were not significantly related to cessation of injecting."	( Methadone maintenance and cessation of injecting drug use: results from the Amsterdam Cohort Study. Coutinho, RA; Langendam, MW; van Ameijden, EJ; van Brussel, GH, 2000)	2.66
"Steadily increasing the methadone dosage in a harm reduction setting may be useful in supporting injecting drug users in the process of cessation of injecting and reducing the spread of HIV-infection."	( Methadone maintenance and cessation of injecting drug use: results from the Amsterdam Cohort Study. Coutinho, RA; Langendam, MW; van Ameijden, EJ; van Brussel, GH, 2000)	2.06
" Most of the biomedical and epidemiological research literature on methadone obscures these power dynamics by technocratically debating dosage titrations in a social vacuum."	( Disciplining addictions: the bio-politics of methadone and heroin in the United States. Bourgois, P, 2000)	0.8
" The assay was applied to plasma protein and erythrocyte binding studies and a 96-h pharmacokinetic study in two healthy female volunteers following oral dosing with rac-methadone."	( Development and application of a chiral high performance liquid chromatography assay for pharmacokinetic studies of methadone. Boulton, DW; Devane, CL, 2000)	0.71
" Serum methadone levels (SMLs) may guide practitioners dosing decisions, especially for those patients who have low SMLs despite higher methadone doses."	( When "enough" is not enough: new perspectives on optimal methadone maintenance dose. Eap, CB; Leavitt, SB; Maxwell, S; Paris, P; Shinderman, M, )	0.83
"Since many methadone maintenance treatment (MMT) clinics in the United States do not share with patients, information concerning their methadone dosage, we aimed to investigate the impact of patients being informed of their methadone dosage and the influence of ending blind dosing on treatment outcome."	( A naturalistic study on ending blind dosing in a methadone maintenance clinic in Israel. Adelson, M; Bleich, A; Gelkopf, M; Hayward, R, 2001)	0.95
"This study compared the safety and efficacy of sublingual buprenorphine tablets with oral methadone in a population of opioid-dependent individuals in a double-blind, randomized, 6-week trial using a flexible dosing procedure."	( Double-blind randomized trial of buprenorphine and methadone in opiate dependence. Déglon, JJ; Ladewig, D; Livoti, S; Petitjean, S; Stohler, R; Uehlinger, C; Waldvogel, D, 2001)	0.78
"There is evidence that plasma methadone measurements may be of benefit in dosage adjustment during methadone maintenance treatment for opiate dependence."	( Population-based pharmacokinetic approach for methadone monitoring of opiate addicts: potential clinical utility. Hay, AW; Raistrick, D; Rostami-Hodjegan, A; Tucker, G; Wolff, K, 2000)	0.85
" Random samples during treatment could be used to assess methadone dosing by comparing predicted with observed measurements for each individual."	( Population-based pharmacokinetic approach for methadone monitoring of opiate addicts: potential clinical utility. Hay, AW; Raistrick, D; Rostami-Hodjegan, A; Tucker, G; Wolff, K, 2000)	0.81
" For this reason, methadone is often viewed as a second line opioid, after other opioids with a more predictable dose-response have been tried."	( Methadone analgesia in cancer pain patients on chronic methadone maintenance therapy. Cheville, AL; Gonzales, GR; Kornick, C; Manfredi, PL; Payne, R, 2001)	2.09
"Methadone, a synthetic opioid, has unique pharmacodynamics and pharmacokinetics, which contribute to its unique ability to relieve pain unresponsive to other potent opiates and its unique dosing and drug interactions."	( Methadone for relief of cancer pain: a review of pharmacokinetics, pharmacodynamics, drug interactions and protocols of administration. Davis, MP; Walsh, D, 2001)	3.2
"Methadone maintenance is the premier pharmacological treatment for opioid addiction, but it is rarely informed by evidence-based practice guidelines for dosage monitoring and adjustment."	( Therapeutic drug monitoring in methadone maintenance: choosing a matrix. Epstein, D; Moolchan, ET; Umbricht, A, 2001)	2.04
" Addjusting the methadone dosage may be necessary when ritonavir is used."	( Ritonavir (Norvir) and methadone. , 1998)	0.96
"Several sessions at the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) described interactions, toxicities, and dosing options of new anti-HIV drugs."	( New anti-HIV drug interactions, toxicities, and dosing options. Bartnof, HS, 1999)	0.3
" When initiating treatment, controlled-release preparations of opioids are generally favoured, and are combined with immediate release morphine to prevent or treat 'breakthrough' pain and to enable the optimum opioid dosage to be calculated."	( [Treatment of pain in cancer with systemically administered opioids]. de Wit, R; Enting, RH; Lieverse, PJ; Smitt, PA; van der Rijt, CC; Wilms, EB, 2001)	0.31
" Buprenorphene may be one alternative to methadone, however the optimum dosage pattern is as yet unknown."	( [Review of scientific evidence on alternatives to methadone in the psychopharmacologic treatment of opiate dependence]. Aizpuru, A; Aizpurua, I; Iruín, A; Ruiz de Apodaka, J; Zapiraín, E, )	0.65
"A six-month interval (baseline) during which methadone doses above 99 mg required individual approval by the clinic's physician was compared with the subsequent 16-month period in which a policy of patient-regulated methadone dosing with no preset upper limit was implemented."	( Implementation of a clinic policy of client-regulated methadone dosing. Gilmore-Thomas, KK; McMillan, DE; Miller, FB; Robles, E, 2001)	0.82
" Although the current analysis did not rule out differences in pharmacological effects as a contributing factor, the results are consistent with an interpretation of a dose-response association between psychosocial/psychotherapeutic support and detoxification outcome."	( Predictors for completing an inpatient detoxification program among intravenous heroin users, methadone substituted and codeine substituted patients. Backmund, M; Eichenlaub, D; Meyer, K; Schütz, CG, 2001)	0.53
" Two maintenance treatments are available: methadone is only delivered in specialized centres while high dosage (HD) buprenorphine can be prescribed by all general practitioners and in specialized centres."	( Comparison of methadone and high dosage buprenorphine users in French care centres. Barrau, K; Bellemin, B; Chuniaud-Louche, C; Micallef, J; San Marco, JL; Thirion, X, 2001)	0.93
" They also suggest that the behaviours of maintenance treatment users depend less on the nature of the maintenance drug (methadone or high dosage buprenorphine), than the nature of the delivery and monitoring practices."	( Comparison of methadone and high dosage buprenorphine users in French care centres. Barrau, K; Bellemin, B; Chuniaud-Louche, C; Micallef, J; San Marco, JL; Thirion, X, 2001)	0.88
"To measure the interdose milk to plasma ratio (M/P) of R- and S-methadone during multiple dosing in lactating mothers taking medium to high doses of methadone (> 40 mg daily), and to assess likely infant exposure."	( Distribution of R- and S-methadone into human milk during multiple, medium to high oral dosing. Begg, EJ; Hackett, LP; Ilett, KF; Malpas, TJ, 2001)	0.85
"Breastfeeding during medium to high dose methadone appears to be 'safe' according to conventional criteria because the dosage is < 10%."	( Distribution of R- and S-methadone into human milk during multiple, medium to high oral dosing. Begg, EJ; Hackett, LP; Ilett, KF; Malpas, TJ, 2001)	0.88
" Development of opioid abstinence syndrome was evaluated during fentanyl and methadone dosage reductions and for 72 hours thereafter."	( Enteral methadone to expedite fentanyl discontinuation and prevent opioid abstinence syndrome in the PICU. Cash, J; Lugo, RA; MacLaren, R; Pribble, CG; Vernon, DD, 2001)	0.97
" In some patients with cancer the long half-life of methadone offers the advantage of extended dosing intervals to 12 and even 24 hours, further research is also needed in this area."	( Methadone use in cancer patients with pain: a review. Bruera, E; Sweeney, C, 2002)	2.01
" Therapeutic drug monitoring for methadone in plasma continues to be evaluated for use in establishing adequate dosing and detecting diversion, and new methods have been devised for measurement of the optical isomers of methadone in plasma."	( Toxicologic aspects of heroin substitution treatment. Cone, EJ; Preston, KL, 2002)	0.6
" Thus, in agreement with the negative results from acute dosing studies in primates and humans, chronic ketoconazole treatment does not appear to reduce cocaine or opioid use in humans maintained on methadone."	( Ketoconazole increases cocaine and opioid use in methadone maintained patients. Feingold, A; Gonsai, K; Kosten, TR; Oliveto, A; Sevarino, KA, 2002)	0.76
" These recommendations address: antepartum issues including treatment, dosage and pharmacological considerations, medical conditions and lab tests, intrapartum issues, postpartum concerns including breastfeeding, neonatal withdrawal, and developmental effects associated with methadone."	( Clinical management of methadone dependence during pregnancy. Curet, LB; Dorato, V; Wallerstedt, C; Wilbourne, P, 2001)	0.8
"LAAM and methadone are both full mu opiate agonists and have been shown to reduce dependence on heroin when given continuously under supervised dosing conditions."	( LAAM maintenance vs methadone maintenance for heroin dependence. Clark, N; Dunlop, A; Gijsbers, A; Ling, W; Lintzeris, N; Ritter, A; Whelan, G, 2002)	1.06
" After 6-8 weeks on LAAM, plasma concentrations of the norLAAM metabolite varied significantly by LAAM dosing day, plasma adrenocorticotropin (ACTH) concentrations were significantly increased compared to methadone, and two of the seven subjects remaining in LAAM treatment were free of illicit opioids and nonprescribed methadone."	( The use of levo-alpha-acetylmethadol (LAAM) in methadone patients who have not achieved heroin abstinence. Appel, P; Borg, L; Ho, A; Joseph, H; Kreek, MJ; Moody, D; Wells, A, 2002)	0.76
"Fifty eligible MM patients with active HCV and concomitant liver fibrosis were treated with interferon/ribavirin combination therapy using standard dosing regimens."	( Treating hepatitis C in methadone maintenance patients: an interim analysis. Sylvestre, DL, 2002)	0.62
" The modest increase in Amsterdam is explained by low background risk of overdose mortality, low starting dosage and the low threshold to treatment."	( An increase in overdose mortality during the first 2 weeks after entering or re-entering methadone treatment in Amsterdam. Buster, MC; van Brussel, GH; van den Brink, W, 2002)	0.54
"The percentage of patients receiving methadone dosage levels less than the recommended 60 mg/d has decreased from 79."	( Changes in methadone treatment practices: results from a national panel study, 1988-2000. D'Aunno, T; Pollack, HA, 2002)	0.98
" BZD abusers (BAs) were found more often to be polydrug abusers, their methadone dosage was higher than non-abusers (NBAs), they started to abuse drugs in general and heroin in particular earlier than NBA, and they had higher self-rated psychopathology and psychological distress scores."	( Benzodiazepine abuse in a methadone maintenance treatment clinic in Israel: characteristics and a pharmacotherapeutic approach. Adelson, M; Bleich, A; Gelkopf, M; Weizman, T, 2002)	0.85
" These two viewpoints are presented in the light of a number of specific methadone maintenance treatment and drug abuse related issues such as the question whether drug abuse is an illness of the body, the mind or society; whether the disease model really de-stigmatized drug abuse; what the correct methadone dosing policy should be; the place of psychotherapy in methadone maintenance treatment and drug abuse and how polydrug abuse should be treated."	( An integration of three approaches to addiction and methadone maintenance treatment: the self-medication hypothesis, the disease model and social criticism. Bleich, A; Gelkopf, M; Levitt, S, 2002)	0.8
" Individuals exposed to opioid treatment for pain management during surgical procedures or maintained on oral methadone for treatment of drug addiction show either no effect or a suppressed immune system, depending on dosage and, in the case of methadone-maintained patients, duration of drug treatment."	( Opioids, immunology, and host defenses of intravenous drug abusers. Alonzo, NC; Bayer, BM, 2002)	0.53
" Dose-response functions for heroin, methadone, LAAM, three other isomers of acetylmethadol: alpha- d-acetylmethadol, beta- d-acetylmethadol, beta- l-acetylmethadol, and its precursor, beta- l-methadol were examined."	( Heroin discriminative stimulus effects of methadone, LAAM and other isomers of acetylmethadol in rats. Beardsley, PM; May, EL; Newman, JL; Vann, RE, 2002)	0.85
" Because of the high morbidity and mortality associated with opioid dependence, it is of major importance that methadone is used at an effective dosage in maintenance treatment: at least 60 mg/day, but typically 80-100 mg/day."	( Interindividual variability of the clinical pharmacokinetics of methadone: implications for the treatment of opioid dependence. Baumann, P; Buclin, T; Eap, CB, 2002)	0.76
" Appropriate daily dosing to achieve these levels is usually between 50 and 150 mg methadone, with the occasional need for even higher doses in the third trimester."	( Methadone trough levels in pregnancy. Berghella, V; Drozdick, J; Hill, M; Kaltenbach, K, 2002)	1.98
"To determine whether maternal methadone dosage affects duration and degree of neonatal narcotic withdrawal."	( Relationship between maternal methadone dosage and neonatal withdrawal. Dashe, JS; Jackson, GL; Olscher, DA; Sheffield, JS; Todd, SJ; Wendel, GD, 2002)	0.89
" We evaluated indices of neonatal withdrawal according to the maximum daily methadone dosage in the last week of pregnancy."	( Relationship between maternal methadone dosage and neonatal withdrawal. Dashe, JS; Jackson, GL; Olscher, DA; Sheffield, JS; Todd, SJ; Wendel, GD, 2002)	0.83
" Median methadone dosage was 20 mg (range 0-150 mg), and 32 infants (46%) were treated for narcotic withdrawal."	( Relationship between maternal methadone dosage and neonatal withdrawal. Dashe, JS; Jackson, GL; Olscher, DA; Sheffield, JS; Todd, SJ; Wendel, GD, 2002)	1.04
"Maternal methadone dosage was associated with duration of neonatal hospitalization, neonatal abstinence score, and treatment for withdrawal."	( Relationship between maternal methadone dosage and neonatal withdrawal. Dashe, JS; Jackson, GL; Olscher, DA; Sheffield, JS; Todd, SJ; Wendel, GD, 2002)	1.02
" The dosage of the two comparatine groups is given according to Documentation, the method of abserving the treatment protocols and detoxification standard is according to current regulation."	( [Clinial study of "qingjunyin" detoxification for the treatment of heroin addicts]. Lan, S; Lu, H; Wang, G; Yuan, D; Zhan, C, 1997)	0.3
"Severity of opioid dependence, and performance on two successive runs of the Wisconsin Card Sorting Test (WCST), were assessed in 39 right-handed male and female methadone patients who had been randomly assigned to either a recently dosed (n=21) or 24 hr abstinent (n=18) condition."	( Neuropsychological correlates of opioid dependence and withdrawal. Lyvers, M; Yakimoff, M, 2003)	0.52
"To assess the efficacy of buprenorphine compared with methadone maintenance therapy for opioid dependence in a large sample using a flexible dosing regime and the marketed buprenorphine tablet."	( Buprenorphine versus methadone maintenance therapy: a randomized double-blind trial with 405 opioid-dependent patients. Ali, R; Danz, C; Mattick, RP; O'Brien, S; White, JM; Wolk, S, 2003)	0.89
"Patients received buprenorphine or methadone as indicated clinically using a flexible dosage regime."	( Buprenorphine versus methadone maintenance therapy: a randomized double-blind trial with 405 opioid-dependent patients. Ali, R; Danz, C; Mattick, RP; O'Brien, S; White, JM; Wolk, S, 2003)	0.91
"037), but not separately for the single-day or alternate-day dosing phases."	( Buprenorphine versus methadone maintenance therapy: a randomized double-blind trial with 405 opioid-dependent patients. Ali, R; Danz, C; Mattick, RP; O'Brien, S; White, JM; Wolk, S, 2003)	0.64
" NV as well as MM displayed a dose-response effect in plasma ACTH and cortisol levels."	( Corticotropin-releasing factor testing reveals a dose-dependent difference in methadone maintained vs control subjects. Bart, G; Green, M; Ho, A; Kreek, MJ; Schluger, JH, 2003)	0.55
" Studies began one hour before methadone dosing to avoid the expected increase in prolactin that coincides with peak plasma levels of methadone."	( Suppressed prolactin response to dynorphin A1-13 in methadone-maintained versus control subjects. Bart, G; Borg, L; Green, M; Ho, A; Kreek, MJ; Schluger, JH, 2003)	0.86
" Additional data collected included optimum dosing and dosage schedules, adverse reactions and common side-effects, and other information intended to clarify buprenorphine's benefit-risk relationship and to help prepare guidelines for its safe marketing and utilization by physicians in general clinical practice."	( Clinical efficacy of buprenorphine: comparisons to methadone and placebo. Ling, W; Wesson, DR, 2003)	0.57
" The 164 subjects included 41 patients in 1-mg, 41 patients in 3-mg, and 41 patients in 8-mg dosage group of buprenorphine, and also 41 patients in the 30-mg dosage group of methadone."	( Methadone versus buprenorphine maintenance for the treatment of heroin-dependent outpatients. Ahmadi, J, 2003)	1.96
" Fifty-one patients were inducted onto buprenorphine using the same dosing protocol with the first dose of 4 mg buprenorphine."	( Cessation of methadone maintenance treatment using buprenorphine: transfer from methadone to buprenorphine and subsequent buprenorphine reductions. Bell, J; Breen, CL; Harris, SJ; Hawken, L; Lenné, M; Lintzeris, N; Mattick, RP; Mendoza, E; Ritter, AJ, 2003)	0.69
"There were no significant difference between the transfer at 30 mg and transfer when 'uncomfortable' dosing protocols in severity of withdrawal on transfer from methadone to buprenorphine."	( Cessation of methadone maintenance treatment using buprenorphine: transfer from methadone to buprenorphine and subsequent buprenorphine reductions. Bell, J; Breen, CL; Harris, SJ; Hawken, L; Lenné, M; Lintzeris, N; Mattick, RP; Mendoza, E; Ritter, AJ, 2003)	0.88
" Axis I and II psychiatric diagnosis was assessed and methadone dosage and history of abuse was recorded."	( Treatment of benzodiazepine dependence in methadone maintenance treatment patients: a comparison of two therapeutic modalities and the role of psychiatric comorbidity. Adelson, M; Bleich, A; Gelkopf, M; Melamed, Y; Weizman, T, 2003)	0.83
" The major areas which were addressed by this report are Initial assessment of candidates for MMT Appropriate settings for initiation of MMT (general and special cases) Appropriateness of methadone supportive therapy Co-treatments and accompanying measures Dosage schedules and pharmacokinetic testing Withdrawal from MMT Miscellaneous questions Appropriateness of other (non-methadone) substitution treatment Summary statements for each of the above categories are derived from the panel meeting and presented in the report."	( Appropriateness of methadone maintenance treatment for opiate addiction: evaluation by an expert panel. Besson, J; Burnand, B; Eastus, C; Eggenberger, C; Hämmig, R; Vader, JP, 2003)	0.84
"This study examines the pharmacokinetic/pharmacodynamic interactions between (1) lopinavir-ritonavir (L/R), a fixed combination of protease inhibitors used for the treatment of HIV disease, and (2) ritonavir alone at the same dosage as that in the L/R formulation, with methadone, an opiate frequently used in substance abuse pharmacotherapy for opioid (heroin)-dependent injection drug users, many of whom are infected with HIV."	( The protease inhibitor lopinavir-ritonavir may produce opiate withdrawal in methadone-maintained patients. Friedland, G; Jatlow, P; McCance-Katz, EF; Rainey, PM, 2003)	0.73
" Even if MMT at high dosage is recommended as therapy for reducing illicit opioid use and promoting longer retention in treatment, at present day "the organisation and regulation of the methadone maintenance treatment varies widely"."	( Methadone maintenance at different dosages for opioid dependence. Faggiano, F; Lemma, P; Versino, E; Vigna-Taglianti, F, 2003)	1.95
" Both dose-response and temporal associations of noncontingent voucher receipt with drug-positive urines were assessed."	( Do noncontingent vouchers increase drug use? Epstein, DH; Gupman, AE; Preston, KL; Schroeder, JR; Umbricht, A, 2003)	0.32
" The trial utilised a flexible dosing regime that was tailored to the clinical need of the patients, with high maximum doses, using the marketed formulation, under double-blind conditions."	( Buprenorphine versus methadone maintenance: a cost-effectiveness analysis. Ali, R; Bell, J; Doran, CM; Mattick, RP; Shanahan, M; White, J, 2003)	0.64
" Methadone daily dosage was also analyzed during this study."	( Methadone and the hospice patient: prescribing trends in the home-care setting. Alt, CJ; Gallagher, R; Knowlton, CH; McMath, JA; Weschules, DJ, 2003)	2.67
"The purpose of this study was to determine whether maternal methadone dosage correlates with neonatal withdrawal in a large heroin-addicted pregnant population."	( Maternal methadone dose and neonatal withdrawal. Berghella, V; Chennat, J; Cherpes, J; Hill, MK; Kaltenbach, K; Lim, PJ, 2003)	0.98
" After in-hospital stabilization, women were given daily methadone therapy under direct surveillance, with liberal dosage increases according to maternal withdrawal symptoms."	( Maternal methadone dose and neonatal withdrawal. Berghella, V; Chennat, J; Cherpes, J; Hill, MK; Kaltenbach, K; Lim, PJ, 2003)	0.98
" For all cutoffs that were used for high versus low dose and for both the average and last methadone dosage analyses, neonatal withdrawal was similar."	( Maternal methadone dose and neonatal withdrawal. Berghella, V; Chennat, J; Cherpes, J; Hill, MK; Kaltenbach, K; Lim, PJ, 2003)	0.96
"The maternal methadone dosage does not correlate with neonatal withdrawal; therefore, maternal benefits of effective methadone dosing are not offset by neonatal harm."	( Maternal methadone dose and neonatal withdrawal. Berghella, V; Chennat, J; Cherpes, J; Hill, MK; Kaltenbach, K; Lim, PJ, 2003)	1.11
"Opioid effects were of a similar overall magnitude following dosing for each drug and showed an inverse association with plasma drug concentrations, which peaked later for morphine compared to (R)-methadone (6."	( Comparative pharmacodynamics and pharmacokinetics of methadone and slow-release oral morphine for maintenance treatment of opioid dependence. Bochner, F; Mitchell, TB; Somogyi, AA; White, JM, 2003)	0.76
" Methadone and LAAM dosing was supervised through local community pharmacies."	( A randomized trial comparing levo-alpha acetylmethadol with methadone maintenance for patients in primary care settings in Australia. Bammer, G; Clark, N; Kutin, JJ; Lintzeris, N; Panjari, M; Ritter, AJ, 2003)	1.47
" There were two dosing errors."	( A randomized trial comparing levo-alpha acetylmethadol with methadone maintenance for patients in primary care settings in Australia. Bammer, G; Clark, N; Kutin, JJ; Lintzeris, N; Panjari, M; Ritter, AJ, 2003)	0.56
" With time the dosing often increases because of tolerance."	( Methadone dosage for prevention of opioid withdrawal in children. Cimino, M; Fletcher, JE; Heard, AM; Heard, CM; Kielma, D; Siddappa, R, 2003)	1.76
"Consumed amount of narcotics per day and the course of dosage of injectable heroin in different treatment regimes."	( Dosage regimes in the prescription of heroin and other narcotics to chronic opioid addicts in Switzerland--Swiss national cohort study. Blättler, R; Bürki, C; Christen, S; Gschwend, P; Gutzwiller, F; Rehm, J; Seidenberg, A; Steffen, T, 2004)	0.32
" The mean daily dosage was 474 mg for intravenous application and 993 mg for the smokeable form."	( Dosage regimes in the prescription of heroin and other narcotics to chronic opioid addicts in Switzerland--Swiss national cohort study. Blättler, R; Bürki, C; Christen, S; Gschwend, P; Gutzwiller, F; Rehm, J; Seidenberg, A; Steffen, T, 2004)	0.32
"The sample mean methadone dose was 111 mg, with a lower dosage level in Oslo than in the other counties."	( [Methadone dose, treatment duration and heroin use in drug-assisted rehabilitation]. Kornør, H; Waal, H, 2004)	1.58
"In an international perspective, this sample has a generally high dosage level, long treatment duration and good treatment outcomes."	( [Methadone dose, treatment duration and heroin use in drug-assisted rehabilitation]. Kornør, H; Waal, H, 2004)	1.23
" For R-methadone (active isomer), C(max), AUC(0-24 h), and C(min) were unchanged, but percent unbound 4 hours after dosing was reduced by 12%."	( The effects of once-daily saquinavir/minidose ritonavir on the pharmacokinetics of methadone. Berenson, CS; Buggé, CJ; Cloen, D; de Caprariis, PJ; DiFrancesco, R; Esch, A; Espinosa, O; Hewitt, RG; Ljungqvist, A; Palic, B; Schur, JL; Shelton, MJ, 2004)	1
" Effects of retention status misclassification on time in the program were assessed with a Cox model for clients who received continuous daily dosing or short carries."	( Client retention in the British Columbia Methadone Program, 1996-1999. Anderson, JF; Warren, LD, )	0.4
" Adequate daily dosing appears crucial to both initial retention and return to treatment."	( Client retention in the British Columbia Methadone Program, 1996-1999. Anderson, JF; Warren, LD, )	0.4
" Pupil diameters and/or plasma concentrations of methadone and the primary metabolite EDDP were measured after 10 mg intravenous or oral methadone HCl, dosed 1 h after oral quinidine (600 mg) or placebo."	( The effect of quinidine, used as a probe for the involvement of P-glycoprotein, on the intestinal absorption and pharmacodynamics of methadone. Hoffer, C; Kharasch, ED; Whittington, D, 2004)	0.78
" Fixed interval dosing schedules conducted over several days are associated with a high risk of serious morbidity and mortality."	( Methadone for cancer pain. Nicholson, AB, 2004)	1.77
" Most reported that they determine dosing levels on an individual patient basis."	( Physicians practicing in methadone treatment programs: who are they and what do they do? Crum, L; Diesenhaus, H; Dunlap, L; Flannery, B; Kasten, JJ; Murdoch, O; Roussel, AE; Suerken, C; Wechsberg, WM, 2004)	0.63
" MTD excretion was higher in men, decreased with increased urinary pH, and increased with daily dosage of MTD; these factors explain 32% of the total variance of urinary MTD."	( Compliance with methadone-based substitutive treatment: a proposed model based on immunoassay urinary sample screening. Bézie, Y; Billaud, E; Boutouyrie, P; Illier, C; Lillo, A; Prognon, P; Talon, V, 2004)	0.67
" Daily supervised dosing by a pharmacist for the first six months resulted in significantly better treatment retention (80% vs 46%) and lower heroin use."	( French field experience with buprenorphine. Auriacombe, M; Daulouède, JP; Dubernet, J; Fatséas, M; Tignol, J, 2004)	0.32
" Effectiveness of Methadone maintenance program affects methadone dosage policy, treatment duration and ancillary services."	( [Economic efficiency of methadone maintenance and factors affecting it]. Padaiga, Z; Subata, E; Vanagas, G, 2004)	0.96
"Rectal administration of methadone may be an alternative to intravenous and oral dosing in cancer pain, but the bioavailability of the rectal route is not known."	( Bioavailabilities of rectal and oral methadone in healthy subjects. Dale, O; Kharasch, ED; Sheffels, P, 2004)	0.9
" Bioequivalence testing was conducted of total, R-, and S-methadone area under the serum or plasma concentration-time curve during the 24-hour dosing interval at steady state (AUCss) and maximum concentration in serum or plasma (Cmax)."	( Effect of tenofovir disoproxil fumarate on the pharmacokinetics and pharmacodynamics of total, R-, and S-methadone. Berenson, CS; Booker, BM; Bullock, JM; Cloen, D; Coakley, DF; Flaherty, JF; Haas, CE; Kearney, BP; Liaw, S; Smith, PF; Yale, K, 2004)	0.78
" However, the pharmacology underpinning the effects of methadone is little studied despite controversies about dosing in relation to outcome."	( Using [11C]diprenorphine to image opioid receptor occupancy by methadone in opioid addiction: clinical and preclinical studies. Ahmad, R; Brooks, DJ; Daglish, MR; Hume, SP; Lingford-Hughes, A; Malizia, AL; Melichar, JK; Myles, JS; Nutt, DJ; Taylor, LG; Williams, TM, 2005)	0.82
" In comparison to (R)-methadone, plasma nor- and dinor-LAAM concentrations fluctuated little over the dosing interval."	( Evaluation of levo-alpha-acetylmethdol (LAAM) as an alternative treatment for methadone maintenance patients who regularly experience withdrawal: a pharmacokinetic and pharmacodynamic analysis. Bochner, F; Newcombe, DA; Somogyi, AA; White, JM, 2004)	0.87
" The active R-methadone enantiomer area under the plasma concentration-time curve during a dosing interval (AUCt-ss, Cmax-ss, and the minimum plasma concentration at steady state (Cmin-ss) were decreased by 13%, 25%, and 21%, respectively, after coadministration of methadone and amprenavir."	( Pharmacokinetics and pharmacodynamics of methadone enantiomers after coadministration with amprenavir in opioid-dependent subjects. Bigelow, GE; Christopher, J; Fuchs, EJ; Hendrix, CW; Lou, Y; Martinez, E; Snidow, JW; Wakeford, J; Wire, MB, 2004)	0.95
"No a priori adjustment in methadone dosage is required during coadministration with amprenavir as there is only a small effect on R-methadone exposure and no evidence of opioid withdrawal."	( Pharmacokinetics and pharmacodynamics of methadone enantiomers after coadministration with amprenavir in opioid-dependent subjects. Bigelow, GE; Christopher, J; Fuchs, EJ; Hendrix, CW; Lou, Y; Martinez, E; Snidow, JW; Wakeford, J; Wire, MB, 2004)	0.89
" Withdrawal scores at the time of dosing were higher in the TOP patients (9."	( Comparison of tincture of opium and methadone to control opioid withdrawal in a Thai treatment centre. Ali, R; Bochner, F; Foster, DJ; Jittiwutikarn, J; Somogyi, AA; White, JM, 2004)	0.6
" Regular pain assessments combined with appropriate analgesic administration at regular dosing intervals, adjunctive drug therapy for control of adverse effects and associated symptoms, and nonpharmacological interventions are recommended."	( Cancer pain management in children. Mercadante, S, 2004)	0.32
" The patients' maintenance methadone dosage and urine tests for drug abuse during the month before and of the survey were recorded."	( Significantly higher methadone dose for methadone maintenance treatment (MMT) patients with chronic pain. Adelson, M; Gordon, J; Peles, E; Schreiber, S, 2005)	0.94
"3mg; number of days/month dosed in the clinic was 13."	( Deaths of clients in methadone treatment in Texas: 1994-2002. Maxwell, JC; Pullum, TW; Tannert, K, 2005)	0.65
" It may be an appropriate replacement for opioids when side effects have limited further dosage escalation."	( Methadone treatment for pain states. Kral, LA; Toombs, JD, 2005)	1.77
" It may be necessary to increase the dosage of methadone during interferon treatment."	( Methadone and buprenorphine maintenance therapies for patients with hepatitis C virus infected after intravenous drug use. Buntinx, F; Matheï, C; Robaeys, G; Verrando, R, )	1.83
"Desired adjustment of methadone dose, perceived participation in dosage regulation, and satisfaction with methadone treatment centres were assessed in a sample of opioid-dependent patients from the Valencia Region (eastern Spain)."	( Patient perspectives on methadone maintenance treatment in the Valencia Region: dose adjustment, participation in dosage regulation, and satisfaction with treatment. Pérez de Los Cobos, J; Puig, T; Trujols, J; Valderrama, JC; Valero, S, 2005)	0.95
"94 when plasma from dogs dosed with methadone was evaluated."	( Validation of a high-pressure liquid chromatography and fluorescence polarization immunoassay for the determination of methadone in canine plasma. KuKanich, B; Papich, MG; X Lascelles, BD, 2005)	0.81
" Treatment involved daily administration of either sublingual buprenorphine or oral methadone using flexible dosing of 4-24 mg or 20-100 mg, respectively."	( Buprenorphine versus methadone in the treatment of pregnant opioid-dependent patients: effects on the neonatal abstinence syndrome. Chisholm, CA; Choo, RE; Crocetti, M; Dudas, R; Harrow, C; Huestis, MA; Jansson, LM; Jasinski, DR; Johnson, RE; Jones, HE; Lantz, M; Lester, BM; Milio, L; O'Grady, KE, 2005)	0.87
" No beneficial influence was revealed of methadone dosage or program attendance in itself on the risk of relapse into cocaine."	( Prediction of relapse to frequent heroin use and the role of methadone prescription: an analysis of the Amsterdam Cohort Study among drug users. Geskus, R; Krol, A; Prins, M; Termorshuizen, F; van Ameijden, EJ; van den Brink, W, 2005)	0.84
" Repeated dosing with intrathecal morphine produced a 38-fold increase in the morphine ED50 value."	( Pharmacology of methadone and its isomers. Inturrisi, CE, )	0.48
"LAAM is an effective medication for the treatment of opiate dependence with clinical advantages due not only to the reduction of opiate use but also to the alternate-day dosing schedule."	( Levo-alpha-acetylmethadol (LAAM) versus methadone: treatment retention and opiate use. Anglin, MD; Annon, J; Longshore, D; Rawson, RA, 2005)	0.6
" This close vigilance was aimed at avoiding dosage errors due to variations among individuals in acceptance to previous oral medication."	( Intermittent subcutaneous methadone administration in the management of cancer pain. Centeno, C; Vara, F, 2005)	0.63
" The second part was a cross-sectional study (n = 223 doctors), which consisted of a target-week assessment of 2,694 consecutive patients to determine (a) the severity and problem profiles and treatment targets; (b) the choice and dosage scheme of the substitution drug; (c) past and current interventions, including treatment of comorbid hepatitis C; and (d) cross-sectional differences between the two drugs with regard to comorbidity, clinical course, acceptance/compliance and social integration."	( Buprenorphine and methadone in the treatment of opioid dependence: methods and design of the COBRA study. Apelt, SM; Backmund, M; Bühringer, G; Gastpar, M; Gölz, J; Klotsche, J; Kraus, MR; Pittrow, D; Siegert, J; Soyka, M; Tretter, F; Wittchen, HU, 2005)	0.66
" Dosage adjustment need not be recommended for either methadone or atazanavir when co-administered to patients treated for opiate abuse and HIV disease."	( Lack of an effect of atazanavir on steady-state pharmacokinetics of methadone in patients chronically treated for opiate addiction. Agarwala, S; Andrews, L; Child, M; Daley, L; Friedland, G; O'Mara, E; Schreibman, T; Shi, J; Wang, Y, 2005)	0.81
" The focus of this research is to estimate the percentage of outpatient methadone clients receiving this level of methadone and examine the association between treatment retention and level of methadone dosage as recommended by the NIH expert panel."	( Methadone dosage and retention: an examination of the 60 mg/day threshold. Brady, TM; DeSale, S; Kyeyune, H; Male, A; Salvucci, S; Sikali, E; Sverdlov, LS; Yu, P, 2005)	2
" Such knowledge may help prescribers to determine whether alternative dosing regimens or treatments might be more appropriate in this population."	( Within- and between- subject variability in methadone pharmacokinetics and pharmacodynamics in methadone maintenance subjects. Bochner, F; Foster, DJ; Hanna, J; Salter, A; Somogyi, AA; White, JM, 2005)	0.59
" A protocol favoring higher methadone dosage as appropriate is recommended."	( Factors predicting retention in treatment: 10-year experience of a methadone maintenance treatment (MMT) clinic in Israel. Adelson, M; Peles, E; Schreiber, S, 2006)	0.86
" The reason for the large range in dosage may be multifactorial."	( Free and bound enantiomers of methadone and its metabolite, EDDP in methadone maintenance treatment: relationship to dosage? Eichhorst, JC; Etter, ML; Fern, B; George, S; Graybiel, K; Kapur, B; Lehotay, DC; Selby, P; Wildenboer, W, 2005)	0.62
" Approximately 30-60 mins after the first dosing of methadone, the infant's heart rate decreased from his baseline of 130-140 beats/min to 80-90 beats/min for 30 seconds."	( Bradycardia during methadone therapy in an infant. Tobias, JD; Wheeler, AD, 2006)	0.91
" Special populations in whom a change from the usual dosage regimen may be necessary include pediatric patients, patients with renal failure, the elderly, and pregnant women."	( Pharmacokinetics of methadone. Kern, SE; Lugo, RA; Satterfield, KL, 2005)	0.65
" Nevertheless, many clinicians report that some patients can be stably maintained on lower methadone dosages to optimal effect, and clinic dosing practices vary substantially."	( Determining effective methadone doses for individual opioid-dependent patients. Humphreys, K; Minkel, J; Trafton, JA, 2006)	0.87
" Among patients who achieved heroin abstinence, higher methadone dosages were predicted by having a diagnosis of posttraumatic stress disorder or depression, having a greater number of previous opioid detoxifications, living in a region with lower average heroin purity, attending a clinic where counselors discourage dosage reductions, and staying in treatment longer."	( Determining effective methadone doses for individual opioid-dependent patients. Humphreys, K; Minkel, J; Trafton, JA, 2006)	0.9
" Dosing guidelines should focus more heavily on appropriate processes of dosage determination rather than solely specifying recommended dosages."	( Determining effective methadone doses for individual opioid-dependent patients. Humphreys, K; Minkel, J; Trafton, JA, 2006)	0.65
" Although these specific dosing procedures would not necessarily be used in clinical settings, they provide a procedural template that might be applied safely and effectively with a broader range of treatment-seeking individuals."	( Early impact of methadone induction for heroin dependence: differential effects of two dose sequences in a randomized controlled study. Greenwald, MK, 2006)	0.68
"7 g/70 kg of alcohol in two separate sessions, one 2-3 hours before opioid pharmacotherapy dosing and the other 1-2 hours after dosing."	( Effect of opioid substitution therapy on alcohol metabolism. Clark, NC; Dietze, P; Lenné, MG; Redman, JR, 2006)	0.33
" l-methadone, racemic methadone, and oxycodone had a similar dose-dependent antinociceptive effect, whereas the dose-response curve of morphine was shallower."	( Morphine, oxycodone, methadone and its enantiomers in different models of nociception in the rat. Kalso, E; Kontinen, VK; Kylänlahti, I; Lemberg, K; Viljakka, K; Yli-Kauhaluoma, J, 2006)	1.27
"Limited pharmacokinetic (PK) and pharmacodynamic (PD) data are available to use in methadone dosing recommendations in pediatric patients for either opioid abstinence or analgesia."	( Population-based analysis of methadone distribution and metabolism using an age-dependent physiologically based pharmacokinetic model. Beard, DA; Hines, RN; McCarver, DG; Tong, X; Yang, F, 2006)	0.85
" Equally important perioperative treatment principles are stabilization of physical dependence by substitution with methadone (for heroin addicts) or benzodiazepines/clonidine (for alcohol, sedatives and hypnotics addiction), avoidance of stress and craving, thorough intraoperative and postoperative stress relief by using regional techniques or systematically higher than normal dosages of anesthetics and opioids, strict avoidance of inadequate dosage of analgetics, postoperative optimization of regional or systemic analgesia by non-opioids and coanalgetics and consideration of the complex physical and psychological characteristics and comorbidities."	( [Anesthesia and analgesia in addicts: basis for establishing a standard operating procedure]. Heid, F; Jage, J, 2006)	0.54
" As defined by US federal regulations, IM provides observed methadone dosing and emergency counseling only for a maximum of 120 days."	( A randomized controlled trial of interim methadone maintenance: 10-Month follow-up. Callaman, JM; Highfield, DA; Jaffe, JH; O'Grady, KE; Schwartz, RP, 2007)	0.85
" The pronounced and variable fluctuations in methadone disposition evident in these patients highlight the need for an individualized approach to patient dosing and monitoring."	( Fluctuations in (R,S)-methadone pharmacokinetics and response among long-term methadone maintenance patients. Dyer, KR; Mitchell, TB; Newcombe, D; Somogyi, AA; White, JM, 2006)	0.91
" P-glycoprotein expression and transport activity in brain capillaries from transgenic mice was significantly increased when capillaries were exposed to the hPXR ligands, rifampin and hyperforin, in vitro and when the mice were dosed with rifampin in vivo."	( In vivo activation of human pregnane X receptor tightens the blood-brain barrier to methadone through P-glycoprotein up-regulation. Bauer, B; Hartz, AM; Kalvass, JC; Miller, DS; Olson, ER; Pollack, GM; Yang, X; Zhao, R, 2006)	0.56
" Individually optimized flexible dosing was used for each group, with weekly possible doses of 255-391 mg of LAAM, 56-112 mg of BUP, and 420-700 mg of METH."	( HIV risk behaviors during pharmacologic treatment for opioid dependence: a comparison of levomethadyl acetate [corrected] buprenorphine, and methadone. Bigelow, GE; Brooner, RK; Johnson, RE; Lott, DC; Strain, EC, 2006)	0.54
" The average DAM dosage was 274."	( Controlled trial of prescribed heroin in the treatment of opioid addiction. Carrasco, F; March, JC; Oviedo-Joekes, E; Perea-Milla, E, 2006)	0.33
"To review the literature on methadone deaths and propose evidence-based dosing guidelines."	( Methadone induction doses: are our current practices safe? Kahan, M; Srivastava, A, 2006)	2.07
" The information was collectively considered and, using the best available evidence, translated into safe dosing guidelines for methadone induction."	( Methadone induction doses: are our current practices safe? Kahan, M; Srivastava, A, 2006)	1.98
" Data from the Ontario coroner's office revealed that of deaths that were felt to be attributable to methadone overdose, the majority occurred in those who had consumed diverted methadone: of those deaths within a registered program, the majority occurred during the initial dosing phase."	( Methadone induction doses: are our current practices safe? Kahan, M; Srivastava, A, 2006)	1.99
" This retrospective chart review provides an exploratory examination of newborns treated with either methadone or paregoric for opioid withdrawal and outlines dosage ranges and intervals, side effects, and clinical outcomes of the two regimens."	( A chart review comparing paregoric to methadone in the treatment of neonatal opioid withdrawal. Wunsch, MJ, 2006)	0.82
"To document changes in prescribing practice at a specialized substance misuse service in the UK occurring since the introduction of the 1999 UK National Guidelines on the management of drug misuse, and to explore a possible link between the length of time spent in methadone maintenance therapy (MMT) and the dosage prescribed."	( A six-year evaluation of methadone prescribing practices at a substance misuse treatment centre in the UK. Dickinson, GL; Lagundoye, O; Lennard, MS; Pratt, P; Rostami-Hodjegan, A; Seivewright, N, 2006)	0.82
" The relationship between various measures of dosage and the length of time spent in MMT was investigated."	( A six-year evaluation of methadone prescribing practices at a substance misuse treatment centre in the UK. Dickinson, GL; Lagundoye, O; Lennard, MS; Pratt, P; Rostami-Hodjegan, A; Seivewright, N, 2006)	0.64
"Methadone medical maintenance (MMM) is a model for the treatment of opioid dependence in which a monthly supply of methadone is distributed in an office setting, in contrast to more highly regulated settings where daily observed dosing is the norm."	( A 5-year evaluation of a methadone medical maintenance program. Arnsten, JH; Gourevitch, MN; Harris, KA; Hecht, J; Joseph, H; Juliana, P; Marion, I, 2006)	2.08
" This dosage not only facilitates interaction detection, but also hand encourages communication with the patient."	( [Methadone: from pharmacokinetic profile to clinical pharmacology]. Gury, C; Laqueille, X; Vazquez, V, )	1.04
" The methadone dosage is individualized but highly variable, and program retention rates are low due in part to nonoptimal dosing resulting in withdrawal symptoms and further heroin craving and use."	( ABCB1 genetic variability and methadone dosage requirements in opioid-dependent individuals. Barratt, DT; Coller, JK; Dahlen, K; Loennechen, MH; Somogyi, AA, 2006)	1.14
"Although ABCB1 genetic variability is not related to the development of opioid dependence, identification of variant haplotypes may, after larger prospective studies have been performed, provide clinicians with a tool for methadone dosage individualization."	( ABCB1 genetic variability and methadone dosage requirements in opioid-dependent individuals. Barratt, DT; Coller, JK; Dahlen, K; Loennechen, MH; Somogyi, AA, 2006)	0.81
" Flexible dosing (i."	( Methadone and buprenorphine for the management of opioid dependence: a systematic review and economic evaluation. Burls, A; Connock, M; Day, E; Frew, E; Fry-Smith, A; Jowett, S; Juarez-Garcia, A; Lintzeris, N; Liu, Z; Roberts, T; Taylor, RJ; Taylor, RS, 2007)	1.78
" In direct comparison, a flexible dosing strategy with MMT was found be somewhat more effective in maintaining individuals in treatment than flexible-dose BMT and therefore associated with a slightly higher health gain and lower costs."	( Methadone and buprenorphine for the management of opioid dependence: a systematic review and economic evaluation. Burls, A; Connock, M; Day, E; Frew, E; Fry-Smith, A; Jowett, S; Juarez-Garcia, A; Lintzeris, N; Liu, Z; Roberts, T; Taylor, RJ; Taylor, RS, 2007)	1.78
"The aim of this study was to determine, using methadone pharmacokinetic properties, whether methadone dosage adjustments are needed on initiation of treatment with pegIFN alfa-2b for HCV in methadone-maintained HIV-positive patients."	( Effects of pegylated interferon alfa-2b on the pharmacokinetic and pharmacodynamic properties of methadone: a prospective, nonrandomized, crossover study in patients coinfected with hepatitis C and HIV receiving methadone maintenance treatment. Arnsten, JH; Berk, SI; Du, E; Gourevitch, MN; Litwin, AH; Soloway, I, 2007)	0.82
"Based on the results of this small, prospective, nonrandomized study, pegIFN alfa-2b did not appear to precipitate opioid withdrawal in this sample of methadone-maintained persons with HIV and chronic HCV coinfection; methadone dosage adjustments were unlikely to be needed."	( Effects of pegylated interferon alfa-2b on the pharmacokinetic and pharmacodynamic properties of methadone: a prospective, nonrandomized, crossover study in patients coinfected with hepatitis C and HIV receiving methadone maintenance treatment. Arnsten, JH; Berk, SI; Du, E; Gourevitch, MN; Litwin, AH; Soloway, I, 2007)	0.76
" Depending on the intended indication and dosing regimen, PPL can delay or stop development of a compound in the drug discovery process."	( Evaluation of a published in silico model and construction of a novel Bayesian model for predicting phospholipidosis inducing potential. Gehlhaar, D; Greene, N; Johnson, TO; Pelletier, DJ; Tilloy-Ellul, A, )	0.13
" We initiated active surveillance for cases throughout Australia, a survey of dosing points in NSW, and a case control study of clients receiving methadone syrup (MS) at two clinics."	( An epidemiological investigation into an outbreak of rash illness among methadone maintenance clients in Australia. Alam, NK; Armstrong, PK; Capon, AG; Hailstone, ST; Irvine, K; Jauncey, ME; Kaldor, JM; Mannes, TF; McAnulty, JM; Monger, CK, 2007)	0.77
"The effect of nevirapine once-daily dosing on the pharmacokinetics of methadone and its main metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, was evaluated in ten HIV positive patients on stable methadone therapy."	( Pharmacokinetics of methadone in human-immunodeficiency-virus-infected patients receiving nevirapine once daily. Arroyo, E; Climent-Grana, E; Merino, E; Pérez-Ruixo, JJ; Portilla, J; Valenzuela, B, 2007)	0.9
" It consisted of a 24-day uniform double-blind induction phase followed by single-blind flexible dosing based on structured clinical criteria, for a total of 6 months."	( A stepped care strategy using buprenorphine and methadone versus conventional methadone maintenance in heroin dependence: a randomized controlled trial. Grönbladh, L; Heilig, M; Kakko, J; Nilsson, LH; Rawlings, B; Rück, C; Svanborg, KD; von Wachenfeldt, J, 2007)	0.6
"Steady-state plasma concentrations of (R)- (ie, the active form), (S)-, and (R,S)-methadone were measured in 14 addict patients in methadone maintenance treatment, before and after introduction of quetiapine, administered at a mean dosage of 138 mg/d (SD, 87 mg/d; median, 125 mg/d; range, 50-300 mg/d) during a mean period of 30 days (SD, 8 days; median, 30 days; range, 20-48 days)."	( Increased (R)-methadone plasma concentrations by quetiapine in cytochrome P450s and ABCB1 genotyped patients. Brawand-Amey, M; Brocard, M; Chassot, P; Crettol, S; Eap, CB; Koeb, L; Uehlinger, C, 2007)	0.93
"5mg) may be an effective mechanism for safely dosing this medication in persons with higher levels of physical dependence."	( Sublingual buprenorphine/naloxone precipitated withdrawal in subjects maintained on 100mg of daily methadone. Bigelow, GE; Rosado, J; Strain, EC; Walsh, SL, 2007)	0.56
" The average wholesale price per dosing unit of each drug during each period studied was obtained from internal databases."	( Prescribing patterns and purchasing costs of long-acting opioids over nine years at an academic oncology hospital. Arbuckle, R; Bruera, E; Curry, EA; Hung, F; Palla, S, 2007)	0.34
"Supervised dosing is a cornerstone of tuberculosis treatment."	( Adherence, drug use, and treatment failure in a methadone-clinic-based program of directly administered antiretroviral therapy. Hader, S; Lucas, GM; McCaul, ME; Moore, RD; Mullen, BA; Weidle, PJ, 2007)	0.6
" In addition, methadone dosage requirements were not influenced by CYP2D6 genotypes in these subjects."	( Lack of influence of CYP2D6 genotype on the clearance of (R)-, (S)- and racemic-methadone. Christrup, L; Coller, JK; Foster, DJ; Gillis, D; James, H; Joergensen, C; Somogyi, AA, 2007)	0.93
" This article reviews the World Health Organization recommendations for analgesic therapy in this setting, as well as guidelines for opioid therapy in patients with renal failure or hepatic failure, assessment of pain, dosing strategies in both acute and chronic pain, management of opioid overdose, pain associated with dose-limiting side effects, and pain in the actively dying."	( Practical guide to opioids and their complications in managing cancer pain. What oncologists need to know. Davis, MP; Gamier, P; Lasheen, W, 2007)	0.34
" Nonetheless, the finding of a dose-response effect supports one of the basic principles of clinical practice during detoxification, namely the matching of the medication withdrawal schedule to the pre-admission opiate dose."	( Influence of the dose on the severity of opiate withdrawal symptoms during methadone detoxification. Bearn, J; de Wet, C; Glasper, A; Gossop, M; Reed, L, 2008)	0.58
" The main trends observed were an increasing interest for opioid maintenance treatment by methadone versus buprenorphine high dosage (patients treated by methadone are mainly represented for the first year of the OPPIDUM program), some changes in illicit drugs uses (increase in sniff and decrease in intravenous injection) and changes in the grading of the most consumpted benzodiazepines (decrease in flunitrazepam consumption and increase in clonazepam consumption)."	( [Psychotropic drug addiction: consumption study of specific population by the survey OPPIDUM 2004 from the CEIP network]. Frauger, E; Laurenceau, D; Mallaret, M; Micallef, J; Modelon, H; Thirion, X, )	0.35
" Metropolitan pharmacists dosed greater numbers of OST clients (median = 7) than rural pharmacists (median = 4)."	( Dispensing opioid substitution treatment: practices, attitudes and intentions of community-based pharmacists. Lawrinson, P; Le, PP; Roche, A; Terao, H, 2008)	0.35
"" At that time the etodolac and gabapentin were stopped, and the methadone dosage was increased."	( Edema in a patient receiving methadone for chronic low back pain. Kharlamb, V; Kourlas, H, 2007)	0.87
" These data indicate that chronic HIV treatment may be assisted with plasma concentration monitoring to identify those patients who may require dosage modification and/or regimen adjustment in order to optimize antiretroviral effects."	( Factors associated with altered pharmacokinetics in substance users and non-substance users receiving lopinavir and atazanavir. Boston, N; Brazeau, D; Catanzaro, LM; DiFrancesco, R; Fischl, MA; Forrest, A; Gripshover, B; Higgins, N; Lliguicota, F; Ma, Q; Morse, GD; Reichman, RC; Slish, J; Tooley, K; Zingman, BS, )	0.13
" In subjects whose dosage of levomethadyl or methadone remained fixed over at least 8 weeks, the QTc continued to increase progressively over time (P = ."	( QT-interval effects of methadone, levomethadyl, and buprenorphine in a randomized trial. Bigelow, GE; Haigney, MC; Johnson, RE; Nuzzo, PA; Wedam, EF, 2007)	0.91
" Demerol requires a higher dosage than methadone, but produces less respiratory depression."	( A comparison of certain actions of demerol and methadone. BUCHANAN, OH; TAINTER, ML, 1949)	0.76
" These preliminary results might suggest the involvement of BDNF as a factor to be taken into account in the response to MMT independently of personality traits, environmental cues, methadone dosage and psychiatric comorbidity."	( BDNF variability in opioid addicts and response to methadone treatment: preliminary findings. de Cid, R; Estivill, X; Fonseca, F; Gratacòs, M; Gutierrez, F; Martín-Santos, R; Torrens, M, 2008)	0.79
" The major aims were to compare the efficacy of Bup and Meth in a flexible dosing regimen and to identify possible predictors of outcome."	( Retention rate and substance use in methadone and buprenorphine maintenance therapy and predictors of outcome: results from a randomized study. Koller, G; Kuefner, H; Soyka, M; Zingg, C, 2008)	0.62
"7s during this dosing protocol."	( Antinociceptive effects of high-dose remifentanil in male methadone-maintained patients. Bochner, F; Hay, JL; Somogyi, AA; White, JM, 2008)	0.59
" A dosage of 1-1."	( The disposition and behavioral effects of methadone in Greyhounds. Borum, SL; KuKanich, B, 2008)	0.61
" Four groups were studied: group A included nine heroin addicted subjects, who were still injecting heroin; groups B and C were composed of 12 patients previously addicted to heroin, being treated with methadone (mean dosage 58+/-12."	( Buprenorphine and methadone maintenance treatment of heroin addicts preserves immune function. Franchi, S; Gerra, G; Leccese, V; Panerai, AE; Sacerdote, P; Somaini, L, 2008)	0.87
" Methadone maintenance dosage was generally dispensed daily by registered community pharmacies."	( Comparing drug-related hospital morbidity following heroin dependence treatment with methadone maintenance or naltrexone implantation. Hulse, GK; Ngo, HT; Tait, RJ, 2008)	1.48
"The registration of combination buprenorphine/naloxone, a formulation designed to reduce risk of diversion, has led some Australian jurisdictional authorities to allow treatment without direct observation of dosing for stable, opioid-dependent patients."	( Optimising the benefits of unobserved dose administration for stable opioid maintenance patients: follow-up of a randomised trial. Batey, R; Bell, JR; Mutch, C; Rea, F; Ryan, A, 2008)	0.35
" There was a non-significant trend for people initiated with observed dosing to be better retained during the allocation phase; at 6 months, 13 subjects (22%) from the original unobserved group, and 22 (34%) from the observed group, were retained in treatment (chi2=2."	( Optimising the benefits of unobserved dose administration for stable opioid maintenance patients: follow-up of a randomised trial. Batey, R; Bell, JR; Mutch, C; Rea, F; Ryan, A, 2008)	0.35
" If access to unobserved dosing is to be restricted to stable patients, it appears preferable to initiate dosing with observation and allow unobserved doses for people who successfully stabilize, than to initiate with unobserved doses and transfer unstable patients to observation."	( Optimising the benefits of unobserved dose administration for stable opioid maintenance patients: follow-up of a randomised trial. Batey, R; Bell, JR; Mutch, C; Rea, F; Ryan, A, 2008)	0.35
" The risks and stigma associated with methadone use are known, but difficulties with dosing methadone and lack of an established conversion protocol from other opiates have limited the access for patient populations who could potentially benefit from this medication."	( Consensus guideline on parenteral methadone use in pain and palliative care. Berger, A; Blinderman, CD; Bruera, E; Davis, MP; Derby, S; Inturrisi, C; Kalman, J; Mehta, D; Pappagallo, M; Perlov, E; Shaiova, L, 2008)	0.9
"Review and analyze the evidence base comprising methadone conversion methods and associated dosing ratios for the treatment of pain."	( A systematic review of opioid conversion ratios used with methadone for the treatment of pain. Bain, KT; Weschules, DJ, )	0.63
", and questions relating to appropriate dosing of methadone remain an important issue."	( Personality factors associated with methadone maintenance dose. Behar, E; McHugh, RK; Murray, H; Otto, M; Pratt, E, 2008)	0.87
" Because methadone clinics have been available in China only recently, this study explored the relationship between methadone dosage and client retention in methadone maintenance programmes in Guizhou province."	( Correlates of methadone client retention: a prospective cohort study in Guizhou province, China. Detels, R; Liang, T; Liu, E; Shen, L; Wang, B; Wu, Z; Zhong, H, 2009)	1.13
" The last dosage of maternal methadone just before delivery and the length of treatment for neonatal abstinence syndrome were examined with an analysis of variance model."	( High-dose methadone in pregnant women and its effect on duration of neonatal abstinence syndrome. Cordero, L; Gardner, DK; Lim, S; Prasad, MR; Samuels, P, 2009)	1.05
"All fetal neurobehavioural parameters were suppressed by maternal methadone administration, regardless of dosing regimen."	( Maternal methadone dosing schedule and fetal neurobehaviour. Dipietro, JA; Elko, A; Jansson, LM; Kivlighan, KT; Knauer, H; Velez, M, 2009)	1.01
"0) years, and the average daily methadone dosage was (38."	( [Risk factors associated with continued heroin use during methadone maintenance treatment in Guizhou province, China]. Liang, T; Liu, EW; Roger, D; Shen, LM; Wang, B; Wu, ZY; Zhong, H, 2008)	0.87
"Continued heroin use was common in MMT clinics in Guizhou province; increasing the dosage of methadone and the duration in the treatment program might decrease the continued use of heroin among clients in MMT clinics."	( [Risk factors associated with continued heroin use during methadone maintenance treatment in Guizhou province, China]. Liang, T; Liu, EW; Roger, D; Shen, LM; Wang, B; Wu, ZY; Zhong, H, 2008)	0.81
" Seventeen methadone patients (7 depressed and 10 not depressed) had pharmacokinetic and pharmacodynamic assessments (opioid withdrawal, drug effects, and mood) over one 24-hour dosing interval."	( Major depressive disorder and patient satisfaction in relation to methadone pharmacokinetics and pharmacodynamics in stabilized methadone maintenance patients. Brands, B; Dunn, E; Elkader, AK; Selby, P; Sproule, BA, 2009)	0.98
"To estimate, via meta-analysis, the influence of different methadone dose ranges and dosing strategies on retention rates in methadone maintenance treatment (MMT)."	( A meta-analysis of retention in methadone maintenance by dose and dosing strategy. Bao, YP; Du, C; Epstein, DH; Liu, ZM; Lu, L; Shi, J, 2009)	0.88
" fixed dosing strategy, and duration of follow-up."	( A meta-analysis of retention in methadone maintenance by dose and dosing strategy. Bao, YP; Du, C; Epstein, DH; Liu, ZM; Lu, L; Shi, J, 2009)	0.64
" Additional electrocardiography is recommended if the methadone dosage exceeds 100 mg/d or if patients have unexplained syncope or seizures."	( QTc interval screening in methadone treatment. Haigney, MC; Krantz, MJ; Martin, J; Mehta, D; Stimmel, B, 2009)	0.9
" Dosing regimens varied widely."	( Management of neonatal abstinence syndrome: a national survey and review of practice. Hopewell, J; O'Grady, MJ; White, MJ, 2009)	0.35
" Here, we comprehensively analyzed the DRD2 gene locus, and in addition, the ANKK1 rs1800497C>T single nucleotide polymorphism (SNP), formerly known as 'dopamine D2 receptor Taq1A C>T polymorphism', for associations with the risk of opiate addiction and the methadone dosage requirements."	( Genetic variants altering dopamine D2 receptor expression or function modulate the risk of opiate addiction and the dosage requirements of methadone substitution. Doehring, A; Geisslinger, G; Graff, J; Harder, S; Hentig, Nv; Lötsch, J; Salamat, S; Schmidt, M, 2009)	0.73
"On the basis of an analysis spanning the whole gene locus, from the DRD2 promoter to the ANKK1 rs1800497C>T polymorphism, DRD2 genetic polymorphisms modulate both the risk of opiate addiction, leading to the necessity of methadone substitution therapy, and the course of this therapy in terms of dosage requirements."	( Genetic variants altering dopamine D2 receptor expression or function modulate the risk of opiate addiction and the dosage requirements of methadone substitution. Doehring, A; Geisslinger, G; Graff, J; Harder, S; Hentig, Nv; Lötsch, J; Salamat, S; Schmidt, M, 2009)	0.74
" The greater benefit of HAT in reducing alcohol use may be due to the greater daily frequency of dispensing heroin coupled with a requirement of sobriety at each dosing occasion."	( Effects of heroin-assisted treatment on alcohol consumption: findings of the German randomized controlled trial. Dilg, C; Eiroa-Orosa, FJ; Haasen, C; Reimer, J; Schäfer, I; Soyka, M; Verthein, U, 2009)	0.35
" Participants were mainly satisfied with service provided by the clinic, although had concerns over the inflexibility associated with the clinic atmosphere, frequency of clinic attendance, dosing hours and lack of takeaway doses."	( Satisfaction guaranteed? What clients on methadone and buprenorphine think about their treatment. Bath, N; Lea, T; Madden, A; Winstock, AR, 2008)	0.61
"Early switching from morphine to methadone was a safe and efficient strategy for the reduction of side effects and improvement of analgesia, allowing for a comfortable dosing regimen."	( Early switching from morphine to methadone is not improved by acetaminophen in the analgesia of oncologic patients: a prospective, randomized, double-blind, placebo-controlled study. Cubero, DI; del Giglio, A, 2010)	0.92
" Predictors included binary dosing with methadone in the jail, final dose received (mg), age, gender, race/ethnicity, previous bookings and days in jail."	( The effect of a jail methadone maintenance therapy (MMT) program on inmate recidivism. Lackey, M; Lapham, S; McMillan, GP, 2008)	0.93
" In this review article, there are discussed about pharmacokinetic and pharmacodynamic properties of methadone, clinical symptoms of its overdose, dosage problems, detection of methadone in biological samples, treatment, and causes of methadone overdose-related deaths."	( [Methadone treatment and its dangers]. Jodziūniene, L; Lazauskas, R; Reingardiene, D, 2009)	1.48
" More longitudinal research and studies controlling for the effects of dosage and duration of opioid addiction are necessary to examine whether cognitive ability may improve under long-term MMT."	( Cognitive function in short- and long-term substitution treatment: are there differences? Hennig-Fast, K; Koller, G; Soyka, M; Zingg, C, 2010)	0.36
" Factors as the MMT clinics themselves that the clients visited, daily methadone dosage they took, and the awareness on MMT etc."	( [Factors influencing the rate on retention to methadone maintenance treatment program among heroin addicts in Guizhou, China]. Liang, T; Liu, EW; Shen, LM; Wang, B; Wu, ZL; Zhong, H, 2009)	0.84
"To outline pharmacodynamics, pharmacokinetics, drug interactions, equianalgesic dose ratio with other opioids, dosing rules, adverse effects and methadone clinical studies in patients with cancer pain."	( The role of methadone in cancer pain treatment--a review. Leppert, W, 2009)	0.93
" Dosage for methadone and gender may be the risk factors of craving change."	( [Change and influence factors of craving for patients after 6 month methadone maintenance treatment]. Chen, M; Li, X; Ou, Q; Sun, Z; Tan, H; Zhang, H, 2009)	0.97
" This is in keeping with research showing that this dosage corresponds to optimal opioid receptor blockade."	( Craving and self-efficacy in the first five weeks of methadone maintenance therapy: a daily process study. Barta, WD; Kiene, SM; Kurth, ME; Stein, MD; Tennen, H, 2009)	0.6
"Analysis of 449 diary records nested within 21 participants showed a marked decline in heroin use on days subsequent to the 70 mg methadone dosage plateau."	( Craving and self-efficacy in the first five weeks of methadone maintenance therapy: a daily process study. Barta, WD; Kiene, SM; Kurth, ME; Stein, MD; Tennen, H, 2009)	0.81
"Analgesic efficacy of opioids and dosing protocol have been shown to influence analgesic tolerance."	( Dosing protocol and analgesic efficacy determine opioid tolerance in the mouse. Dighe, SV; Madia, PA; Sirohi, S; Walker, EA; Yoburn, BC, 2009)	0.35
" Dose-response studies were conducted using morphine following treatment."	( Dosing protocol and analgesic efficacy determine opioid tolerance in the mouse. Dighe, SV; Madia, PA; Sirohi, S; Walker, EA; Yoburn, BC, 2009)	0.35
" These results suggest that opioid analgesic tolerance may be increased when sustained release dosing formulations or continuous infusions are employed clinically."	( Dosing protocol and analgesic efficacy determine opioid tolerance in the mouse. Dighe, SV; Madia, PA; Sirohi, S; Walker, EA; Yoburn, BC, 2009)	0.35
" This can be achieved by converting the regular dosage into the equivalent in diazepam and then reducing this dosage by a maximum of 25% a week."	( [Guideline 'Medicinal care for drug addicts in penal institutions']. Arends, MT; de Haan, HA; Klazinga, NS; van Everdingen, JJ; Westra, M, 2009)	0.35
" There was wide variation between pharmacies in the level of supervision provided during supervised buprenorphine dosing and a lack of clarity between pharmacists regarding what behaviors are examples of buprenorphine diversion."	( What is diversion of supervised buprenorphine and how common is it? Lea, T; Sheridan, J; Winstock, AR, 2009)	0.35
"Methadone dosing has been an issue of controversy among clinicians for a long time."	( High dose versus moderate dose methadone maintenance: is there a better outcome? Amar, R; Casarella, J; Drexler, K; Fareed, A; Roberts, M; Sleboda, M; Vayalapalli, S, 2009)	2.08
" At the scene were numerous bottles of methadone, with the chronic dosage of 240 mg 3 times a day."	( Cause of death conundrum with methadone use: a case report. Benson, BE; Letsky, MC; Seifert, SA; Zumwalt, RE, 2011)	0.93
" Patients who were HIV negative at baseline but still secretly using heroine during treatment or accepted low daily average dosage of methadone, had the tendency to drop out."	( [Predictors of retention related factors at the initial methadone maintenance treatment clinics in Guangdong province]. Chen, A; Chen, W; Ling, L; Tan, WK; Xia, YH; Zheng, RJ, 2009)	0.8
" Patients with additional heroin intake over the past 30 days had been treated with a significantly lower L-methadone dosage (P<0."	( Psychiatric comorbidity and additional abuse of drugs in maintenance treatment with L- and D,L-methadone. Baumann, P; Cimander, K; Havemann-Reinecke, U; Jacobs, S; Karg, I; Luedecke, C; Poser, W; Ruether, E; Schneider, U; Wedekind, D, 2010)	0.79
"To date, methadone dosing is still an issue of debate and controversy among clinicians who are involved in methadone maintenance programs."	( Methadone maintenance dosing guideline for opioid dependence, a literature review. Amar, R; Casarella, J; Drexler, K; Fareed, A; Vayalapalli, S, 2010)	2.22
" Of the 140 patients treated at the clinic between 2002 and 2009, 85 were excluded from the study because they had been treated as guests (had been in treatment in other clinics but received methadone dosing temporarily from our clinic), were treated in the clinic for less than 6 months, or dropped out of treatment."	( Onsite QTc interval screening for patients in methadone maintenance treatment. Amar, R; Byrd-Sellers, J; Casarella, J; Drexler, K; Fareed, A; Lutchman, TS; Smith-Cox, J; Vayalapalli, S, 2010)	0.81
"Aspects of methadone maintenance treatment (MMT) delivery, particularly daily dosing practices, are associated with longer retention in treatment."	( Trends in methadone maintenance treatment participation, retention, and compliance to dosing guidelines in British Columbia, Canada: 1996-2006. Anis, AH; Marsh, DC; Nosyk, B; Schechter, MT; Sun, H, 2010)	1.15
" Three times a day dosing schedule was the most typical regimen (57%) while 77% prefer to titrate up on the dosage."	( Methadone: does stigma play a role as a barrier to treatment of chronic pain? Diwan, S; Shah, S, )	1.57
" The average daily dosage of methadone was (48."	( [Risk factors which were associated with heroin use during the methadone maintenance treatment among 1301 patients in 9 cities of China.]. Cao, XB; Li, ZJ; Luo, W; Pang, L; Rou, KM; Wang, CH; Wu, ZY; Xiao, YK; Xu, JS; Yin, WY; Zhang, B; Zhang, CB; Zhang, RM, 2010)	0.89
"01) but fewer dosing visits."	( The cost of concordance with opiate substitution treatment guidelines. Barnett, PG; Humphreys, K; Trafton, JA, 2010)	0.36
" Maternal opiate dosing has been investigated with conflicting results."	( Perinatal risk factors for the neonatal abstinence syndrome in infants born to women on methadone maintenance therapy. Cook, CM; Jones, MP; Liu, AJ; Murray, H; Nanan, R, 2010)	0.58
" Diversion for OST programmes using supervision of dosing is less than diversion of opioids prescribed for pain, which is now a growing public health problem."	( The global diversion of pharmaceutical drugs: opiate treatment and the diversion of pharmaceutical opiates: a clinician's perspective. Bell, J, 2010)	0.36
" A total of 361 opiate-dependent individuals (89% of those eligible, presenting for treatment over 2 years at a drug service in England) received rapid titration then flexible dosing with methadone or buprenorphine; 227 patients chose methadone (63%) and 134 buprenorphine (37%)."	( The SUMMIT trial: a field comparison of buprenorphine versus methadone maintenance treatment. Holland, R; Maskrey, V; Pinto, H; Rumball, D; Swift, L; Wagle, A, 2010)	0.79
"To evaluate the impact of introduction of supervision of methadone dosing on deaths related to overdose of methadone in Scotland and England between 1993 and 2008 while controlling for increased prescribing of methadone."	( Impact of supervision of methadone consumption on deaths related to methadone overdose (1993-2008): analyses using OD4 index in England and Scotland. Bird, SM; Hall, W; Hickman, M; Strang, J, 2010)	0.91
" The decreases in OD4-methadone were closely related to the introduction of supervised dosing of methadone in both countries, first in Scotland (1995-2000) and later in England (1999-2005)."	( Impact of supervision of methadone consumption on deaths related to methadone overdose (1993-2008): analyses using OD4 index in England and Scotland. Bird, SM; Hall, W; Hickman, M; Strang, J, 2010)	0.98
"Introduction of supervised methadone dosing was followed by substantial declines in deaths related to overdose of methadone in both Scotland and England."	( Impact of supervision of methadone consumption on deaths related to methadone overdose (1993-2008): analyses using OD4 index in England and Scotland. Bird, SM; Hall, W; Hickman, M; Strang, J, 2010)	0.96
" Subsequent studies show that the efficacy of buprenorphine sublingual tablet (Subutex®) or buprenorphine/naloxone sublingual tablet (Suboxone®) is equivalent to that of methadone when sufficient buprenorphine doses, rapid induction, and flexible dosing are used."	( Buprenorphine-based regimens and methadone for the medical management of opioid dependence: selecting the appropriate drug for treatment. Gerra, G; Maremmani, I, )	0.61
" There was a dose-response relationship between methadone and neonatal abstinence syndrome."	( Methadone and perinatal outcomes: a retrospective cohort study. Cleary, BJ; Donnelly, JM; Fahey, T; Gallagher, PJ; Murphy, DJ; Strawbridge, JD; White, MJ, 2011)	2.07
"The aim of this study was to compare the transfer of buprenorphine and methadone between maternal and cord blood in women under chronic dosing conditions and to determine if differences exist in the transfer of the two methadone enantiomers."	( (R)- and (S)-methadone and buprenorphine concentration ratios in maternal and umbilical cord plasma following chronic maintenance dosing in pregnancy. Foster, DJ; Gordon, AL; Lopatko, OV; Somogyi, AA; White, JM, 2010)	0.96
" However, many practitioners find methadone offers numerous benefits, including dosing options and duration of analgesia."	( Methadone: marvelous, malevolent, or merely misunderstood? Martin, CM, 2011)	2.09
"The purpose of this study is to assess the incidence of clinically significant neonatal abstinence syndrome (NAS) based on maternal antenatal methadone dosing in women with a history of narcotic dependence."	( Higher maternal doses of methadone does not increase neonatal abstinence syndrome. Bombrys, A; Grier, M; Habli, M; Livingston, J; Pizarro, D; Sibai, B, 2011)	0.87
"Higher maintenance dosing of methadone is not associated with increased rate or severity of NAS or other adverse perinatal outcomes."	( Higher maternal doses of methadone does not increase neonatal abstinence syndrome. Bombrys, A; Grier, M; Habli, M; Livingston, J; Pizarro, D; Sibai, B, 2011)	0.96
" Dosing of fluoxetine/placebo was double blind."	( A randomized controlled trial of fluoxetine in the treatment of cocaine dependence among methadone-maintained patients. Bigelow, GE; Johnson, RE; Silverman, K; Strain, EC; Winstanley, EL, 2011)	0.59
" The objective of this study is to elucidate the reason for the low methadone dosage prescribed in MMT clinics in China."	( A qualitative study exploring the reason for low dosage of methadone prescribed in the MMT clinics in China. Detels, R; Lin, C, 2011)	0.85
"The average dosage prescribed in the 28 clinics was 35 mg/person/day."	( A qualitative study exploring the reason for low dosage of methadone prescribed in the MMT clinics in China. Detels, R; Lin, C, 2011)	0.61
"The findings of the study highlighted the necessity to formulate clear guidelines concerning individualized dosage management and to improve training among service providers' in MMT clinics in China."	( A qualitative study exploring the reason for low dosage of methadone prescribed in the MMT clinics in China. Detels, R; Lin, C, 2011)	0.61
" Importantly, the methadone dosage used in the MMT group was correlated with the FA value in the left splenium of CC and in the right frontal lobe."	( White matter impairment in heroin addicts undergoing methadone maintenance treatment and prolonged abstinence: a preliminary DTI study. Li, Q; Li, W; Wang, W; Wang, Y; Yang, W; Zhu, J, 2011)	0.95
" In the switching study DDD indicated a reduction in analgesic dosing and OMEQ an increase when switching from WHO step II to III."	( Choosing the unit of measurement counts: the use of oral morphine equivalents in studies of opioid consumption is a useful addition to defined daily doses. Borchgrevink, P; Dale, O; Fredheim, O; Hamunen, K; Mellbye, A; Svendsen, K, 2011)	0.37
"OMEQ reflects clinical dosing better than DDD, and can give additional insight into opioid consumption when combined with DDD."	( Choosing the unit of measurement counts: the use of oral morphine equivalents in studies of opioid consumption is a useful addition to defined daily doses. Borchgrevink, P; Dale, O; Fredheim, O; Hamunen, K; Mellbye, A; Svendsen, K, 2011)	0.37
" Harm reduction intensity (HR) was measured by combining injecting drug use, methadone dosage and needle exchange, in different levels of participation, ranging from no/incomplete HR, complete HR to low or no dependence on HR."	( Harm reduction intensity-Its role in HAART adherence amongst drug users in Amsterdam. Coutinho, RA; Lambers, FA; Prins, M; Stolte, IG; van den Berg, CH, 2011)	0.6
" Use of these illicit substances have other consequences like compromising the dosing schedule or adherence / poor compliance to ARTs/ARVs among those enrolled."	( Methadone maintenance therapy as evidence based drug abuse planning in developed countries: can developing countries afford and learn from this experience? Nsimba, SE, 2010)	1.8
" The aim of this study is to analyze methadone dosage in responder and nonresponder patients considering pharmacogenetic and pharmacokinetic factors that may contribute to dosage adequacy."	( Contribution of cytochrome P450 and ABCB1 genetic variability on methadone pharmacokinetics, dose requirements, and response. Cuyàs, E; de la Torre, R; Díaz, L; Farré, M; Fonseca, F; Khymenets, O; Pastor, A; Pizarro, N; Torrens, M, 2011)	0.88
"Adequate methadone dosing in methadone maintenance treatment (MMT) for opioid addiction is critical for therapeutic success."	( CYP2B6 SNPs are associated with methadone dose required for effective treatment of opioid addiction. Adelson, M; Hamon, S; Kreek, MJ; Levran, O; Peles, E; Randesi, M, 2013)	1.09
" Data on methadone dosage at each follow-up interview and the duration of retention in the MMT program were also collected."	( Predictors of the severity of depressive symptoms among intravenous heroin users receiving methadone maintenance treatment in Taiwan: an 18-month follow-up study. Chang, HC; Chung, KS; Wang, PW; Wu, HC; Yeh, YC; Yen, CF; Yen, CN, 2012)	1.02
"These findings provide new insight to the fact that the interindividual variability of methadone dosage requirement is polygenetic and cannot be explained by a single-gene effect."	( Impact of genetic polymorphisms in ABCB1, CYP2B6, OPRM1, ANKK1 and DRD2 genes on methadone therapy in Han Chinese patients. Chiou, MH; Hsieh, TJ; Hsieh, YW; Huang, BH; Huang, CL; Hung, CC; Lane, HY, 2011)	0.82
"Clients from two opioid treatment programs, one implementing ICM and one implementing the TBCM, were recruited to undertake a self-complete survey examining satisfaction with case-management during dosing hours over 7 months."	( Individual versus team-based case-management for clients of opioid treatment services: an initial evaluation of what clients prefer. Curry, K; Day, CA; Demirkol, A; Haber, PS; Hines, S; Lintzeris, N; Tynan, M, 2012)	0.38
" After 72 h, the achieved single dose is maintained, but the dosing interval increases twofold to q 8 h (plus prn q 3 h)."	( Practicability, safety, and efficacy of a "German model" for opioid conversion to oral levo-methadone. Gaertner, J; Klein, C; Nauck, F; Ostgathe, C; Sabatowski, R; Van Aaaken, A; Voltz, R, 2012)	0.6
" The dosing interval was increased correctly after 72 h as demanded by the GMLC in 60% of patients."	( Practicability, safety, and efficacy of a "German model" for opioid conversion to oral levo-methadone. Gaertner, J; Klein, C; Nauck, F; Ostgathe, C; Sabatowski, R; Van Aaaken, A; Voltz, R, 2012)	0.6
"1%, depending on definition applied) in patients receiving relatively low daily doses of methadone therapy, with no evidence of a dose-response relationship."	( Increased incidence of QT interval prolongation in a population receiving lower doses of methadone maintenance therapy. Keenan, E; Kiernan, G; Mahon, NG; McCarthy, C; McGorrian, C; Roy, AK; Sweeney, B, 2012)	0.82
"Buprenorphine/naloxone has recently been introduced in Australia and is available for unsupervised dosing within Queensland."	( Use and misuse of opioid replacement therapies: a Queensland study. Kemp, R; Smirnov, A, 2012)	0.38
" Secondary objectives included characterization (ie, number of dosage and interval changes), duration, and complexity of the methadone taper."	( A pilot study assessing the frequency and complexity of methadone tapers for opioid abstinence syndrome in children discharged to home. Castro, CH; Harrison, DL; Johnson, PN; Miller, JL, )	0.58
" Further research to determine levels of tolerance and psychosocial and pharmacogenetic factors contributing to differences in methadone treatment outcome and dosing in Hmong may provide further insight into opiate addiction and its treatment."	( Superior methadone treatment outcome in Hmong compared with non-Hmong patients. Bart, G; Carlson, G; Hodges, JS; Nolan, C; Wang, Q, 2012)	1
"To evaluate error processing in contrasting opioid treatment samples by finding the relative risk of fatal dosing errors leading to opioid overdose in a controlled cohort of detoxified patients with opioid dependence."	( Opioid-dependent error processing. Fellows-Smith, J, )	0.13
"Naltrexone increases vulnerability to overdose as enhanced opioid effects following neuroanatomical blockade can reverse behavioral tolerance and lead to greater fatal dosing errors on reinstatement of opioid dependence."	( Opioid-dependent error processing. Fellows-Smith, J, )	0.13
" The incidence and duration of NAS did not differ between the two dosage groups."	( Methadone and perinatal outcomes: a prospective cohort study. Carmody, D; Clarke, T; Cleary, BJ; Eogan, M; Fahey, T; Gallagher, PJ; Gleeson, J; McDermott, C; Murphy, DJ; O'Connell, MP; O'Sullivan, A; White, MJ, 2012)	1.82
"Older patients represent a challenge for physicians, as a further factor may play a role in dosing methadone and possibly on successful switching."	( The effect of age on opioid switching to methadone: a systematic review. Bruera, E; Mercadante, S, 2012)	0.86
" Data on methadone dosage at each follow-up point and the duration of retention in the MMT program were also collected."	( Change in quality of life and its predictors in heroin users receiving methadone maintenance treatment in Taiwan: an 18-month follow-up study. Chang, HC; Chung, KS; Wang, PW; Wu, HC; Yeh, YC; Yen, CF; Yen, CN, 2012)	1.03
" A higher dosage of methadone predicted a better QOL."	( Change in quality of life and its predictors in heroin users receiving methadone maintenance treatment in Taiwan: an 18-month follow-up study. Chang, HC; Chung, KS; Wang, PW; Wu, HC; Yeh, YC; Yen, CF; Yen, CN, 2012)	0.94
"9%); and that one should attempt to reduce its treatment dosage as methadone is harmful to one's health (84."	( Misconceptions toward methadone maintenance treatment (MMT) and associated factors among new MMT users in Guangzhou, China. Fan, L; Gu, J; Hao, C; He, W; Lau, JT; Ling, W; Xu, H; Zhao, Y; Zhong, Y, 2012)	0.93
" Different approaches, such as weight-based and formula-based methods, have been used to determine the initial methadone dosing regimen."	( Selection of the initial methadone regimen for the management of iatrogenic opioid abstinence syndrome in critically ill children. Boyles, KA; Johnson, PN; Miller, JL, 2012)	0.89
" Demographic and substance use characteristics, HIV serostatus, family function, depression, and pros and cons of heroin use were collected at baseline, and methadone dosage at each follow-up interview and the duration of retention in the MMT program were also recorded."	( Self-efficacy and HIV risk behaviors among heroin users in Taiwan. Chung, KS; Hsu, ST; Ko, NY; Wang, PW; Wu, HC; Yeh, YC; Yen, CF; Yen, CN, 2012)	0.58
"Drug abusers are known to take a dosage form containing an opioid analgesic and crush, shear, grind, chew, or dissolve it in water or in alcohol, in order to extract the opioid component."	( New immediate release formulation for deterring abuse of methadone. Betancourt, AO; Gosselin, PM; Vinson, RK, )	0.38
"Our findings suggest a role for our rooming-in program in mitigating the relationship between maternal methadone dosage and the need to treat opiate withdrawal in the newborn."	( A rooming-in program to mitigate the need to treat for opiate withdrawal in the newborn. Abrahams, RR; Hodgson, ZG, 2012)	0.59
" In the setting of delayed erectile function after receiving methadone, a trial of dosage reduction and symptomatic treatments may be a reasonable initial approach."	( Erectile dysfunction among male heroin addicts receiving methadone maintenance treatment in Guangdong, China. Chen, J; Chen, W; He, Q; Li, X; Ling, L; Xia, Y, 2012)	0.87
" A picture of one of each infant's eyes was taken under controlled illumination conditions with a standard digital camera just prior to dosing and 0-1, 2-4, 5-7, and 8-10h after dosing."	( Infant pupillary response to methadone administration during treatment for neonatal abstinence syndrome: a feasibility study. Badger, GJ; Gaalema, DE; Heil, SH; Higgins, ST; Johnston, AM; Sigmon, SC, 2012)	0.67
"Mean (±SE) relative pupil diameter decreased significantly after dosing from 41±2% to 29±2%."	( Infant pupillary response to methadone administration during treatment for neonatal abstinence syndrome: a feasibility study. Badger, GJ; Gaalema, DE; Heil, SH; Higgins, ST; Johnston, AM; Sigmon, SC, 2012)	0.67
"Aims of the present investigation were: (i) to assess the prevalence of current smokers and relative smoking status among a large number of heroin addicts attending opioid-substitution therapy prevalence; (ii) to evaluate the relationship between the type (methadone, buprenorphine) and dosage of opioid substitution therapy and nicotine dependence."	( Tobacco addiction and smoking status in heroin addicts under methadone vs. buprenorphine therapy. Amen, G; Casari, R; Chiamulera, C; Faccini, M; Lugoboni, F; Moro, L; Pajusco, B; Quaglio, G, 2012)	0.8
"Among patients receiving methadone maintenance treatment (MMT) for opioid dependence, receipt of unobserved dosing privileges (take homes) and adequate doses (ie, ≥ 80 mg) are each associated with improved addiction treatment outcomes, but the association with acute care hospitalization is unknown."	( Methadone dose, take home status, and hospital admission among methadone maintenance patients. Alford, DP; Chen, C; Cheng, DM; Filippell, T; Pierce, CE; Samet, JH; Walley, AY, 2012)	2.13
" An involvement of aromatase in the disposition of methadone may help explain the difficulty in methadone dosing and suggests a broader role for this catalyst of endogenous steroid metabolism in xenobiotic drug disposition."	( Reduced methadone clearance during aromatase inhibition. Flockhart, DA; Lu, WJ; Thong, N, 2012)	1.07
"The optimal methadone dosing regimen for children undergoing spinal surgery is uncertain because of sparse pediatric pharmacokinetic data and a paucity of analgesic effect data."	( The pharmacokinetics of methadone in adolescents undergoing posterior spinal fusion. Abel, MF; Anderson, BJ; Balireddy, R; Colquhoun, DA; Durieux, ME; Langman, LJ; Stemland, CJ; Thammishetti, S; Witte, J, 2013)	1.08
"Buprenorphine compared with methadone appears to result in less suppression of mean fetal heart rate, fetal heart rate reactivity and the biophysical profile score after medication dosing and these findings provide support for the relative safety of buprenorphine when fetal indices are considered as part of the complete risk-benefit ratio."	( Fetal assessment before and after dosing with buprenorphine or methadone. Coyle, MG; Heil, SH; Jones, HE; Kaltenbach, K; Martin, PR; O'Grady, KE; Salisbury, AL; Stine, SM; Weninger, M, 2012)	0.91
"5, 1, 2, 4, 8, 12 and 24 hours after drug dosing in a separate occasion."	( Contact heat thermal threshold testing in beagle dogs: baseline reproducibility and the effect of acepromazine, levomethadone and fenpipramide. Hoffmann, MV; Kästner, SB; Kietzmann, M; Kramer, S, 2012)	0.59
"Patterns of symptom reports may have clinical implications for maternal and fetal health during pregnancy for OM women including optimization of opioid dosing regimens, education regarding maternal nutritional intake and preventing postnatal depression, thereby ensuring maternal health and fetal development during pregnancy and enhancing mother-infant bonding and healthy child development postnatally."	( Patterns of symptom reporting during pregnancy comparing opioid maintained and control women. Fisk, A; Gordon, AL; Lopatko, OV; Pearson, V; Stacey, H; White, JM; Woods, A, 2012)	0.38
" All dosing was double-blind."	( A randomized investigation of methadone doses at or over 100 mg/day, combined with contingency management. Epstein, DH; Kennedy, AP; Phillips, KA; Preston, KL; Reamer, DA; Schmittner, J, 2013)	0.68
" The ability of participants to enact these 'indigenous harm reduction strategies' was constrained to various degrees by their treatment dosing protocols."	( Methadone diversion as a protective strategy: the harm reduction potential of 'generous constraints'. Harris, M; Rhodes, T, 2013)	1.83
"This study aimed to (i) describe methadone dosing before, during and after pregnancy, (ii) to compare the incidence of neonatal abstinence syndrome (NAS) between those with dose decreases and those with steady or increasing doses and (iii) to describe prescribed medication use among opioid-dependent pregnant women."	( Methadone dosing and prescribed medication use in a prospective cohort of opioid-dependent pregnant women. Carmody, D; Clarke, T; Cleary, BJ; Eogan, M; Fahey, T; Gallagher, PJ; Gleeson, J; McDermott, C; Murphy, DJ; O'Connell, MP; O'Sullivan, A; Reynolds, K; White, MJ, 2013)	2.11
"Of the 117 participants, sufficient dosing data were available for 89 women treated with MMT throughout pregnancy; 36 (40."	( Methadone dosing and prescribed medication use in a prospective cohort of opioid-dependent pregnant women. Carmody, D; Clarke, T; Cleary, BJ; Eogan, M; Fahey, T; Gallagher, PJ; Gleeson, J; McDermott, C; Murphy, DJ; O'Connell, MP; O'Sullivan, A; Reynolds, K; White, MJ, 2013)	1.83
" The primary reasons respondents did not utilize methadone included a lack of knowledge of methadone's pharmacodynamics (39%), effectiveness (39%), and/or dosing equivalence (34%)."	( Attitudes and practices of pediatric oncologists regarding methadone use in the treatment of cancer-related pain: results of a North American Survey. Davies, D; Friebert, S; Kim, M; Roth, M; Wang, D; Zelcer, S, 2013)	0.89
"The relative commonness of reduced-activity CYP2B6 alleles in our study called for attention in terms of dosage requirements for MMT and ARV in Malaysia."	( Haplotypes frequencies of CYP2B6 in Malaysia. Fauzi, H; Ismail, R; Mohamad, N; Musa, N; Talib, N; Zulkafli, MI, )	0.13
"Treatment with higher dosage (≥ 60 mg/day) of methadone seemed to have decreased the possibility of dropout during the follow-up period, whereas frequent illicit drug use (≥ 20%) was important risk factor causing long-term retention."	( [Rate of retention and related factors on patients under methadone maintenance treatment in Beijing: a prospective cohort study]. Liu, GW; Lu, HY; Wang, J, 2012)	0.88
"To investigate the effectiveness of psychosocial services provided by social workers in reducing dropout rate and increasing treatment dosage in methadone maintenance treatment (MMT) users."	( [Effectiveness of intervention services provided by social workers in methadone maintenance treatment clinics]. Fan, LR; Gu, J; Pan, WL; Wang, M; Xu, CJ; Xu, HF; Zhao, YT; Zhong, Y, 2012)	0.81
" The intervention group had higher average treatment dosage than the control group ((56."	( [Effectiveness of intervention services provided by social workers in methadone maintenance treatment clinics]. Fan, LR; Gu, J; Pan, WL; Wang, M; Xu, CJ; Xu, HF; Zhao, YT; Zhong, Y, 2012)	0.61
"The psychosocial interventions provided by social workers were effective in reducing dropout rate, increasing treatment dosage and improving cognitions of MMT users."	( [Effectiveness of intervention services provided by social workers in methadone maintenance treatment clinics]. Fan, LR; Gu, J; Pan, WL; Wang, M; Xu, CJ; Xu, HF; Zhao, YT; Zhong, Y, 2012)	0.61
" High heroin expenses, more severe harm caused by heroin use, perceived lower family support, and lower methadone dosage at 3 months after starting MMT increased the risk of dropout in the follow-up period."	( Predictors for dropping-out from methadone maintenance therapy programs among heroin users in southern Taiwan. Chang, HC; Chen, KY; Chung, KS; Lin, HC; Wang, PW; Wu, HC; Yeh, YC; Yen, CF; Yen, CN, 2013)	0.89
" The current use of MMT in Malaysia in terms of dosage and duration did not pose a significant risk for ED."	( Risk factors of erectile dysfunction in patients receiving methadone maintenance therapy. Abdul Aziz, S; Baharudin, A; Das, S; Ibrahim, N; Midin, M; Mislan, N; Nik Jaafar, NR; Sidi, H, 2013)	0.63
" The minimum plasma concentration in the dosing interval (C(min)), the maximum plasma concentration (Cmax), and the area under the plasma concentration-time curve from h 0 (time of administration) to 24 h postdose (AUC(0-24)) for R-methadone were reduced by 31%, 29%, and 29%, respectively, in the presence of telaprevir."	( Pharmacokinetic interaction between telaprevir and methadone. Boogaerts, G; De Paepe, E; Garg, V; Snoeys, J; van Heeswijk, R; Van Solingen-Ristea, R; Vandevoorde, A; Verboven, P; Vinck, P; Witek, J, 2013)	0.83
" These results may provide a possible explanation for higher methadone dosage requirements in patients carrying variant-type of P-gp and revealed the possible drug-drug interactions in patients who receive concomitant drugs which are also P-gp substrates."	( Functional impact of ABCB1 variants on interactions between P-glycoprotein and methadone. Chiou, MH; Hsieh, YW; Huang, CL; Hung, CC; Lane, HY; Teng, YN, 2013)	0.86
"Prison-based MMT programmes can be effectively implemented but require adequate dosing and measures are needed to improve communication between prison and police authorities, prevent police harassment of MMT clients after their release, and improve systems for tracking release dates."	( Implementing methadone maintenance treatment in prisons in Malaysia. Altice, FL; Kamarulzaman, A; Marcus, R; Wickersham, JA; Zahari, MM, 2013)	0.76
"Les programmes de TMM en milieu carcéral peuvent être efficacement mis en œuvre, mais ils nécessitent un dosage adéquat et des mesures sont nécessaires pour améliorer la communication entre les autorités pénitentiaires et policières, pour éviter les tracasseries policières des patients suivant un TMM après leur libération et pour optimiser les systèmes de suivi des dates de libération."	( Implementing methadone maintenance treatment in prisons in Malaysia. Altice, FL; Kamarulzaman, A; Marcus, R; Wickersham, JA; Zahari, MM, 2013)	0.76
" Therefore, treatment with opioids requires a careful individualization of dosage to achieve an appropriate balance of efficacy and adverse effects and, consequently, avoid toxicity, particularly respiratory depression, sedation and for some, cardiac ventricular fibrillations."	( Pharmacogenetics of opiates in clinical practice: the visible tip of the iceberg. Hajj, A; Khabbaz, L; Laplanche, JL; Peoc'h, K, 2013)	0.39
" Adjusted analyses demonstrated that the individuals with methadone tapering didn't have a greater probability of dropping out compared to those with stable dosage (HR = 1."	( Trends and predictors in methadone maintenance treatment dropout in Shanghai, China: 2005-2011. Asche, CV; Fu, J; Kirkness, CS; Ning, Z; Pan, Q; Ren, J; Ye, X; Zhuang, M, 2013)	0.94
" Increasing the use of methadone tapering after a stable treatment stage with sufficient dosage could be attempted in the MMT program, as well as considering comprehensive interventions among specific populations, such as young, poorly educated, opiate-positive and needle sharing individuals."	( Trends and predictors in methadone maintenance treatment dropout in Shanghai, China: 2005-2011. Asche, CV; Fu, J; Kirkness, CS; Ning, Z; Pan, Q; Ren, J; Ye, X; Zhuang, M, 2013)	1
" Methadone dosing is particularly challenging during initiation of therapy, because of time-dependent increases in hepatic clearance (autoinduction)."	( Mechanism of autoinduction of methadone N-demethylation in human hepatocytes. Campbell, SD; Crafford, A; Kharasch, ED; Williamson, BL, 2013)	1.59
" This study assessed patient perceptions about methadone dosing and the meanings associated with methadone treatment to better support patient adherence to and success in MMT."	( Meaning and methadone: patient perceptions of methadone dose and a model to promote adherence to maintenance treatment. Lubrano, MC; Lucan, SC; Roose, RJ; Sanders, JJ, )	0.77
"Participants held perceptions about methadone dosing that included considerations beyond typical medical parameters used by physicians and other MMT providers to determine appropriate methadone doses."	( Meaning and methadone: patient perceptions of methadone dose and a model to promote adherence to maintenance treatment. Lubrano, MC; Lucan, SC; Roose, RJ; Sanders, JJ, )	0.79
"METODO (methadone efficacy therapy optimization dosage on-going) is a prospective observational study to assess the efficacy and tolerability of methadone in 500 heroin-addicted patients taking a methadone maintenance treatment, enrolled through 2010 to 2011 in five Italian sites, observed over 2 years."	( METODO, a prospective observational study to assess the efficacy and tolerability of methadone in heroin-addicted patients undergoing a methadone maintenance treatment: preliminary results at baseline evaluation. Bignamini, E; D'Egidio, PF; De Vivo, E; González-Saiz, F; Leonardi, C; Lucchini, A; Pieri, MC, 2013)	1.05
" We propose this expanded PBPK model can be used to evaluate different dosing scenarios, during pregnancy, of drugs cleared by single or multiple CYP enzymes."	( Expansion of a PBPK model to predict disposition in pregnant women of drugs cleared via multiple CYP enzymes, including CYP2B6, CYP2C9 and CYP2C19. Ke, AB; Nallani, SC; Rostami-Hodjegan, A; Unadkat, JD; Zhao, P, 2014)	0.4
" Among programs using methadone there was no statistically significant difference in average retention by dosage level, and the 10 highest and lowest dosage programs obtained similar average retention levels after 12 months."	( Retention of participants in medication-assisted programs in low- and middle-income countries: an international systematic review. Abdul-Quader, AS; Arasteh, K; Des Jarlais, D; Feelemyer, J; Hagan, H, 2014)	0.72
"Optimal methadone dosage and service profile is challenging in treatment of opioid dependence."	( Higher methadone doses are associated with lower mortality in patients of opioid dependence in Taiwan. Chen, CH; Chen, PC; Cheng, JJ; Hsieh, CJ; Huang, YF; Liao, DL; Shih, WY, 2013)	1.28
"We describe the case of an intravenous drug user affected by life-threatening Staphylococcus aureus-complicated skin and soft tissue infection with associated bacteraemia who, while on replacement therapy with methadone, required 11 mg/kg/day daptomycin to achieve trough (Cmin) and peak (Cmax) plasma levels similar to those observed with the standard dosage of 6 mg/kg in healthy volunteers (mean ± standard deviation: Cmin 12."	( Daptomycin underexposure in a young intravenous drug user who was affected by life-threatening Staphylococcus aureus-complicated skin and soft tissue infection associated with bacteraemia. Bassetti, M; Cojutti, P; Crapis, M; Pea, F, 2014)	0.59
" Sensitivity analyses indicated a dose-response relationship."	( Time to first treatment interruption in the Chinese methadone maintenance treatment programme. Detels, R; Sullivan, SG; Wu, Z, 2013)	0.64
" Bipolar 1 patients needed a higher methadone dosage in the stabilization phase, but this difference was not statistically significant."	( The long-term outcomes of heroin dependent-treatment-resistant patients with bipolar 1 comorbidity after admission to enhanced methadone maintenance. Akiskal, H; Bacciardi, S; Maremmani, AGI; Maremmani, I; Osso, LD; Pacini, M; Paolo Pani, P; Rovai, L; Rugani, F, 2013)	0.87
" In our current study, we aimed to test the hypothesis that HCV may influence the methadone dosage and its plasma metabolite concentrations in a MMT cohort from Taiwan."	( Hepatitis C virus infection influences the S-methadone metabolite plasma concentration. Chang, YS; Ho, IK; Hsu, YT; Kuo, HW; Liu, SW; Liu, YL; Tsou, HH; Wang, SC; Wu, SL, 2013)	0.88
" No dosage adjustment is needed for MMT when coadministered with DNVr."	( Effect of ritonavir-boosted danoprevir, a potent hepatitis C virus protease inhibitor, on the pharmacokinetics of methadone in healthy subjects undergoing methadone maintenance therapy. Bech, N; Brennan, BJ; Morcos, PN; Moreira, SA; Navarro, MT; Smith, PF, 2014)	0.61
"ECG findings in a convenience sample of 210 methadone-maintained heroin-dependent patients, taking HCV-infection status and methadone dosage into account simultaneously by means of a multiple linear regression model with QTc-interval as the dependent variable."	( QTc prolongation in methadone maintenance--the role of HCV infection. Boesch, L; Bruggmann, P; Falcato, L; Gholami, N; Stohler, R, 2013)	0.97
" Compared to baseline values, the R-methadone mean area under the concentration-time curve to the end of the dosing period (AUCtau) (5,550 versus 6,210 h · ng/ml) and mean maximum concentration of drug in serum (Cmax) (316 versus 337 ng/ml) did not significantly increase in the presence of EVG/COBI."	( Investigation of the interactions between methadone and elvitegravir-cobicistat in subjects receiving chronic methadone maintenance. Bruce, RD; Custodio, JM; Friedland, GH; Kearney, BP; Ramanathan, S; Rhee, MS; Wei, X; Winkle, P, 2013)	0.93
" Eighty per cent of patients were not asked about their ability to swallow solid, oral dosage forms by their physician."	( Challenges of treating patients with chronic pain with dysphagia (CPD): physician and patient perspectives. Carlson, DR; Kopecky, EA; Nalamachu, S; Pergolizzi, JV; Raffa, RB; Taylor, R; Varanasi, RK, 2014)	0.4
"A proportion of patients with chronic pain have dysphagia and cannot swallow solid, oral dosage forms, which creates a serious treatment challenge for pain specialists and other healthcare providers."	( Challenges of treating patients with chronic pain with dysphagia (CPD): physician and patient perspectives. Carlson, DR; Kopecky, EA; Nalamachu, S; Pergolizzi, JV; Raffa, RB; Taylor, R; Varanasi, RK, 2014)	0.4
"The aim of our survey was to assess the dosage and the frequency of side effects in patients with opioid dependency receiving opioid maintenance therapy (OMT)."	( [Methadone and levomethadone - dosage and side effects]. Bald, LK; Bermpohl, F; Gallinat, J; Gutwinski, S; Heinz, A; Riemer, T; Schoofs, N, 2014)	1.31
" The incidence of the side effects irritability and gastrointestinal troubles was significantly higher under OMT with levomethadone, although when an adjustment for dosage was performed."	( [Methadone and levomethadone - dosage and side effects]. Bald, LK; Bermpohl, F; Gallinat, J; Gutwinski, S; Heinz, A; Riemer, T; Schoofs, N, 2014)	1.52
"Levomethadone is dosed significantly higher than methadone."	( [Methadone and levomethadone - dosage and side effects]. Bald, LK; Bermpohl, F; Gallinat, J; Gutwinski, S; Heinz, A; Riemer, T; Schoofs, N, 2014)	1.87
" Methadone treatment was switched to SROM with flexible dosing and vice versa according to period and sequence of treatment."	( Maintenance treatment for opioid dependence with slow-release oral morphine: a randomized cross-over, non-inferiority study versus methadone. Backmund, M; Beck, T; Haasen, C; Reimer, J; Ruckes, C; Schuler, C; Verthein, U; Walcher, S, 2014)	1.52
" This may result in sub-therapeutic dosing creating withdrawal symptoms leading to additional substance use."	( Rates of fetal polydrug exposures in methadone-maintained pregnancies from a high-risk population. Delano, K; Gareri, J; Koren, G, 2013)	0.66
" ECGs have to be made in all patients with methadone therapy 1 week after introducing methadone (or after dosage increases)."	( Prolonged QT interval by methadone: relevance for daily practice? A prospective study in patients with cancer and noncancer pain. Geurts, JW; Patijn, J; van den Beuken-van Everdingen, MH, )	0.7
" Medical and socio-demographic data were gathered and the instruments Opiate Dosage Adequacy Scale (ODAS), European Addiction Severity Index (EuropASI) and the Derogatis Interview for Sexual Functioning - Self Report (DISF-SR) were applied."	( When higher doses in opioid replacement treatment are still inadequate - association to multidimensional illness severity: a cohort study. Bachner, C; Boniakowski, E; Reimer, J; Tietje, W; Verthein, U; Walcher, S; Weber, B, 2014)	0.4
"A high frequency of inadequate dosing was found in this sample of patients on ORT."	( When higher doses in opioid replacement treatment are still inadequate - association to multidimensional illness severity: a cohort study. Bachner, C; Boniakowski, E; Reimer, J; Tietje, W; Verthein, U; Walcher, S; Weber, B, 2014)	0.4
"The lack of methadone pharmacokinetic data in children and neonates restrains dosing to achieve the target concentration in these populations."	( The pharmacokinetics of methadone and its metabolites in neonates, infants, and children. Anderson, BJ; Drover, DR; Hammer, GB; Kern, S; Lugo, RA; Satterfield, K; Stemland, CJ; Tristani-Firouzi, M; Ward, RM, 2014)	1.09
" Research is needed to understand the effectiveness of dosing methods, electrocardiogram monitoring, and other risk mitigation strategies in patients prescribed methadone."	( Methadone overdose and cardiac arrhythmia potential: findings from a review of the evidence for an American Pain Society and College on Problems of Drug Dependence clinical practice guideline. Chou, R; Dana, T; Weimer, MB, 2014)	2.04
" These include lack of evidence on risk factors associated with methadone-overdose deaths and adverse events, limited evidence to evaluate the comparative mortality of methadone versus other opioids, insufficient evidence to fully understand the harms associated with methadone use during pregnancy, and insufficient evidence to determine effects of risk mitigation strategies such as electrocardiogram monitoring, strategies for managing patients with prolonged QTc intervals on screening, urine drug testing, alternative dosing regimens for initiation and titration of therapy, and timing of follow-up."	( Research gaps on methadone harms and comparative harms: findings from a review of the evidence for an American Pain Society and College on Problems of Drug Dependence clinical practice guideline. Chou, R; Weimer, MB, 2014)	0.98
" Other factors such as interaction with drug users and heroin use were marginally significant, while reduced methadone dosage was nonsignificant."	( Situation-specific factors predicting nonadherence to methadone maintenance treatment: a cross-sectional study using the case-crossover design in Guangzhou, China. Chen, L; Gu, J; Hao, C; Hao, Y; Lau, JT; Wang, Z; Xu, H, 2014)	0.86
" Future implementation strategies should focus on higher doses and flexible dosing strategies to optimize program retention and strengthened efforts for clients at higher risk of attrition."	( Methadone treatment for HIV prevention-feasibility, retention, and predictors of attrition in Dar es Salaam, Tanzania: a retrospective cohort study. Bruce, RD; Chang, O; Kaduri, P; Lambdin, BH; Magimba, A; Masao, F; Mbwambo, J; Sabuni, N, 2014)	1.85
"A cohort of 82 patients treated with stable dosage of methadone (mean dosage 65 mg/d) for at least three months was genotyped for five polymorphisms in KCNE1, KCNE2 and KCNH2 genes and had their corrected QT (QTc) assessed."	( KCNH2 polymorphism and methadone dosage interact to enhance QT duration. Bloch, V; Curis, E; Deveaux, LL; Drici, MD; Hajj, A; Ksouda, K; Laplanche, JL; Lépine, JP; Messali, A; Mouly, S; Peoc'h, K; Prince, N; Scherrmann, JM; Vorspan, F, 2014)	0.96
" In a linear regression model, longer QTc interval was associated with methadone dosage and with one genetic factor."	( KCNH2 polymorphism and methadone dosage interact to enhance QT duration. Bloch, V; Curis, E; Deveaux, LL; Drici, MD; Hajj, A; Ksouda, K; Laplanche, JL; Lépine, JP; Messali, A; Mouly, S; Peoc'h, K; Prince, N; Scherrmann, JM; Vorspan, F, 2014)	0.95
" Finally, conflict with daily dosing habits was identified as the primary reason that clients did not accept ART."	( Integrating antiretroviral therapy in methadone maintenance therapy clinics: service provider perceptions. Cao, X; Li, L; Lin, C, 2014)	0.67
"The optimal approach to postpartum dosing among women treated with methadone maintenance is unclear."	( Postpartum changes in methadone maintenance dose. Cheng, DM; Kaminetzky, LB; Pace, CA; Saia, K; Samet, JH; Walley, AY; Winter, M, 2014)	0.95
" Dosage is highly variable and is often controlled by the patient and prescriber according to local and national policy and guidelines."	( Pharmacogenomics of methadone maintenance treatment. Ali, RL; Barratt, DT; Coller, JK; Somogyi, AA, 2014)	0.73
"The methadone dosage left in a sample of 175 bottles recapped after use by the patients taking their maintenance treatment in an addiction treatment program centre was analysed during a 2-week period in March 2013."	( Are empty methadone bottles empty? An analytic study. Bellivier, F; Bloch, V; Bourgogne, E; Brichant-Petitjean, C; Cavalcanti, L; Dupuy, G; Gomberoff, L; Laprévote, O; Lépine, JP; Vorspan, F, 2014)	1.36
" Questionnaire was developed to collect information on demographic characters, behaviours on drug use, sexual behaviour, daily dosage of methadone intake, adherence to MMT, and psychological problems."	( [A case-control study on the causes of new HIV infection among heroin addicts attendees at the methadone maintenance treatment clinics]. Cao, X; He, L; Luo, W; Pang, L; Rou, K; Wang, C; Wu, Z; Zhang, H, 2014)	0.82
" Linear regression models examined predictors of unsupervised dosing in the past month."	( A latent class analysis of self-reported clinical indicators of psychosocial stability and adherence among opioid substitution therapy patients: do stable patients receive more unsupervised doses? Ali, R; Carragher, N; Degenhardt, L; Larance, B; Lintzeris, N; Mattick, RP, 2014)	0.4
" There appears to be a dose-response protective effect of increasing methadone exposure on hepatitis C incidence."	( The impact of methadone maintenance therapy on hepatitis C incidence among illicit drug users. Dias Lima, V; Fairbairn, N; Grebely, J; Kerr, T; Montaner, J; Nolan, S; Wood, E, 2014)	1
" The proposed electrode was successfully applied to the determination of MET in a pharmaceutical dosage form, urine and saliva samples."	( A sensitive electrochemical sensor for rapid determination of methadone in biological fluids using carbon paste electrode modified with gold nanofilm. Afkhami, A; Madrakian, T; Soltani-Felehgari, F, 2014)	0.64
" Patients were grouped into 1 of 3 medication categories based on their selection at intake (methadone [n = 2,738; M dosage = 64."	( A naturalistic comparison of the effectiveness of methadone and two sublingual formulations of buprenorphine on maintenance treatment outcomes: findings from a retrospective multisite study. Copeland, AL; Herschman, PL; Kopak, AM; Polukhina, N; Proctor, SL, 2014)	0.88
" However, due to limited research in this area, methadone dosing remains a challenge, with vigilant dose initiation, adjustment, and monitoring required."	( Therapeutic challenges in cancer pain management: a systematic review of methadone. Afsharimani, B; Good, P; Hardy, J; Haywood, A; Khan, S; Movva, R, 2014)	0.89
" Major findings included that methadone programs presented more regulatory barriers for providers, difficulty with dose verification due to impaired communication, and an over reliance on emergency room dosing leading to unsafe or suboptimal dosing."	( Effects of regulation on methadone and buprenorphine provision in the wake of Hurricane Sandy. Duncan, L; Hansen, H; McClure, B; Mendoza, S; Rotrosen, J, 2014)	0.99
" However, dosage increases, administered as rescue analgesia, promoted adequate pain control even in tramadol group."	( Evaluation of the effects of methadone and tramadol on postoperative analgesia and serum interleukin-6 in dogs undergoing orthopaedic surgery. Cardozo, LB; Cotes, LC; Fantoni, DT; Ferrigno, CR; Kahvegian, MA; Otsuki, DA; Rizzo, MF, 2014)	0.69
" Higher methadone dosage was associated with increased odds of treatment retention, whereas criminal charges and lower self-esteem decreased these odds."	( Psychological predictors of retention in a low-threshold methadone maintenance treatment for opioid addicts: a 1-year follow-up study. Julien, D; Lauzon, P; Milton, D; Perreault, M; Rabouin, D; White, ND, 2015)	1.1
" Cognitive testing took place at 2 time points: study weeks 4 through 5 to assess baseline performance and 10 to 13 weeks later to assess performance during stable dosing (300 mg topiramate or placebo)."	( Topiramate impairs cognitive function in methadone-maintained individuals with concurrent cocaine dependence. Bigelow, GE; Johnson, MW; Mintzer, MZ; Rass, O; Strain, EC; Umbricht, A, 2015)	0.68
" Although individual data showed moderate variability in the exposures between subjects and treatments, there was no evidence of symptoms of opiate overdose or withdrawal either during the coadministration of faldaprevir with methadone or buprenorphine-naloxone or after faldaprevir dosing was stopped."	( Effect of steady-state faldaprevir on the pharmacokinetics of steady-state methadone and buprenorphine-naloxone in subjects receiving stable addiction management therapy. Adeniji, A; Elgadi, M; Huang, F; Joseph, D; Riesenberg, RR; Schobelock, MJ; Vince, BD; Webster, LR, 2015)	0.83
" The retention rates for the 6-year by low (≤ 30 mg/day), medium (31-60 mg/day), and high (>60 mg/day) methadone dosage groups were 20."	( Retention and its predictors among methadone maintenance treatment clients in China: a six-year cohort study. Cao, X; Li, J; Li, L; Lin, C; Luo, W; Pang, L; Rou, K; Wang, C; Wu, Z; Yin, W, 2014)	0.89
" For analysis of the prescribed methadone dose distribution, the patient sample was split into three methadone dosage groups: a low dose group (LDG) (n = 200; < 60 mg/day), a medium dose group (MDG) (n = 273; 60 to 100 mg/day), and a high dose group (HDG) (n = 140; > 100 mg/day)."	( Association between methadone dose and concomitant cocaine use in methadone maintenance treatment: a register-based study. Baumeister, M; Dürsteler-MacFarland, KM; Gerhard, U; Petitjean, SA; Strasser, J; Vogel, M; Walter, M; Wiesbeck, GA, 2014)	1.01
"5, 1, 2, and 24 hours after dosing in subjects with confirmed cocaine use and abstinence."	( The impact of recent cocaine use on plasma levels of methadone and buprenorphine in patients with and without HIV-infection. DInh, AT; Fiellin, DA; Fiellin, LE; Lruie, BS; McCance-Katz, EF; Moody, DE; Tetrault, JM, 2015)	0.67
" Estimates of this model indicated that increase in average methadone dosage was associated with longer retention time."	( Predictors of treatment retention in a major methadone maintenance treatment program in iran: a survival analysis. Heydari, H; Moeeni, M; Pashaei, T; Razaghi, EM; Roshanaei Moghdam, B; Turner, NE, 2014)	0.9
" Single daily dosing is the most common strategy."	( The effect of methadone dose regimen on neonatal abstinence syndrome. Leamon, MH; McCarthy, JJ; Salo, R; Willits, NH, )	0.49
" An analysis of the responses pertaining to the most desired changes required at the center found dosing hours, waiting area and staff shortages to be common."	( A satisfaction survey of opioid-dependent patients with methadone maintenance treatment. Aziz, Z; Chong, NJ, 2015)	0.66
" Plasma TNF-α and IL-6 levels were significantly correlated with the dairy methadone dosage administered, and the IL-1β level was significantly correlated with the duration of methadone maintenance treatment."	( Inflammatory response in heroin addicts undergoing methadone maintenance treatment. Chan, YY; Chang, JL; Lin, JC; Lin, JG; Lo, WY; Yang, SN, 2015)	0.9
", administration route, average dosage and number of consumers) contribute to depict a realistic representation of the phenomenon in the investigated area."	( Data triangulation in the context of opioids monitoring via wastewater analyses. Been, F; Benaglia, L; Delémont, O; Esseiva, P; Gervasoni, JP; Lucia, S, 2015)	0.42
" The interaction of ART and dosage of methadone were connected to the episodes of relapsing and the ART optimism would result in inconsistent condom use."	( [Impact of antiretroviral therapy on drug-using and high risk sexual behaviors among HIV-positive methadone maintenance treatment clients: a qualitative study]. Cao, X; Duan, S; Jin, Y; Luo, W; Qian, X; Rou, K; Tang, R; Wang, C; Willa, D; Wu, Z; Zhang, B; Zhao, Y, 2015)	0.91
"2% among those with a methadone dosage ≥60 mg/day."	( Relationship between plasma concentrations of the l-enantiomer of methadone and response to methadone maintenance treatment. Chericoni, S; Daini, L; Giarratana, T; Meini, M; Moncini, M; Rucci, P; Scaramelli, D; Stefanelli, F, 2015)	0.97
" No difference in maternal methadone dosage and newborns with and without NAS."	( Maternal methadone treatment and neonatal abstinence syndrome. Faisal, M; Li, S; Liu, WF; Singh, K, 2015)	1.13
" There was no difference in methadone dosage between babies with and without NAS."	( Maternal methadone treatment and neonatal abstinence syndrome. Faisal, M; Li, S; Liu, WF; Singh, K, 2015)	1.13
" Given that sub-optimal dosing of BNX increases the risk of diversion, more attention should be paid to providing patients with an optimal medical dose."	( Diversion of opioid maintenance treatment medications and predictors for diversion among Finnish maintenance treatment patients. Alho, H; Kotovirta, E; Launonen, E; Simojoki, K; Wallace, I, 2015)	0.42
" However, to our knowledge, the role of methadone dosing in adherence to antiretroviral therapy (ART) has not yet been investigated."	( Dose-response relationship between methadone dose and adherence to antiretroviral therapy among HIV-positive people who use illicit opioids. Ahamad, K; Dobrer, S; Dong, H; Kerr, T; Lappalainen, L; Milloy, MJ; Montaner, J; Nolan, S; Puscas, C; Wood, E, 2015)	0.96
" In a subanalysis, we observed a dose-response relationship between increasing MMT dose and ART adherence (AOR = 1."	( Dose-response relationship between methadone dose and adherence to antiretroviral therapy among HIV-positive people who use illicit opioids. Ahamad, K; Dobrer, S; Dong, H; Kerr, T; Lappalainen, L; Milloy, MJ; Montaner, J; Nolan, S; Puscas, C; Wood, E, 2015)	0.69
" Adequate methadone dosing is important in retaining clients to maximize HIV treatment benefits and allow for successful linkage to services."	( Implementation and Operational Research: Linkage to Care Among Methadone Clients Living With HIV in Dar es Salaam, Tanzania. Bruce, RD; Lambdin, BH; Masao, F; Mbwambo, J; Sabuni, N; Tran, OC; Ubuguyu, O, 2015)	1.06
" Clinical predictor variables included average methadone dosage (mg/d) and urinalysis drug screen (UDS) findings for opioids and various nonopioid substances at intake and 6 months."	( Predictors of patient retention in methadone maintenance treatment. Copeland, AL; Herschman, PL; Hoffmann, NG; Kopak, AM; Polukhina, N; Proctor, SL, 2015)	0.95
" dose-response relationships of the opioids on cardiovascular metameters in anaesthetised rats in the absence or presence of H1- and H2-receptor antagonism and the μ-opioid antagonist naloxone."	( Contrasting cardiovascular properties of the µ-opioid agonists morphine and methadone in the rat. Angus, JA; Tung, KH; Wright, CE, 2015)	0.65
"A correct dosage for the treatment of NAS was guaranteed."	( Design of pediatric oral formulations with a low proportion of methadone or phenobarbital for the treatment of neonatal abstinence syndrome. Calpena, AC; Clares, B; Mallandrich, M; Provenza, N; Pueyo, B, 2016)	0.67
" The daily methadone dosage ranged from 10 to 120 mg, mostly as syrup."	( Testing for Drugs in Exhaled Breath Collected With ExaBreath in a Drug Dependence Population: Comparison With Data Obtained in Urine After Liquid Chromatographic-Tandem Mass Spectrometric Analyses. Gaulier, JM; Kintz, P; Mathiaux, F; Villéger, P, 2016)	0.82
"47) and higher daily dosage of methadone (≥ 60 mL vs <60 mL; HR=1."	( Trends and risk factors for HIV, HCV and syphilis seroconversion among drug users in a methadone maintenance treatment programme in China: a 7-year retrospective cohort study. Ling, L; Zhang, L; Zou, X, 2015)	0.93
"Based on a methadone dosing protocol, serum concentrations of methadone and its metabolites were assessed by high performance liquid chromatography-tandem mass spectrometry from dried blood spots."	( Pharmacokinetics of Oral Methadone in the Treatment of Neonatal Abstinence Syndrome: A Pilot Study. Akinbi, H; Isemann, B; Mizuno, T; Tabangin, ME; Vinks, AA; Ward, LP; Wiles, JR, 2015)	1.11
" Optimized dosing strategies were developed based on the simulated PK profiles."	( Pharmacokinetics of Oral Methadone in the Treatment of Neonatal Abstinence Syndrome: A Pilot Study. Akinbi, H; Isemann, B; Mizuno, T; Tabangin, ME; Vinks, AA; Ward, LP; Wiles, JR, 2015)	0.72
"The proposed dosing regimen may reduce the cumulative dose of opioid and shorten the length of hospitalization."	( Pharmacokinetics of Oral Methadone in the Treatment of Neonatal Abstinence Syndrome: A Pilot Study. Akinbi, H; Isemann, B; Mizuno, T; Tabangin, ME; Vinks, AA; Ward, LP; Wiles, JR, 2015)	0.72
" Pregnant women were enrolled as part of an open-label non-randomised flexible dosing longitudinal study."	( Visual evoked potential latencies of three-year-old children prenatally exposed to buprenorphine or methadone compared with non-opioid exposed children: The results of a longitudinal study. Baghurst, PA; Sawyer, MG; Spurrier, NJ; Weston, P; Whitham, JN, )	0.35
" There was credible evidence of a strong relationship between opioids and SDB with noted risk factors including use of methadone, high opioid dosing (>200 mg MED) and combining opioids with benzodiazepines."	( Opioid Therapy and Sleep Disorders: Risks and Mitigation Strategies. Cheatle, MD; Webster, LR, 2015)	0.63
"Despite the variability of frequency and consistency of attendance of drug users enrolling in the low-threshold MMT programme in Hong Kong, a consistent pattern could be seen in the proportional distribution of dosage and participation efforts."	( Participation dynamics of a cohort of drug users in a low-threshold methadone treatment programme. Kwan, TH; Lee, SS; Wong, NS, 2015)	0.65
" No difference was observed in total methadone dosage administered (0."	( Cohort Analysis of a Pharmacokinetic-Modeled Methadone Weaning Optimization for Neonatal Abstinence Syndrome. Hall, ES; Meinzen-Derr, J; Wexelblatt, SL, 2015)	0.95
" Insufficient dosage and higher proportion of positive urine samples in the first treatment episode are the key determinants for subsequent client drop-out and re-enrolment."	( Investigation of Repeat Client Drop-Out and Re-Enrolment Cycles in Fourteen Methadone Maintenance Treatment Clinics in Guangdong, China. Li, X; Ling, L; Zhang, D; Zhang, L; Zhao, P; Zou, X, 2015)	0.65
" This is the first study to test the therapeutic effect of daily methadone dosing on the integrity of the cortico-subcortical brain functions as measured by the saccadometry."	( Improvement of saccadic functions after dosing with methadone in opioid addicted individuals. Fareed, A; Feit, J; Gorzelańczyk, EJ; Kunc, M; Walecki, P, 2016)	0.92
"Compared to MMT, TC participants had poorer family support, higher rate of unmarried, higher rate of unemployment, earlier onset of heroin use, longer length of heroin use, and lower daily dosage of heron."	( Comparison of socio-demographic characteristics, substance, and depression among male heroin users attending therapeutic community and methadone maintenance treatment program in Nantou, Taiwan. Chen, VC; Gossop, M; Ho, YF; Lin, TY; Wang, HY; Wu, MH, 2015)	0.62
" Its unique pharmacokinetic profile contributes added complexity; therefore, clinicians should be experienced with its dosing and monitoring."	( Opioid rotation: A case example using methadone in spinal cord injury. Pawasauskas, J, )	0.4
" The differences between doses dispensed immediately before and after the interruption in dosing days ranged from 0 to 7 mg, independently of the length of the interruption or the prescribed dosing level."	( Evaluation of an implementation of methadone maintenance treatment in China. Chawarski, MC; Liu, P; Marienfeld, C; Schottenfeld, R; Wang, X; Zhou, W, 2015)	0.69
"Provision of safe methadone dosing after absences and improving daily attendance are identified as priority improvement areas."	( Evaluation of an implementation of methadone maintenance treatment in China. Chawarski, MC; Liu, P; Marienfeld, C; Schottenfeld, R; Wang, X; Zhou, W, 2015)	1.03
"To learn about the effects of psychological counseling intervention on reducing heroin use, increasing methadone dosage and improving compliance rate of methadone maintenance treatment (MMT)."	( [Effects of psychological counseling intervention on increasing methadone dosage and reducing heroin use among patients receiving methadone maintenance treatment]. Ji, H; Li, J; Li, Y; Wang, C; Wang, H; Wen, Z; Xu, Y; Yang, L; Zhang, B, 2015)	0.87
" Positive rates of urine morphine tests, average days receiving MMT during three months before the intervention and during the intervention, and average daily dosage of methadone during the last week before intervention and during the last week of the intervention programs conducted were recorded and compared."	( [Effects of psychological counseling intervention on increasing methadone dosage and reducing heroin use among patients receiving methadone maintenance treatment]. Ji, H; Li, J; Li, Y; Wang, C; Wang, H; Wen, Z; Xu, Y; Yang, L; Zhang, B, 2015)	0.85
"1%; the average daily dosage of methadone increased from 63."	( [Effects of psychological counseling intervention on increasing methadone dosage and reducing heroin use among patients receiving methadone maintenance treatment]. Ji, H; Li, J; Li, Y; Wang, C; Wang, H; Wen, Z; Xu, Y; Yang, L; Zhang, B, 2015)	0.94
"Intensive psychological counseling intervention was effective in reducing heroin use, increasing methadone dosage and improving compliance rate of MMT among patients receiving MMT."	( [Effects of psychological counseling intervention on increasing methadone dosage and reducing heroin use among patients receiving methadone maintenance treatment]. Ji, H; Li, J; Li, Y; Wang, C; Wang, H; Wen, Z; Xu, Y; Yang, L; Zhang, B, 2015)	0.87
"Higher dosage of methadone is recommended as a way to improve treatment adherence."	( Predictors of Poor Adherence to Methadone Maintenance Treatment in Yunnan Province, China. Guo, J; Li, J; Li, X; Shen, J; Wang, M; Wang, X; Zhang, G, )	0.75
" Subjects established on daily methadone OST (mean dose 60 mg/day) were switched to morphine slow-release capsules, dosed at 4× the previous total daily methadone dose, for 6 days, then given morphine syrup dosed q3h."	( Switching Opioid-Dependent Patients From Methadone to Morphine: Safety, Tolerability, and Methadone Pharmacokinetics. Cape, G; Devane, J; Friedhoff, L; Glue, P; Gray, A; Harland, S; Howes, J; Hung, CT; Hung, N; Lam, F; Lockhart, M; Tunnicliff, D; Weis, H, 2016)	0.99
" In addition, the change of FA in the overlapping regions was positively correlated with the accumulated dosage of methadone use, the RD value in Scan2 and non-planning impulsiveness (NPI) measured at follow-up."	( Methadone-induced Damage to White Matter Integrity in Methadone Maintenance Patients: A Longitudinal Self-control DTI Study. Chen, J; Li, Q; Li, W; Li, Y; Li, Z; Liu, J; Liu, Y; Wang, W; Wang, Y; Yan, X; Ye, J; Zhu, J, 2016)	2.09
" The mean current daily dosage of methadone was 77."	( Report: Demographic profiles and sleep quality among patients on methadone maintenance therapy (MMT) in Malaysia. Choon, TS; Ismail, R; Mohamad, N; Mohd Yasin, MA; Musa, N; Siong, LC; Zahari, Z, 2016)	0.95
" A total of 554 heroin addicts in accordance with the inclusion criteria from 81 streets in 12 districts of Shanghai, China were divided into 4 groups: group 1--daily dosage taken orally of 60 mL of methadone or under combined with psychological counseling and social supports (n = 130); group 2--daily dosage taken orally of over 60 mL of methadone combined with psychological counseling and social supports (n = 50); group 3--JTT (Jitai tablets) combined with psychological counseling and social supports (n = 206); group 4--JTT combined with social supports (n = 168)."	( Factors Associated with Relapse among Heroin Addicts: Evidence from a Two-Year Community-Based Follow-Up Study in China. Feng, XS; Jiang, HF; Rong, C; Zhang, J; Zhang, JC; Zhang, LJ; Zhang, RW, 2016)	0.62
" Accuracy in MEMS caps openings was customized to each participant's unique required dosing schedule."	( Comparison of methods to assess psychiatric medication adherence in methadone-maintained patients with co-occurring psychiatric disorder. Brooner, RK; Dunn, KE; King, VL, 2016)	0.67
"A region-wide cross-sectional study was performed focusing on dosage and duration of treatment."	( Opioid tolerance in methadone maintenance treatment: comparison of methadone and levomethadone in long-term treatment. Bermpohl, F; Gutwinski, S; Riemer, TG; Schoofs, N; Stuke, H; Wiers, CE, 2016)	0.76
" We found a significant correlation between dosage and duration of treatment, both in a conjoint analysis for the two substances racemic methadone and levomethadone and for each substance separately."	( Opioid tolerance in methadone maintenance treatment: comparison of methadone and levomethadone in long-term treatment. Bermpohl, F; Gutwinski, S; Riemer, TG; Schoofs, N; Stuke, H; Wiers, CE, 2016)	0.96
"The aim of this study was to assess the incidence of OST (high dosage buprenorphine (HDB) and methadone (MTD)) shopping behavior and identify associated risk factors, and its impact on mortality."	( Incidence of high dosage buprenorphine and methadone shopping behavior in a retrospective cohort of opioid-maintained patients in France. Authier, N; Brousse, G; Chenaf, C; Delorme, J; Kabore, JL; Laporte, C; Mulliez, A; Pereira, B; Tremey, A; Zenut, M, 2016)	0.92
"Shopping behavior was only found in high dosage buprenorphine patients and concerned almost one out ten patients."	( Incidence of high dosage buprenorphine and methadone shopping behavior in a retrospective cohort of opioid-maintained patients in France. Authier, N; Brousse, G; Chenaf, C; Delorme, J; Kabore, JL; Laporte, C; Mulliez, A; Pereira, B; Tremey, A; Zenut, M, 2016)	0.7
" We wanted to explore if the Opiate Dosage Adequacy Scale (ODAS) is a helpful instrument in methadone titration."	( The opiate dosage adequacy scale for identification of the right methadone dose--a prospective cohort study. Koc, J; Reichel, V; Reimer, J; Schlote, F; Verthein, U; Walcher, S, 2016)	0.89
" Compared to adequately dosed patients, inadequately dosed patients benefited more, in that they showed greater improvements in ODAS scores, had higher increases in methadone dose, and partially experienced more advanced sexual functioning."	( The opiate dosage adequacy scale for identification of the right methadone dose--a prospective cohort study. Koc, J; Reichel, V; Reimer, J; Schlote, F; Verthein, U; Walcher, S, 2016)	0.87
"BMI increased over time, but independent of methadone dosage and blood levels."	( Risk factors for weight gain during methadone maintenance treatment. Adelson, M; Peles, E; Sason, A; Schreiber, S, )	0.67
" All opioid dependent patients were stabilized in treatment, defined as having been enrolled in the program for more than one month with no change of methadone dosage over the past one month."	( Comparison of Pain Tolerance between Opioid Dependent Patients on Methadone Maintenance Therapy (MMT) and Opioid Naive Individuals. Ibrahim, MA; Ismail, R; Lee, CS; Lee, YY; Mohamad, N; Mohd Yasin, MA; Musa, N; Tan, SC; Zahari, Z, 2016)	0.87
" Dosage increase(26."	( [Overdose of heroin and influencing factors in intravenous drug users in parts of Yunnan]. Cao, XB; Luo, W; Wu, ZY; Zhang, B; Zhou, Y, 2016)	0.43
"Opioid conversion to methadone is commonly practiced at our institution; however, dosing was significantly lower compared to adult conversion ratios, and more than 40 percent of children were undermedicated."	( Methadone conversion in infants and children: Retrospective cohort study of 199 pediatric inpatients. Fife, A; Flood, A; Friedrichsdorf, SJ; Postier, A, )	1.89
" Medical records from a 4-year period (September 2006 to October 2010) at a pediatric oncology institution were reviewed, and correlations were tested between cardiac conduction and methadone dosage and duration of therapy, electrolyte levels, renal and hepatic dysfunction, and concurrent medications."	( Methadone prolongs cardiac conduction in young patients with cancer-related pain. Anghelescu, DL; Baker, JN; Faughnan, LG; Mahoney, DP; Patel, RM; Pei, D; Steen, BD; Trujillo, L, )	1.77
"At a clinically effective analgesic dose, methadone dosage and duration were not correlated with QTc prolongation, even in the presence of other risk factors, suggesting that methadone use may be safe in pediatric populations."	( Methadone prolongs cardiac conduction in young patients with cancer-related pain. Anghelescu, DL; Baker, JN; Faughnan, LG; Mahoney, DP; Patel, RM; Pei, D; Steen, BD; Trujillo, L, )	1.84
"Data analysis from observatory for pharmacodependency in ambulatory medicine survey (observation des pharmacodépendances en médecine ambulatoire [OPEMA]) program in 2013 of the subjects under high dosage buprenorphine (HDB) and methadone prescribed or obtained illegally reported by GPs in France."	( [Characteristics of subjects under opiate maintenance treatment in primary care using the OPEMA data 2013]. Amaslidou, D; Frauger, E; Gentile, G; Giocanti, A; Micallef, J; Orleans, V; Pauly, V; Thirion, X, 2016)	0.62
"Survey concerned consumers with 862, 433 and 429 of high dosage buprenorphine and respectively methadone."	( [Characteristics of subjects under opiate maintenance treatment in primary care using the OPEMA data 2013]. Amaslidou, D; Frauger, E; Gentile, G; Giocanti, A; Micallef, J; Orleans, V; Pauly, V; Thirion, X, 2016)	0.65
" Use of conversion tables to guide selection of opioid agonist dosage may compromise patient safety."	( Opioid agonist doses for oxycodone and morphine dependence: Findings from a retrospective case series. Bruno, R; Degenhardt, L; Demirkol, A; Lintzeris, N; Nielsen, S, 2017)	0.46
"This study investigated the associations of ABCB1 polymorphisms and serum methadone concentration over the 24-hour dosing interval in opioid-dependent patients on methadone maintenance therapy (MMT)."	( Relationship between ABCB1 polymorphisms and serum methadone concentration in patients undergoing methadone maintenance therapy (MMT). Ibrahim, MA; Ismail, R; Lee, CS; Lee, YY; Mohamad, N; Mohd Yasin, MA; Musa, N; Tan, SC; Zahari, Z, 2016)	0.92
"Our results revealed an association of CGC/TTT diplotype (1236C>T, 2677G>T/A, and 3435C>T) with dose-adjusted serum methadone concentration over the 24-hour dosing interval."	( Relationship between ABCB1 polymorphisms and serum methadone concentration in patients undergoing methadone maintenance therapy (MMT). Ibrahim, MA; Ismail, R; Lee, CS; Lee, YY; Mohamad, N; Mohd Yasin, MA; Musa, N; Tan, SC; Zahari, Z, 2016)	0.9
"There was an association between the CGC/TTT diplotype of ABCB1 polymorphisms and serum methadone concentration over the 24-hour dosing interval among patients on MMT."	( Relationship between ABCB1 polymorphisms and serum methadone concentration in patients undergoing methadone maintenance therapy (MMT). Ibrahim, MA; Ismail, R; Lee, CS; Lee, YY; Mohamad, N; Mohd Yasin, MA; Musa, N; Tan, SC; Zahari, Z, 2016)	0.91
" It is commercialized as a racemic mixture with considerable variability in the pharmacokinetics and pharmacodynamics between individuals that can affect dose-response and toxicological profile."	( Metabolomics of methadone: clinical and forensic toxicological implications and variability of dose response. Dinis-Oliveira, RJ, 2016)	0.78
"The effectiveness of methadone maintenance treatment is beyond any doubt, but there remains some incertitude about the appropriate and effective dosage and the objectives that should be achieved by this therapy."	( Methadone dosage and its relationship to quality of life, satisfaction, psychopathology, cognitive performance and additional consumption of non-prescribed drugs. MethaQoL, G; Pedrero-Pérez, EJ, 2016)	2.2
" This case highlights that patients whose goal is not abstinence can be successfully treated for acute medical illnesses and comorbid substance use disorders using harm reduction approaches, including appropriate dosing of pharmacotherapy."	( Treatment of opioid use disorder in an innovative community-based setting after multiple treatment attempts in a woman with untreated HIV. Ahamad, K; Fairgrieve, C; Joe, R; Voon, P, 2016)	0.43
" Regression analyses revealed that methadone dosage and time since dosing accounted for a significant proportion of the variance in cognitive flexibility, while the total amount of methadone administered was able to predict deficits in WM, methadone treatment duration predicted psychomotor speed, and time since dosing predicted decision-making ability."	( Hot and cold executive functions in pure opioid users undergoing methadone maintenance treatment: Effects of methadone dose, treatment duration, and time between last methadone administration and testing. Barahmand, U; Khazaee, A; Mohammadi, K; Tavakolian, E, )	0.65
"Although the DRD2 TaqI B genotype was not associated with methadone use requirements, borderline index was revealed as a potential predictive marker for the adjustment of methadone dosage requirements in heroin addicts."	( Relationship among methadone dose, polymorphisms of dopamine D2 receptor and tri-dimensional personality questionnaire in heroin-addicted patients. Chiang, TA; Huang, CS; Huang, MW; Lo, PY, 2016)	1.01
" Thus, monitoring plasma methadone levels is unlikely to be effective for guiding dosing decisions in situations where compliance with MMT is already very high or when the methadone dose is no longer the dominant factor in determining the clinical outcome."	( Dose, Plasma Level, and Treatment Outcome Among Methadone Patients in Shanghai, China. Alfonso, A; Du, J; Hillhouse, M; Jiang, H; Ling, W; Pan, S; Wang, J; Yuan, W; Zhao, M; Zhou, Z, 2016)	0.99
", their race) may play a key role in explaining variations in methadone dosage across programs and patients."	( The Role of Program Directors in Treatment Practices: The Case of Methadone Dose Patterns in U.S. Outpatient Opioid Agonist Treatment Programs. D'Aunno, T; Frimpong, JA; Shiu-Yee, K, 2017)	0.93
" Data were collected from medical screening forms and jail databases and included demographic variables, dates of admission and release, number of doses and total dosage of methadone if applicable, reason for incarceration, and the date of rebooking and nature of offense, if it occurred."	( Community-Based Methadone Maintenance in a Large Detention Center is Associated with Decreases in Inmate Recidivism. Guerin, P; McCrady, BS; Owens, M; Westerberg, VS, 2016)	0.97
" Furthermore, dosing of neuropathic medications is limited by renal function, which is often impaired in the elderly due to both normal aging and renal disease."	( Use of Methadone as an Adjuvant Medication to Low-Dose Opioids for Neuropathic Pain in the Frail Elderly: A Case Series. Grief, CJ; Grossman, D; Kirstein, A; Pan, J; Vu Bach, T, 2016)	0.89
" Recommendations are made for further research into physician/patient interactions and into optimal dosing of methadone and buprenorphine to minimize maternal/fetal withdrawal."	( Opioid dependence and pregnancy: minimizing stress on the fetal brain. Fassbender, C; Finnegan, LP; Leamon, MH; McCarthy, JJ, 2017)	0.67
" The aim of this study was to assess the trends in the prevalence of doctor shopping for high dosage buprenorphine (HDB) and methadone (MTD) from 2004 to 2014 by using the French Health Insurance claims."	( [Trend in buprenorphine and methadone shopping behavior in France from 2004 to 2014]. Authier, N; Brousse, G; Chenaf, C; Delorme, J; Kabore, JL; Kernisant, M; Laporte, C; Zenut, M, 2016)	0.93
"This was a cross-sectional study of patients treated by OMT (High Dosage Buprenorphine or Methadone) between 2004 and 2014 from a representative sample of the French Health Insurance claims."	( [Trend in buprenorphine and methadone shopping behavior in France from 2004 to 2014]. Authier, N; Brousse, G; Chenaf, C; Delorme, J; Kabore, JL; Kernisant, M; Laporte, C; Zenut, M, 2016)	0.95
" As part of the original study protocol, participants completed a comprehensive battery to assess satisfaction with MMT, psychological distress, opinion of methadone as a medication, participation in dosage decisions, and perception of dose adequacy."	( Patient perception of methadone dose adequacy in methadone maintenance treatment: The role of perceived participation in dosage decisions. Alcaraz, S; Batlle, F; Duran-Sindreu, S; González-Saiz, F; Manresa, MJ; Pérez de Los Cobos, J; Trujols, J, 2017)	0.97
"Multivariate binary logistic regression showed that the only variable independently associated with the likelihood of a patient perceiving methadone dose as inadequate was the variable perceived-participation in methadone dosage decisions (OR=0."	( Patient perception of methadone dose adequacy in methadone maintenance treatment: The role of perceived participation in dosage decisions. Alcaraz, S; Batlle, F; Duran-Sindreu, S; González-Saiz, F; Manresa, MJ; Pérez de Los Cobos, J; Trujols, J, 2017)	0.97
"Patient participation in methadone dosage decisions was predictive of perceived adequacy of methadone dose beyond the contribution of other socio-demographic, clinical, and MMT variables."	( Patient perception of methadone dose adequacy in methadone maintenance treatment: The role of perceived participation in dosage decisions. Alcaraz, S; Batlle, F; Duran-Sindreu, S; González-Saiz, F; Manresa, MJ; Pérez de Los Cobos, J; Trujols, J, 2017)	1.07
"Patient participation in methadone dosage decision-making is valuable for developing a genuinely patient-centred MMT."	( Patient perception of methadone dose adequacy in methadone maintenance treatment: The role of perceived participation in dosage decisions. Alcaraz, S; Batlle, F; Duran-Sindreu, S; González-Saiz, F; Manresa, MJ; Pérez de Los Cobos, J; Trujols, J, 2017)	1.07
"Methadone is effective for the treatment of chronic pain, but its unique pharmacology requires additional considerations with dosing and monitoring."	( Methadone Inpatient and Discharge Prescribing Patterns for Pain at an Academic Health System. Atayee, RS; Edmonds, KP; Hollenbach, KA; Hur, GH; Karimian, P, 2017)	3.34
" A wide variety of methadone dosing and taper strategies were reported."	( The use of methadone to facilitate opioid weaning in pediatric critical care patients: a systematic review of the literature and meta-analysis. Dervan, LA; Watson, RS; Wolf, FM; Yaghmai, B, 2017)	1.17
" Less is known about ideal pain management and postpartum dosing regimens."	( Treating Women Who Are Pregnant and Parenting for Opioid Use Disorder and the Concurrent Care of Their Infants and Children: Literature Review to Support National Guidance. Campopiano, M; Hayashi, S; Isaacs, K; Jones, HE; Klaman, SL; Leopold, A; Perpich, J; Vender, J, )	0.13
"The objective of this systematic review is to compare the effectiveness of OST with supervised dosing relative to dispensing of medication for off-site consumption."	( Supervised dosing with a long-acting opioid medication in the management of opioid dependence. Gowing, L; Saulle, R; Vecchi, S, 2017)	0.46
"Randomised controlled trials (RCTs), controlled clinical trials (CCTs), and prospective controlled cohort studies, involving people who are receiving OST (methadone, buprenorphine) and comparing supervised dosing with dispensing of medication to be consumed away from the dispensing point, usually without supervision."	( Supervised dosing with a long-acting opioid medication in the management of opioid dependence. Gowing, L; Saulle, R; Vecchi, S, 2017)	0.65
" There is uncertainty about the effects of supervised dosing compared with unsupervised medication due to the low and very low quality of the evidence for the primary outcomes of interest for this review."	( Supervised dosing with a long-acting opioid medication in the management of opioid dependence. Gowing, L; Saulle, R; Vecchi, S, 2017)	0.46
" The effectiveness of our proposal is shown by simulations comparing it to other dissimilarity measures and by a real application to methadone dosage maintenance levels."	( Dissimilarity for functional data clustering based on smoothing parameter commutation. Hennig, C; Li, YF; Lin, CJ; Tzeng, S, 2018)	0.68
" However, frequent dosing requirements and potential for misuse and drug diversion contribute to significant complications with treatment adherence for available formulations."	( Buprenorphine implants in medical treatment of opioid addiction. Chavoustie, S; Dammerman, R; Darwish, M; Frost, M; Owen, J; Sanjurjo, V; Snyder, O, 2017)	0.46
" This was then compared with actual dosing as ordered by clinicians and received by the patient."	( Methadone Dose Selection for Treatment of Pain Compared with Consensus Recommendations. Ajayi, TA; Atayee, RS; Edmonds, KP; Karimian, P, 2017)	1.9
" Final methadone dose as received by two-thirds of patients was below the dosing target calculated by EPERC and Friedman guidelines by an average of 35 mg."	( Methadone Dose Selection for Treatment of Pain Compared with Consensus Recommendations. Ajayi, TA; Atayee, RS; Edmonds, KP; Karimian, P, 2017)	2.35
"These findings may question the best approach to clinical application of EPERC and Friedman methods and call for more research to determine the safest, lowest, and most effective methadone target dosing selection."	( Methadone Dose Selection for Treatment of Pain Compared with Consensus Recommendations. Ajayi, TA; Atayee, RS; Edmonds, KP; Karimian, P, 2017)	2.09
" Multivariate linear regression to assess correlates of HCV knowledge post-intervention revealed that optimal dosage of MMT and having had an HIV test in the past year significantly increased HCV knowledge."	( Evaluation of a hepatitis C education intervention with clients enrolled in methadone maintenance and needle/syringe programs in Malaysia. Ali, SH; Altice, FL; Kamarulzaman, A; Mukherjee, TI; Pillai, V; Wickersham, JA, 2017)	0.68
" The results confirm the importance of adequate OAT dosing (≥60mg of methadone, ≥8mg of buprenorphine)."	( Retention in medication-assisted treatment programs in Ukraine-Identifying factors contributing to a continuing HIV epidemic. Altice, FL; Chernova, O; Dumchev, K; Dvoryak, S; Morozova, O, 2017)	0.69
" The saliva-to-plasma concentration ratio was compared versus the dose administered and the time after dosing for both enantiomers."	( Can Saliva and Plasma Methadone Concentrations Be Used for Enantioselective Pharmacokinetic and Pharmacodynamic Studies in Patients With Advanced Cancer? George, R; Good, P; Hardy, J; Haywood, A; Hennig, S; Khan, S; Norris, R, 2017)	0.77
" Although the saliva-to-plasma ratio of the concentration of methadone enantiomers was stable across the dosing range, due to the variability in individual saliva-to-plasma ratios, saliva sampling may not be a valid substitute in pharmacokinetic studies of methadone in cancer."	( Can Saliva and Plasma Methadone Concentrations Be Used for Enantioselective Pharmacokinetic and Pharmacodynamic Studies in Patients With Advanced Cancer? George, R; Good, P; Hardy, J; Haywood, A; Hennig, S; Khan, S; Norris, R, 2017)	1.01
" Ensuring that methadone dosing is adequate and reducing or eliminating the co-payment fee for those who cannot afford it could improve retention."	( A longitudinal and case-control study of dropout among drug users in methadone maintenance treatment in Haiphong, Vietnam. Han, PV; Khue, PM; Lindan, C; Tham, NT; Thanh Mai, DT; Thuc, PV; Thuc, VM, 2017)	1.04
" While previous research suggested low dosing of methadone and high rates of discontinuation of MMT among PWID in Thailand, little is known about patients' lived experiences with MMT in this setting."	( Barriers to retention in methadone maintenance therapy among people who inject drugs in Bangkok, Thailand: a mixed-methods study. Ayutthaya, PPN; Hayashi, K; Kaplan, K; Kerr, T; Small, W; Suwannawong, P; Ti, L, 2017)	1.01
"Among 158 survey participants, a median dosage of methadone was 30 mg/day (interquartile range 20-50)."	( Barriers to retention in methadone maintenance therapy among people who inject drugs in Bangkok, Thailand: a mixed-methods study. Ayutthaya, PPN; Hayashi, K; Kaplan, K; Kerr, T; Small, W; Suwannawong, P; Ti, L, 2017)	1.01
" Lower methadone dosage was significantly associated with improvements in the physical, psychological, and environmental domains."	( Evaluation of Methadone Treatment in Malaysia: Findings from the Malaysian Methadone Treatment Outcome Study (MyTOS). Abdullah, N; Ali, N; Aziz, SA; Danaee, M; Mahmud, M; Mi, NC; Nordin, S; Paranthaman, V; Yee, A, 2018)	1.3
"To evaluate the potential association of the genetic polymorphisms in ABCB1, ARRB2, DRD1 and OPRD1 genes with methadone dosage requirement among Han Chinese opioid-dependent patients."	( Impact of SNP-SNP interaction among ABCB1, ARRB2, DRD1 and OPRD1 on methadone dosage requirement in Han Chinese patients. Feng, X; Hu, P; Li, X; Liu, Z; Luo, R; Luo, X; Luo, Z; Qin, S, 2017)	0.9
" A 3-locus SNP-SNP interaction pattern (rs1128503 in ABCB1, rs529520 in OPRD1 and rs1045280 in ARRB2) was significantly associated with the methadone dosage requirement (p = 0."	( Impact of SNP-SNP interaction among ABCB1, ARRB2, DRD1 and OPRD1 on methadone dosage requirement in Han Chinese patients. Feng, X; Hu, P; Li, X; Liu, Z; Luo, R; Luo, X; Luo, Z; Qin, S, 2017)	0.89
"Our results suggested that specific OPRD1 variants and interaction among polymorphisms in ABCB1, OPRD1 and ARRB2 genes contributes to methadone dosage requirement in Han Chinese opioid-dependent patients."	( Impact of SNP-SNP interaction among ABCB1, ARRB2, DRD1 and OPRD1 on methadone dosage requirement in Han Chinese patients. Feng, X; Hu, P; Li, X; Liu, Z; Luo, R; Luo, X; Luo, Z; Qin, S, 2017)	0.89
" An as-treated analysis included a total of 179 participants-128 who were, and 51 who were not, dosed with methadone the day before they were released from the RIDOC."	( A randomized, open label trial of methadone continuation versus forced withdrawal in a combined US prison and jail: Findings at 12 months post-release. Brinkley-Rubinstein, L; Dauria, E; Larney, S; Macmadu, A; McKenzie, M; Rich, J; Zaller, N, 2018)	0.97
"8), lower OAT dosage (aOR = 1."	( Concurrent drug injection during opioid agonist treatment among people who inject drugs in Ukraine. Altice, FL; Dvoriak, S; Filippovich, S; Madden, L; Makarenko, I; Marcus, R; Mazhnaya, A; Pykalo, I, 2018)	0.48
" Methadone and its metabolites were proven to be detectable and quantifiable in skeletal tissue of chronically dosed rats using a fast and easy methanol extraction."	( Distribution of Methadone and Metabolites in Skeletal Tissue. Cuypers, E; Somers, T; Vandenbosch, M, 2018)	1.74
" MMRs provide an objective tool to more efficiently improve the safety and efficacy of methadone dosing perinatally."	( The Use of Serum Methadone/Metabolite Ratios to Monitor Changing Perinatal Pharmacokinetics. Fassbender, C; Graas, J; Leamon, MH; McCarthy, JJ; Vasti, EJ; Ward, C, )	0.69
" Most studies to date have been conducted among heroin users, in controlled settings, and using similar strict dosing schedules (i."	( The OPTIMA study, buprenorphine/naloxone and methadone models of care for the treatment of prescription opioid use disorder: Study design and rationale. Ahamad, K; Bruneau, J; Fischer, B; Jutras-Aswad, D; Le Foll, B; Lim, R; Socias, ME; Wild, TC; Wood, E, 2018)	0.74
" SCI participants received standard methadone dosing and adaptive counseling."	( Treatment initiation strategies for syringe exchange referrals to methadone maintenance: A randomized clinical trial. Brooner, RK; Kidorf, M; Leoutsakos, JM; Peirce, J, 2018)	0.99
" Careful consideration must be given to dosing methadone in both opioid-naïve and opioid-tolerant patients, with vigilant monitoring for therapeutic effectiveness and potential toxicity until the patient achieves steady state."	( Methadone: Maximizing Safety and Efficacy for Pain Control in Patients with Cancer. Costantino, RC; McPherson, AL; McPherson, ML, 2018)	2.18
" In major inpatient surgery, intraoperative single-dose methadone produces better analgesia and reduces opioid use compared with conventional repeated dosing of short-duration opioids."	( Intraoperative Methadone in Same-Day Ambulatory Surgery: A Randomized, Double-Blinded, Dose-Finding Pilot Study. Blood, J; Brunt, LM; Deych, E; Kharasch, ED; Komen, H, 2019)	1.11
"15 mg/kg ideal body weight) or conventional as-needed dosing of short-duration opioids (eg, fentanyl, hydromorphone; controls)."	( Intraoperative Methadone in Same-Day Ambulatory Surgery: A Randomized, Double-Blinded, Dose-Finding Pilot Study. Blood, J; Brunt, LM; Deych, E; Kharasch, ED; Komen, H, 2019)	0.87
" The primary outcome was continuous retention in treatment as measured by opioid agonist dosing records between patients with clinic (onsite) pharmacy dosing versus community (offsite) pharmacy dosing."	( Improved treatment-retention for patients receiving methadone dosing within the clinic providing physician and other health services (onsite) versus dosing at community (offsite) pharmacies. Eibl, JK; Gauthier, G; Marsh, DC, 2018)	0.73
"The results of this study suggest that clinic (onsite) pharmacy methadone dosing results in a greater likelihood of retention in MMT compared to community (offsite) pharmacy dosing."	( Improved treatment-retention for patients receiving methadone dosing within the clinic providing physician and other health services (onsite) versus dosing at community (offsite) pharmacies. Eibl, JK; Gauthier, G; Marsh, DC, 2018)	0.97
" The difference in opioid requirements between the REMI and MET group was related to intraoperative dosing (0."	( Analgesic effects of methadone and magnesium following posterior spinal fusion for idiopathic scoliosis in adolescents: a randomized controlled trial. Barry, N; Beebe, AC; Bhalla, T; Gill, L; Klamar, J; Martin, DP; Rice, J; Samora, WP; Thung, A; Tobias, JD; Tumin, D; Veneziano, G, 2018)	0.8
"With the dosing regimens in the current study, the only benefit noted with methadone was a decrease in perioperative opioid requirements."	( Analgesic effects of methadone and magnesium following posterior spinal fusion for idiopathic scoliosis in adolescents: a randomized controlled trial. Barry, N; Beebe, AC; Bhalla, T; Gill, L; Klamar, J; Martin, DP; Rice, J; Samora, WP; Thung, A; Tobias, JD; Tumin, D; Veneziano, G, 2018)	1.03
" Both SNP-based and gene-based approaches were used, and we tested also the interaction of the top SNP with methadone dosage to predict the QTc length."	( QT length during methadone maintenance treatment: gene × dose interaction. Bellivier, F; Bloch, V; Laplanche, JL; Lepine, JP; Marees, AT; Marie-Claire, C; Mouly, S; Naccache, F; Prince, N; Vorspan, F; Zerdazi, EH, 2019)	1.07
" Data collected included demographic data, laboratory tests, antiretroviral treatment history, methadone dosing and drug abstinence."	( Risk factors for kidney disease among HIV-1 positive persons in the methadone program. Firląg-Burkacka, E; Grycner, E; Horban, A; Kowalska, JD; Matłosz, B; Pietraszkiewicz, E, 2019)	0.97
"008), dosage of methadone (HR=0."	( Three-year retention in methadone opioid agonist treatment: A survival analysis of clients by dose, area deprivation, and availability of alcohol and cannabis outlets. Amiri, S; Amram, O; Hirchak, K; Lutz, R; McDonell, MG; McPherson, SM; Roll, JM, 2018)	1.13
"The findings of this study showed age and methadone dosage were protective factors and area deprivation and years on treatment were risk factors for treatment retention."	( Three-year retention in methadone opioid agonist treatment: A survival analysis of clients by dose, area deprivation, and availability of alcohol and cannabis outlets. Amiri, S; Amram, O; Hirchak, K; Lutz, R; McDonell, MG; McPherson, SM; Roll, JM, 2018)	1.05
" Information on demographics, dosing of methadone, and the use of electrocardiograms (ECGs) was collected."	( Attitudes, Beliefs, and Practices of Pediatric Palliative Care Physicians Regarding the Use of Methadone in Children With Advanced Cancer. Bruera, E; Liu, D; Madden, K, 2019)	1
" Considerable evidence documents the treatment effectiveness of MMT and, in turn, the importance of adequate dosing to MMT's effectiveness."	( Evidence-based treatment for opioid use disorders: A national study of methadone dose levels, 2011-2017. D'Aunno, T; Park, SE; Pollack, HA, 2019)	0.75
"We recruited 3,620 patients in 27 addiction units in Italy and collected data on the self-reported rate of intravenous injection of methadone (MET), buprenorphine (BUP), BUP-naloxone (NLX), OMT dosage and type, experience of and reason for misuse, concurrent intravenous benzodiazepine misuse, pattern of -misuse in relation to admission to the addiction unit and ER -admissions because of misuse."	( Intravenous Misuse of Methadone, Buprenorphine and Buprenorphine-Naloxone in Patients Under Opioid Maintenance Treatment: A Cross-Sectional Multicentre Study. Cibin, M; Lugoboni, F; Tamburin, S; Zamboni, L, 2019)	1.03
" OMT dosage was lower than the recommended maintenance dosage."	( Intravenous Misuse of Methadone, Buprenorphine and Buprenorphine-Naloxone in Patients Under Opioid Maintenance Treatment: A Cross-Sectional Multicentre Study. Cibin, M; Lugoboni, F; Tamburin, S; Zamboni, L, 2019)	0.83
"Our primary aims were to assess current practices in withdrawal management in the perinatal period in patients admitted to an antepartum unit at a tertiary care setting with comorbid opioid and sedative-hypnotic use disorders; specifically, to identify patterns of withdrawal management, including the type of withdrawal protocol utilized, the total dosage of benzodiazepine used during that protocol, to assess patient variables associated with higher dosing, and to analyze neonatal outcomes."	( Benzodiazepine withdrawal in pregnant women with opioid use disorders: An observational study of current clinical practices at a tertiary obstetrical hospital. Gopalan, P; Moses-Kolko, E; Shenai, N; Smith, E; Valpey, R, )	0.13
" They were randomized to receive either OT or methadone with an allocation ratio of 1:1 using a patient-centered flexible dosing strategy."	( Comparing opium tincture and methadone for medication-assisted treatment of patients with opioid use disorder: Protocol for a multicenter parallel group noninferiority double-blind randomized controlled trial. Akhondzadeh, S; Choi, F; Gholami, A; Givaki, R; Goudarzi, N; Jang, K; Javidanbardan, S; Jazani, M; Kazemi, A; Krausz, M; Markazi Moghaddam, N; Moazen-Zadeh, E; Mohammadian, F; Nikoo, M; Nikoo, N; Schutz, C; Tavakoli, S; Vogel, M, 2019)	1.06
"Utilizing divided dosing intervals and regular monitoring for toxicity, the patient received a cumulative methadone dose of 130 mg total within the first 48 hours of admission with continuation of a similar dose subsequently."	( Initiation and Rapid Titration of Methadone in an Acute Care Setting for the Treatment of Opioid Use Disorder: A Case Report. Bach, P; Colizza, K; Hemmons, P; Nolan, S, )	0.62
"A dramatic increase in newborn infants with neonatal abstinence syndrome has been observed and these neonates are frequently treated with complex methadone dosing schemes to control their withdrawal symptoms."	( Methadone dosing strategies in preterm neonates can be simplified. Bordbar, A; Kalani, M; Koch, G; Pfister, M; Samiee-Zafarghandy, S; van den Anker, J; van Donge, T, 2019)	2.16
" Model-based simulations were performed to identify a simplified dosing strategy to reach and maintain target methadone exposure."	( Methadone dosing strategies in preterm neonates can be simplified. Bordbar, A; Kalani, M; Koch, G; Pfister, M; Samiee-Zafarghandy, S; van den Anker, J; van Donge, T, 2019)	2.17
" Preterm neonates reached target exposure after 48 hours with currently used dosing schedules."	( Methadone dosing strategies in preterm neonates can be simplified. Bordbar, A; Kalani, M; Koch, G; Pfister, M; Samiee-Zafarghandy, S; van den Anker, J; van Donge, T, 2019)	1.96
" Simulations that account for developmental PK changes indicate a shorter methadone dosing strategy can maintain target exposure to control withdrawal symptoms."	( Methadone dosing strategies in preterm neonates can be simplified. Bordbar, A; Kalani, M; Koch, G; Pfister, M; Samiee-Zafarghandy, S; van den Anker, J; van Donge, T, 2019)	2.19
" An overall dose-response effect was observed, with higher doses resulting in larger QTcF (QT interval corrected using Fridericia formula) changes from baseline, but none of the changes were considered clinically significant by the investigators."	( Characterization of the Safety and Pharmacokinetic Profile of D-Methadone, a Novel N-Methyl-D-Aspartate Receptor Antagonist in Healthy, Opioid-Naive Subjects: Results of Two Phase 1 Studies. Bernstein, G; Davis, K; Inturrisi, C; Manfredi, PL; McDonnell, M; Mills, C; Oldenhof, J; Vitolo, OV; Wang, L, )	0.37
"Following coadministration with FTR, dose-normalized MET (R-, S- and total) exposures (maximum concentration in plasma, area under the plasma concentration-time curve over the dosing interval and concentration in plasma at 24 hours) increased 9-15% and BUP and norBUP exposures increased 24-39%."	( Methadone and buprenorphine pharmacokinetics and pharmacodynamics when coadministered with fostemsavir to opioid-dependent, human immunodeficiency virus seronegative participants. Ackerman, P; Chang, M; Llamoso, C; Lubin, S; Magee, M; Moore, K; Myers, E; Sevinsky, H, 2019)	1.96
"Opioid agonist treatment is considered important in preventing acquisition of hepatitis C virus (HCV) among people who inject drugs; however, the role of dosage in opioid agonist treatment is unclear."	( Opioid agonist treatment dosage and patient-perceived dosage adequacy, and risk of hepatitis C infection among people who inject drugs. Artenie, AA; Bruneau, J; Gauvin, L; Høj, S; Jacka, B; Jutras-Aswad, D; Minoyan, N; Roy, É; Zang, G, 2019)	0.51
" At 6-month, then 3-month intervals, participants were tested for HCV antibodies or RNA, and completed an interviewer-administered behavioural questionnaire, reporting the following: current exposure to opioid agonist treatment (yes/no), prescribed dosage either high (methadone ≥ 60 mg/d or buprenorphine ≥ 16 mg/d) or low, and perceived dosage adequacy (adequate/inadequate)."	( Opioid agonist treatment dosage and patient-perceived dosage adequacy, and risk of hepatitis C infection among people who inject drugs. Artenie, AA; Bruneau, J; Gauvin, L; Høj, S; Jacka, B; Jutras-Aswad, D; Minoyan, N; Roy, É; Zang, G, 2019)	0.69
"Risk of HCV infection varies considerably according to dosage of opioid agonist treatment and patient-perceived adequacy, with associations indicating both protective and harmful effects relative to no exposure to opioid agonist treatment."	( Opioid agonist treatment dosage and patient-perceived dosage adequacy, and risk of hepatitis C infection among people who inject drugs. Artenie, AA; Bruneau, J; Gauvin, L; Høj, S; Jacka, B; Jutras-Aswad, D; Minoyan, N; Roy, É; Zang, G, 2019)	0.51
" Supervised dosage and other control measures are important provisions in the prevention of drug diversion and non-prescribed use among people not undergoing OST."	( Non-prescribed use of methadone and buprenorphine prior to opioid substitution treatment: lifetime prevalence, motives, and drug sources among people with opioid dependence in five Swedish cities. Johnson, B; Richert, T, 2019)	0.83
" For doravirine and methadone pharmacokinetic analysis, blood samples were collected before dosing through 24 hours after dosing."	( Evaluation of the Pharmacokinetic Interaction Between Doravirine and Methadone. Bouhajib, M; Fan, L; Iwamoto, M; Khalilieh, S; Sanchez, RI; Searle, S; Vaynshteyn, K; Yee, KL, 2020)	1.12
" The lack of reliable dosing ratios, substantial interindividual variability in methadone pharmacodynamics, the potential for extensive drug interactions, and the high potency of methadone compared with other opioids all pose significant barriers to the use of this drug in routine practice."	( Preliminary Validation for the "BJR method"-A Possible New Mathematical Approach to Methadone Conversion. Baumrucker, SJ; Hutchinson, L; Trofimovitch, D, )	0.58
" Reduction in methadone dosage and liver supporting therapy was effective in reducing the drowsiness."	( [A Case of Methadone Induced Drowsiness Following Trabectedin Induced Liver Injury]. Higuchi, M; Ishiki, H; Kiuchi, D; Satomi, E; Shimizu, M, 2019)	1.26
" Emergent themes were: (1) general satisfaction with XR-NTX's long-acting antagonist effects and control of cravings; (2) "testing" XR-NTX's blockade with heroin upon reentry was common; (3) early discontinuation of XR-NTX treatment was most common among persons with high self-efficacy and/or heavy exposure to drug use environments and peers; (4) similar satisfaction regarding effects of methadone and buprenorphine maintenance among retained-in-treatment individuals, alongside general dissatisfaction with daily observed dosing requirements and misinformation and stigmas regarding methadone adverse effects; (5) unstable housing, economic insecurity, and exposure to actively using peers were attributed to early termination of treatment and relapse; (6) individual motivation and willpower as central to long-term opioid abstinence and reentry success."	( Perceptions of extended-release naltrexone, methadone, and buprenorphine treatments following release from jail. Badolato, R; Flannery, M; Garment, AR; Giftos, J; Lee, JD; McDonald, RD; Tofighi, B; Velasquez, M; Vittitow, A, 2019)	0.94
" Study durations ranged from 3 to 13 weeks, and memantine dosing ranged from 5 to 60 mg/day."	( Adjunctive memantine for opioid use disorder treatment: A systematic review. Brown, JN; Elias, AM; Pepin, MJ, 2019)	0.51
" Appropriate dosing of methadone for pain management given age, organ dysfunction, and patients who are on methadone maintenance therapy are also key factors."	( Emerging Challenges to the Safe and Effective Use of Methadone for Cancer-Related Pain in Paediatric and Adult Patient Populations. Ajayi, TA; Atayee, RS; Edmonds, KP; Saunders, IM; Willeford, A, 2020)	1.12
" After pairwise tagger analyses, tagger SNP rs204047 showed a significant association with methadone dosage (P = 0."	( Genetic polymorphisms in the opioid receptor delta 1 (OPRD1) gene are associated with methadone dose in methadone maintenance treatment for heroin dependence. Chen, ACH; Chung, RH; Fang, CP; Hsu, YT; Kuo, HW; Liu, SC; Liu, TH; Liu, YL; Tsou, HH; Wang, SC, 2020)	1
" There are protocols designed to minimize withdrawal; however, these can be time-consuming or infeasible due to formulation and dosage availability of buprenorphine."	( Transition From Methadone to Buprenorphine Using a Short-acting Agonist Bridge in the Inpatient Setting: A Case Study. Callan, J; Pytell, J; Rastegar, DA; Ross, J, )	0.48
" The data suggested underdosing in the URM category, as well as evidence of excessive dosing in IM and USM categories."	( The Use of the Methadone/Metabolite Ratio (MMR) to Identify an Individual Metabolic Phenotype and Assess Risks of Poor Response and Adverse Effects: Towards Scientific Methadone Dosing. Fassbender, C; Graas, J; Leamon, MH; McCarthy, JJ; Vasti, EJ; Ward, C, )	0.48
" Further studies are warranted to explore the optimal dosing strategy for buprenorphine to consistently maintain reversal of respiratory depression but not precipitate withdrawal."	( Buprenorphine to reverse respiratory depression from methadone overdose in opioid-dependent patients: a prospective randomized trial. Buckley, NA; Hassanian-Moghaddam, H; Zamani, N, 2020)	0.81
" The median dosage when side effects began to occur was 15."	( Safety aspects of opioid-naïve patients with high-grade glioma treated with D,L-Methadone: an observational case series. Bettag, C; Rohde, V; Schatlo, B; von der Brelie, C, 2021)	0.85
" Understanding these pharmacologically driven patterns then guides the judicious choice of drug and dosing schedule and the proactive risk management that is crucial to minimising the risk of death in treatment."	( Impact of Pharmacological Treatments for Opioid Use Disorder on Mortality. Hulse, G; Joyce, D; Kelty, E; Preen, DB, 2020)	0.56
" Several factors at the individual, interpersonal, and institutional levels, such as concurrent substance use, MOUD adherence, family conflict, and MOUD dosage and flexibility, appeared to have roles in MOUD retention among adolescents and young adults."	( Adherence to and Retention in Medications for Opioid Use Disorder Among Adolescents and Young Adults. Altice, FL; Bromberg, DJ; Nyhan, K; Refsland, BM; Stanojlović, M; Viera, A; Whittaker, S, 2020)	0.56
" The aims of this review were to summarize eligibility criteria for entry to OAT, doses in routine clinical practice, access to and eligibility for unsupervised dosing and urine drug screening practices in OAT programs globally."	( Global opioid agonist treatment: a review of clinical practices by country. Ali, R; Bruneau, J; Degenhardt, L; Fiellin, DA; Hickman, M; Jin, H; Larney, S; Marshall, BDL; Strang, J, 2020)	0.56
" Access to unsupervised dosing under some conditions was reported in 18 of 27 countries."	( Global opioid agonist treatment: a review of clinical practices by country. Ali, R; Bruneau, J; Degenhardt, L; Fiellin, DA; Hickman, M; Jin, H; Larney, S; Marshall, BDL; Strang, J, 2020)	0.56
" Although the principal methadone metabolizing enzyme remains controversial, our results suggest that sex, CYP2B6 genotype, and BMI should be incorporated into multivariate models to create methadone dosing algorithms."	( Toward precision prescribing for methadone: Determinants of methadone deposition. Brown, LS; Chakan, LM; Dharia, A; Ding, Y; Kharasch, ED; Markatou, M; McLeod, A; Morse, GD; Talal, AH; Venuto, CS, 2020)	1.15
" Furthermore, we found that the dosage of the OAT was significantly associated with the NMR level."	( Pregnant Smokers Receiving Opioid Agonist Therapy Have an Elevated Nicotine Metabolite Ratio: A Replication Study. Hand, D; Kranzler, HR; Lynch, KG; Oncken, C; Schnoll, R; Tyndale, RF; Washio, Y; Zindel, LR, 2020)	0.56
" Use of the developed PBK model to convert concentration-response curves for the effect of methadone on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) in the so-called multi electrode array (MEA) assay resulted in predictions for in vivo dose-response curves for methadone-induced cardiotoxicity that matched the available in vivo data."	( Integrating in vitro data and physiologically based kinetic modeling-facilitated reverse dosimetry to predict human cardiotoxicity of methadone. Bouwmeester, H; Rietjens, IMCM; Shi, M; Strikwold, M, 2020)	0.98
" Although dosing levels for BMT did not influence retention, increasing dosages for MMT were significantly associated with higher retention rates at 1 (90, 96, 99%), 12 (59, 78, 91%) and 36 (34, 59, 79%) months, respectively."	( The real-world impact of dosing of methadone and buprenorphine in retention on opioid agonist therapies in Ukraine. Altice, FL; Bojko, MJ; Dvoriak, S; Farnum, SO; Islam, Z; Madden, L; Makarenko, I; Marcus, R; Mazhnaya, A; Prokhorova, T; Rozanova, J, 2021)	0.9
"To perform a quantitative trait locus association for identifying genetic variants for MMT dosage that underlie heroin addiction and methadone metabolism and then integrate several genotypic and phenotypic factors are potential predictors for clinically optimal MMT dose for personalized prescription."	( Precision therapeutic opioid dosing implications from genetic biomarkers and craving score. Chang, HW; Ho, WC; Huang, CL; Wang, RY, 2020)	0.76
" On the fourteenth day of SROM treatment patients switched from racemic methadone took an average dosage of 922."	( Switching opioid-dependent patients in substitution treatment from racemic methadone, levomethadone and buprenorphine to slow-release oral morphine: Analysis of the switching process in routine care. Baschirotto, C; Kuhn, S; Lehmann, K; Reimer, J; Verthein, U, 2020)	1.02
"Primary: 1) Treatment retention; 2) sustained remission (defined as 3 consecutive negative screens); 3) return to use; 4) methadone dosage required; and 5) number of days to achieve remission."	( One year of methadone maintenance treatment in a fentanyl endemic area: Safety, repeated exposure, retention, and remission. Carroll, JJ; Green, TC; Rich, JD; Stone, AC, 2020)	1.14
"MR for CIBP may result in reduction in pain intensity, when other opioids are ineffective or intolerable, with patients requiring reduced overall dosing of their long-acting opioid and frequency of breakthrough opioid use."	( The role of methadone in cancer-induced bone pain: a retrospective cohort study. Al-Rubaie, Z; Key, S; Kwok, J; Michael, N; Sulistio, M; Wojnar, R, 2021)	1
" Pregnant women (and parents with children) were forced to negotiate dosing in dangerous conditions."	( Changing Outdated Methadone Regulations That Harm Pregnant Patients. Jones, HE; McCarthy, JJ; Rudolf, VP; Terplan, M; von Klimo, MC, 2021)	0.96
" Standard procedures for the acquisition of methadone, of containers for personalized dosing in Centres for the Comprehensive Care of Drug Addiction  Patients, and transport routes were designed and contracted out through public  tender in compliance with the Public Administration Contract Law."	( Centralization of the methadone maintenance plan in a hospital pharmacy department in the Community of Madrid. Aguilar-Ros, A; Álvaro-Alonso, EA; Escobar-Rodríguez, I; Tejedor-Prado, P, 2020)	1.13
" An individualized approach to dosage and route should be considered based on specific clinical circumstances."	( Methadone for Cancer Pain in Pediatric End-of-Life Care. Anghelescu, DL; Habashy, C; Hall, EA; Sauer, HE, 2021)	2.06
" Methadone dosage was significant at a 6-month follow-up."	( Pay for Performance and Treatment Outcome in Agonist Treatment for Opioid Use Disorder. Levit, A; Loscalzo, E; Sterling, RC; Weinstein, SP, 2021)	1.53
"P4P and methadone dosage may have some benefit to individuals in OAT in attaining short-term abstinence from opioids."	( Pay for Performance and Treatment Outcome in Agonist Treatment for Opioid Use Disorder. Levit, A; Loscalzo, E; Sterling, RC; Weinstein, SP, 2021)	1.06
" Currently, the morphine dosing strategies are empiric, not optimal and associated with longer hospital stay."	( Model-Based Approach to Improve Clinical Outcomes in Neonates With Opioid Withdrawal Syndrome Using Real-World Data. Aduroja, O; Biggs, JM; El-Metwally, D; Gopalakrishnan, M; Wijekoon, N, 2021)	0.62
"On March 16, 2020, Ukraine's Ministry of Health issued nonspecific interim guidance to continue enrolling patients in opioid agonist therapies (OAT) and transition existing patients to take-home dosing to reduce community COVID-19 transmission."	( Rapid transitional response to the COVID-19 pandemic by opioid agonist treatment programs in Ukraine. Altice, FL; Dvoryak, S; Farnum, SO; Filippovych, M; Fomenko, T; Galvez de Leon, SJ; Islam, ZM; Madden, LM; Meteliuk, A; Pykalo, I, 2021)	0.62
" In all analyses, methadone and buprenorphine dosing were evaluated as a continuous variable."	( Delivery dose of methadone, but not buprenorphine, is associated with the risk and severity of neonatal opiate withdrawal syndrome. Bailit, JL; Gibson, KS; Lappen, JR; Stark, S, 2020)	1.23
" These data may inform future prospective studies on methadone dosing in pregnancy."	( Delivery dose of methadone, but not buprenorphine, is associated with the risk and severity of neonatal opiate withdrawal syndrome. Bailit, JL; Gibson, KS; Lappen, JR; Stark, S, 2020)	1.15
" Less than 1% of pillbox alerts were for medication being consumed outside the dosing window and we observed no evidence of actual or attempted methadone diversion."	( Technology-assisted methadone take-home dosing for dispensing methadone to persons with opioid use disorder during the Covid-19 pandemic. Brooner, RK; Dunn, KE; Stoller, KB, 2021)	1.15
" This review discusses the utility of pharmacometric techniques for enhancing precision dosing in infants requiring opioid treatment for NOWS."	( Opioid Treatment for Neonatal Opioid Withdrawal Syndrome: Current Challenges and Future Approaches. Akinbi, H; Butler, D; Emoto, C; Fukuda, T; McPhail, BT; Vinks, AA, 2021)	0.62
" Post-operative methadone dosing was compared to preoperative methadone dosing."	( Perioperative methadone prescribing and association with respiratory depression. Bova, SE; Grant, MC; Jarrell, AS; Kruer, RM; Nesbit, SA, )	0.84
" This study aims to improve clinicians' therapeutic decision-making by identifying the reasons for increasing daily methadone maintenance dosage among deceptive patients."	( Reasons for Increasing Daily Methadone Maintenance Dosage among Deceptive Patients: A Qualitative Study. Kasaeiyan, R; Khosravi, M, )	0.63
"Intraoperative methadone, a long-acting opioid, is increasingly used for postoperative analgesia, although the optimal methadone dosing strategy in children is still unknown."	( A Novel Perioperative Multidose Methadone-Based Multimodal Analgesic Strategy in Children Achieved Safe and Low Analgesic Blood Methadone Levels Enabling Opioid-Sparing Sustained Analgesia With Minimal Adverse Effects. Aruldhas, BW; Fitzgerald, RE; Overholser, BR; Packiasabapathy, S; Quinney, SK; Renschler, JS; Sadhasivam, S; Zang, Y; Zhang, P, 2021)	1.26
" This methadone dosing in a multimodal regimen resulted in lower blood methadone analgesia concentrations than the historically described minimum analgesic concentrations of methadone from an era before multimodal postoperative analgesia without postoperative respiratory depression and prolonged corrected QT (QTc)."	( A Novel Perioperative Multidose Methadone-Based Multimodal Analgesic Strategy in Children Achieved Safe and Low Analgesic Blood Methadone Levels Enabling Opioid-Sparing Sustained Analgesia With Minimal Adverse Effects. Aruldhas, BW; Fitzgerald, RE; Overholser, BR; Packiasabapathy, S; Quinney, SK; Renschler, JS; Sadhasivam, S; Zang, Y; Zhang, P, 2021)	1.39
" Female Sprague-Dawley rats were treated orally with an ascending methadone dosage schedule (5, 10, 15, 20, 25 and 30 mg/kg/day), self-administered in drinking water prior to conception, throughout gestation and lactation."	( Prenatal methadone exposure impairs adolescent cognition and GABAergic neurodevelopment in a novel rat model of maternal methadone treatment. Bird, KM; Lum, JS; Millard, SJ; Newell, KA; Pallimulla, S; Wilkie, J; Wright, IM, 2021)	1.28
"Our study found variation in experiences of take-home dosing by clinic and little diversion of take-home doses."	( Take-home dosing experiences among persons receiving methadone maintenance treatment during COVID-19. Dasgupta, N; Day, E; Figgatt, MC; Salazar, Z; Vincent, L, 2021)	0.87
" Methadone dosage was negatively associated with craving."	( Craving and implicit attitude toward heroin use and their relationships with the levels of heroin dependence and methadone adherence in heroin users. Chung, KS; Connie Yang, YH; Hsu, CY; Ko, CH; Lee, KH; Lin, HC; Pai-Cheng, L; Wang, PW; Wu, HC; Yen, CF, )	1.25
"To assess the pharmacokinetics and opioid effects of methadone after administration of multiple doses by means of 2 dosing regimens of methadone-fluconazole-naltrexone."	( Multiple-dose pharmacokinetics and opioid effects of a novel analgesic with a deterrent to human opioid abuse (methadone-fluconazole-naltrexone) after oral administration in dogs. Cho, P; Fitzgerald, AH; Komp, MS; KuKanich, B; KuKanich, K; Locuson, CW; Rankin, DC, 2021)	1.08
"Dogs were randomly allocated (6 dogs/group) to receive 1 of 2 oral dosing regimens of methadone-fluconazole-naltrexone."	( Multiple-dose pharmacokinetics and opioid effects of a novel analgesic with a deterrent to human opioid abuse (methadone-fluconazole-naltrexone) after oral administration in dogs. Cho, P; Fitzgerald, AH; Komp, MS; KuKanich, B; KuKanich, K; Locuson, CW; Rankin, DC, 2021)	1.06
" Illegal sales and consumption of methadone have a negative impact on the self-administration therapy of opioid addiction, inducing patients to increase their dosage or sell methadone in order to purchase illegal drugs."	( Forensic pathological study of methadone-related deaths in the Genoa (Italy) district: A six-year study. Barranco, R; Bedocchi, D; Bonsignore, A; Drommi, M; Errico, S; Ventura, F, 2021)	1.19
"1 mg · kg-1 · h-1 for next 48 h [both medications dosed at ideal body weight]; methadone/ketamine group)."	( Perioperative Methadone and Ketamine for Postoperative Pain Control in Spinal Surgical Patients: A Randomized, Double-blind, Placebo-controlled Trial. Avram, MJ; Benson, J; Bilimoria, S; Greenberg, SB; Maher, CE; Murphy, GS; Szokol, JW; Teister, K, 2021)	1.21
" Prior studies relied on nonstandard dosing of tablets or films, patches, or buccal formulations, all of which are unavailable in many hospitals."	( Micro-dosing Intravenous Buprenorphine to Rapidly Transition From Full Opioid Agonists. Jablonski, L; Rastegar, DA; Ratner, J; Thakrar, AP, )	0.13
" While some clinicians expressed support for the increased flexibility around dosing and use of telemedicine, others expressed concern about increased risk of medication diversion and overdose."	( Clinician perspectives on methadone service delivery and the use of telemedicine during the COVID-19 pandemic: A qualitative study. Dopp, AR; Hunter, SB; Ober, AJ; Uscher-Pines, L, 2021)	0.92
" High maternal dosing of buprenorphine is associated with lower BW and HC Z-scores but dose effect is not seen with methadone."	( Impact of opioid maintenance treatment during pregnancy on neonatal birth weight and head circumference. Adekola, H; Bruder, A; Kumar, N; Masten, M; Monga, R; Moustafa, ASZ; Parmar, K; Rocha, FG; Sampath, V, 2021)	0.83
" Opioid-related variables as seroprevalence rates, other previous lifetime maintenance program, the daily opioid dosage and the daily alcohol use are the most discriminative variables between both groups."	( Evaluation of functional status among patients undergoing maintenance treatments for opioid use disorders. García-Marchena, N; Martinez Delgado, JM; Ruíz Ruíz, JJ, 2021)	0.62
" Rigorous supervision of daily dosing at opioid maintenance clinics as well as efforts to control the black-market offering methadone are needed to prevent further methadone-related acute poisonings and deaths."	( Trends of acute drug and chemical toxicities in adults and adolescents in Tehran, Iran between 2012 and 2018: a retrospective chart review. Amirabadizadeh, A; Hadeiy, SK; Hassanian-Moghaddam, H; Khoshkar, A; Kolahi, AA; Parhizgar, P; Rezaei, O; Zamani, N, 2022)	0.93
"Despite its availability for more than 70 years, many details concerning methadone remain contentious, such as the dosing equivalents for intravenous and enteral administration."	( Methadone bioavailability and dose conversion implications with intravenous and enteral administration: A scoping review. Craig, WY; Fraser, GL; Kemp, HD; Liu, J; McKelvy, DJ; Nichols, SD; Riker, RR; Smith, KE, 2021)	2.3
"Available evidence suggests the bioavailability of methadone is generally more than 75%, there is limited evidence for the currently recommended 1:2 ratio (intravenous:enteral), and a more appropriate dosing ratio may be 1:1."	( Methadone bioavailability and dose conversion implications with intravenous and enteral administration: A scoping review. Craig, WY; Fraser, GL; Kemp, HD; Liu, J; McKelvy, DJ; Nichols, SD; Riker, RR; Smith, KE, 2021)	2.32
" We used careful diagnostics, simultaneous psychosocial efforts were given, the outcome was continously evalutated and the dosage was administered according to the principle of lowest effective dose."	( [Methadone and buprenorphine maintenance therapy of opioid dependence - 10 years of experience]. Hoffmann, O; Ljungberg, T, 2021)	1.53
" Some systems deviated from evidence-based treatment by limiting OAT dosage to low levels, requiring counseling for participation and requiring detoxification before medication initiation."	( Methadone and buprenorphine treatment in United States jails and prisons: lessons from early adopters. Bandara, S; Barry, CL; Kennedy-Hendricks, A; Merritt, S; Saloner, B, 2021)	2.06
"Opioid treatment programs (OTPs) may provide interim methadone services - up to 120 days of methadone dosing without counseling."	( Interim methadone - Effective but underutilized: A scoping review. Bougatsos, C; Chan, B; Chou, R; Grusing, S; McCarty, D, 2021)	1.31
" We also analyzed state-level data on confirmed accidental opioid-involved deaths to assess if relaxation of take-home dosing restrictions and in-person attendance requirements correlated with increased methadone-involved fatal overdose rates."	( Changes in methadone program practices and fatal methadone overdose rates in Connecticut during COVID-19. Brothers, S; Heimer, R; Viera, A, 2021)	1.2
" OTP providers said restrictions on methadone should be relaxed and increases in take-home dosing as well as telehealth should be continued in non-pandemic situations."	( Changes in methadone program practices and fatal methadone overdose rates in Connecticut during COVID-19. Brothers, S; Heimer, R; Viera, A, 2021)	1.29
" Since relaxing restrictions on methadone treatment has not increased fatal overdoses, we recommend that the reductions in-person dosing and attendance requirements implemented during the COVID-19 pandemic should be continued and made permanent."	( Changes in methadone program practices and fatal methadone overdose rates in Connecticut during COVID-19. Brothers, S; Heimer, R; Viera, A, 2021)	1.29
" Despite this, a paucity of data exist regarding the most appropriate optimal dosing regimens during pregnancy."	( Precision dosing of methadone during pregnancy: A pharmacokinetics virtual clinical trials study. Badhan, RKS; Gittins, R, 2021)	0.94
" This study did so to derive a theoretical optimal dosing regimen during pregnancy, and to identify the impact of Cytochromes P450 (CYP) 2B6 and 2C19 polymorphisms on methadone maternal and fetal pharmacokinetics."	( Precision dosing of methadone during pregnancy: A pharmacokinetics virtual clinical trials study. Badhan, RKS; Gittins, R, 2021)	1.14
" The developed optimal dosing regimen escalated doses to 110 mg by week 5, followed by 10 mg increments every 5 weeks up to a maximum of 180 mg once daily near term."	( Precision dosing of methadone during pregnancy: A pharmacokinetics virtual clinical trials study. Badhan, RKS; Gittins, R, 2021)	0.94
" In the final adjusted models, clients who reported using methamphetamine in the last 30 days experienced a significantly larger increase in take-home dosage (55."	( Changes in methadone take-home dosing before and after COVID-19. Amiri, S; Amram, O; Joudrey, PJ; Lutz, R; Thorn, EL, 2022)	1.11
"These results suggest that the Spokane OTP quickly expanded take-home medication dosing in response to the COVID-19 exemption and broadly expanded take-home dosing among established clients."	( Changes in methadone take-home dosing before and after COVID-19. Amiri, S; Amram, O; Joudrey, PJ; Lutz, R; Thorn, EL, 2022)	1.11
" OT was perceived to produce lower levels of physiological dependence than methadone, but the requirement for twice supervised dosing was restrictive."	( Factors influencing engagement and utilisation of opium tincture-assisted treatment for opioid use disorder: A qualitative study in Tehran, Iran. Bastani, P; Charkhgard, N; Conigrave, KM; Kebriaeezadeh, A; Mirrahimi, B; Narenjiha, H; Noroozi, A; Salehi, M; Vaziri, A, 2022)	0.95
"Relaxation of federal regulations for methadone take-out dosing during the COVID-19 pandemic is unprecedented."	( Did drug use increase following COVID-19 relaxation of methadone take-out regulations? 2020 was a complicated year. Bart, G; Hodges, JS; Rosenthal, R; Wastvedt, S, 2022)	1.24
" In response, this article examines how clinics' take-home dosing policies have affected patients' experiences of treatment and lives in general."	( "It's like 'liquid handcuffs": The effects of take-home dosing policies on Methadone Maintenance Treatment (MMT) patients' lives. Curran, L; Frank, D; Guarino, H; Mateu-Gelabert, P; Perlman, DC; Walters, SM, 2021)	0.85
" The knowledge of these important covariates will aid in the optimal dosing of methadone in children."	( Pharmacokinetic modeling of R and S-Methadone and their metabolites to study the effects of various covariates in post-operative children. Aruldhas, BW; Gao, H; Heathman, MA; Ly, RC; Masters, AR; Overholser, BR; Packiasabapathy, S; Quinney, SK; Sadhasivam, S, 2021)	1.12
" Participants had histories of both heroin and prescription opioid use, and previous OAT including daily dosing of buprenorphine and methadone."	( Tracing the affordances of long-acting injectable depot buprenorphine: A qualitative study of patients' experiences in Australia. Arunogiri, S; Barnett, A; Bathish, R; Dunlop, AJ; Graham, R; Haber, P; Hayes, V; Lintzeris, N; Lubman, DI; Savic, M, 2021)	0.83
" Furthermore, mQTL rs5326 was associated with the susceptibility and effective dosage of MMT for heroin use disorder, and demonstrated allele-specific correlation with the expression of the DRD1 gene in the human caudate."	( Methylation quantitative trait locus rs5326 is associated with susceptibility and effective dosage of methadone maintenance treatment for heroin use disorder. Fan, Y; Gao, K; Ma, T; Xiao, Y; Xu, M; Zhang, J; Zhou, J; Zhu, Y, 2021)	0.84
" The largest hazard ratios for earlier cessation from the deep learning model were observed for treatment factors, including private dosing points (HR=1."	( Using administrative data to predict cessation risk and identify novel predictors among new entrants to opioid agonist treatment. Barbieri, S; Bharat, C; Degenhardt, L; Dobbins, T; Farrell, M; Larney, S, 2021)	0.62
" Participants were on stable methadone dosing for 9 months prior to and following March 2020."	( The impact of relaxation of methadone take-home protocols on treatment outcomes in the COVID-19 era. Amiri, S; Amram, O; Joudrey, PJ; Lutz, R; Panwala, V; Socias, E, 2021)	1.21
" Obtaining an ECG at baseline, following a dosage increase, or after switching an opioid medication, is appropriate in patients taking certain prescribed opioids."	( Effects of opioid receptor agonist and antagonist medications on electrocardiogram changes and presentation of cardiac arrhythmia: review article. Catanzaro, JN; Delisle, BP; Di Biase, L; Elayi, CS; Etaee, F; Komaki, A; Natale, A; Tobin, M; Vuppala, S, 2022)	0.72
"0% for slow-release oral morphine) and half of all episodes that completed induction reached the minimum effective dosage (51."	( Assessing the determinants of completing OAT induction and long-term retention: A population-based study in British Columbia, Canada. Dale, LM; Kurz, M; Min, JE; Nosyk, B, 2022)	0.72
" All MOUD doses were directly observed and abstracted from dosing logs."	( Correlates of days of medication for opioid use disorder exposure among people living with HIV in Northern Vietnam. Bart, G; Blazes, CK; Button, D; Cook, R; Giang, LM; Khuyen, TT; King, C; Korthuis, PT; Kunkel, L; Nguyen, DB; Thuy, DT, 2022)	0.72
" The role of NMDA receptor in the regulatory mechanisms of methadone dosage in heroin dependent patients is so far not clear."	( Association of the D-amino acid oxidase gene with methadone dose in heroin dependent patients under methadone maintenance treatment. Chen, ACH; Chung, RH; Fang, CP; Kuo, HW; Liu, SC; Liu, TH; Liu, YL; Tsou, HH; Wang, SC, 2022)	1.22
" We aimed to assess the immediate effects of the methadone reformulation on missed doses, days off methadone, changes in medication dosing and dispensations of opioids for pain, and hospitalizations and mortality among all people receiving treatment at or near the time of the change."	( The effect of a methadone reformulation on opioid agonist treatment outcomes: A population-based study in British Columbia, Canada, 2013-14. Dale, LM; Hongdilokkul, N; Krebs, E; Min, JE; Nosyk, B; Schnepel, KT; Shigeoka, H, 2022)	1.32
" However, evidence to guide appropriate dosing of pharmacotherapy for the treatment of opioid use disorder, such as methadone, based on self-reported opioid use during pregnancy is limited."	( Does self-reported consumption of heroin correlate with dose of methadone among pregnant people with opioid use disorder? Arlandson, ME; Gonzalez, AM; Patel, A; Premkumar, A, 2022)	1.17
" It is important to evaluate the changes in unsupervised OAT dosing after the release of the Ontario COVID-19 OAT Guidance based on patients' and prescribers' reports."	( Evaluating how has care been affected by the Ontario COVID-19 Opioid Agonist Treatment Guidance: Patients' and prescribers' experiences with changes in unsupervised dosing. Barrass, S; Corace, K; Cragg, S; Hutton, B; Konefal, S; Leece, P; Pana, P; Porath, A; Suschinsky, K; Wyman, J, 2022)	0.72
" Patients (N = 402) and prescribers (N = 100) reported their experiences with changes in unsupervised dosing during the first six months of the pandemic."	( Evaluating how has care been affected by the Ontario COVID-19 Opioid Agonist Treatment Guidance: Patients' and prescribers' experiences with changes in unsupervised dosing. Barrass, S; Corace, K; Cragg, S; Hutton, B; Konefal, S; Leece, P; Pana, P; Porath, A; Suschinsky, K; Wyman, J, 2022)	0.72
"Opioid agonist treatment (OAT) clients frequently bear costs associated with their treatment, including dosing fees."	( Examining the cost and impact of dosing fees among clients in opioid agonist treatment: Results from a cross-sectional survey of Australian treatment clients. Ali, R; Byrne, J; Chen, R; Degenhardt, L; Farrell, M; Larance, B; Nielsen, S; Santo, T; Tran, AD; Zahra, E, 2022)	0.72
" Dosing fees were calculated and expressed as percentage of income, by OAT type."	( Examining the cost and impact of dosing fees among clients in opioid agonist treatment: Results from a cross-sectional survey of Australian treatment clients. Ali, R; Byrne, J; Chen, R; Degenhardt, L; Farrell, M; Larance, B; Nielsen, S; Santo, T; Tran, AD; Zahra, E, 2022)	0.72
"A total of N = 360 participants had ever been in OAT and N = 245 participants currently engaged in OAT reported data on dosing fees, of them 53% (n = 129) reported paying dosing fees."	( Examining the cost and impact of dosing fees among clients in opioid agonist treatment: Results from a cross-sectional survey of Australian treatment clients. Ali, R; Byrne, J; Chen, R; Degenhardt, L; Farrell, M; Larance, B; Nielsen, S; Santo, T; Tran, AD; Zahra, E, 2022)	0.72
"Negative consequences of treatment costs to clients, particularly dosing fees, are evident."	( Examining the cost and impact of dosing fees among clients in opioid agonist treatment: Results from a cross-sectional survey of Australian treatment clients. Ali, R; Byrne, J; Chen, R; Degenhardt, L; Farrell, M; Larance, B; Nielsen, S; Santo, T; Tran, AD; Zahra, E, 2022)	0.72
"Adequate dosing of MOUD leads to improved retention on MOUD."	( Factors associated with retention on medications for opioid use disorder among a cohort of adults seeking treatment in the community. Biondi, BE; Schlossberg, EF; Shaw, A; Springer, SA; Vander Wyk, B, 2022)	0.72
" However, given that changes were small, strategies to improve retention in OAT and ensure equitable access to take-home dosing should continue."	( Impact of the COVID-19 pandemic on the provision of take-home doses of opioid agonist therapy in Ontario, Canada: A population-based time-series analysis. Antoniou, T; Bozinoff, N; Campbell, TJ; Gomes, T; Kitchen, SA; Men, S; Munro, C; Tadrous, M; Werb, D; Wyman, J, 2022)	0.72
"To determine the effective dosage of the combination tiletamine-zolazepam-ketamine-xylazine (TKX), with or without methadone, in dogs."	( Determination of the effective dosage of tiletamine-zolazepam-ketamine-xylazine, with or without methadone, in dogs. Baier, ME; Herrera Becerra, JR; Martins, LGB; Monteiro, ER; Souza, MJ, 2022)	1.15
" These areas include improving uptake of shared decision-making to increase patient autonomy and agency, particularly among those in the earliest stages of recovery during pregnancy; ongoing education around perinatal MOUD safety and efficacy; detangling MOUD and neonatal withdrawal signs from mandated child protective services reporting; and improving gender-responsive and equitable care in substance use disorder treatment programs, including incorporating the utilization of home visiting services for dosing assessments and administration in the early postpartum period."	( "You have to take this medication, but then you get punished for taking it:" lack of agency, choice, and fear of medications to treat opioid use disorder across the perinatal period. Bernstein, J; Gray, JR; Greenfield, SF; Hoeppner, BB; Jones, HE; Kelly, JF; MacMillan, KDL; Muftu, S; Partridge, S; Schiff, DM; Terplan, M; Wilens, TE; Work, EC, 2022)	0.72
" There were no significant differences in NOWS hospital outcomes between groups in adjusted models: transition to scheduled dosing (methadone 31."	( Neonatal Opioid Withdrawal Syndrome: A Comparison of As-Needed Pharmacotherapy. Gupta, M; MacMillan, KDL; Melvin, P; Morrison, TM; Murzycki, J; O'Shea, TF; Rothstein, R; Schiff, DM; Singh, R; Van Vleet, MW; Wachman, EM, 2022)	0.93
" Intensive therapy was of a complex nature, including infusion-detoxification therapy, correction of acid-base state disorders, hypoxic disorders, by using the substrate antihypoxant "Cytoflavin" in a daily dosage of 60 ml, for 15 days, against the background of basic infusion therapy and vasopressor support ."	( [CLINICAL CASE OF ACUTE SEVERE COMBINED POISONING WITH NARCOTIC SUBSTANCES OF DEPENDENT AND PSYCHOSTIMULATING EFFECTS]. Antonova, A; Batotsyrenov, B; Kovalenko, A; Lodyagin, A; Loladze, A; Sinenchenko, A, 2022)	0.72
" Children with obesity are commonly prescribed the opioids fentanyl and methadone, and accurate dosing is critical to reducing the risk of serious adverse events associated with overexposure."	( Use of physiologically-based pharmacokinetic modeling to inform dosing of the opioid analgesics fentanyl and methadone in children with obesity. Al-Uzri, A; Atz, AM; Carreño, FO; Delmore, P; Edginton, AN; Ford, JL; Gerhart, JG; Gonzalez, D; Muller, WJ; Perrin, EM; Watt, KM, 2022)	1.17
" We assessed the effects of COVID-19-related changes on take-home methadone dosing in two OTPs serving five rural Oregon counties."	( Treatment retention, return to use, and recovery support following COVID-19 relaxation of methadone take-home dosing in two rural opioid treatment programs: A mixed methods analysis. Cook, R; Foot, C; Hoffman, KA; Korthuis, PT; Levander, XA; McCarty, D; McIlveen, JW; Terashima, JP, 2022)	1.18
" Semi-structured qualitative interviews (n = 32) explored patient reactions to increased take-home dosing and reduced clinic visits to provide context for quantitative findings."	( Treatment retention, return to use, and recovery support following COVID-19 relaxation of methadone take-home dosing in two rural opioid treatment programs: A mixed methods analysis. Cook, R; Foot, C; Hoffman, KA; Korthuis, PT; Levander, XA; McCarty, D; McIlveen, JW; Terashima, JP, 2022)	0.94
" Each percentage point increase in take-home dosing above what would be expected without COVID-19 policy changes was negatively associated with the percent of UDT positive for opioids (B = -0."	( Treatment retention, return to use, and recovery support following COVID-19 relaxation of methadone take-home dosing in two rural opioid treatment programs: A mixed methods analysis. Cook, R; Foot, C; Hoffman, KA; Korthuis, PT; Levander, XA; McCarty, D; McIlveen, JW; Terashima, JP, 2022)	0.94
" Chemical specific adjustment factors were defined and used to derive dose-response curves for the sensitive individuals."	( In vitro-in silico-based prediction of inter-individual and inter-ethnic variations in the dose-dependent cardiotoxicity of R- and S-methadone in humans. Bouwmeester, H; Dong, Y; Rietjens, IMCM; Shi, M; Strikwold, M, 2022)	0.93
"Flexible take-home dosing buprenorphine/naloxone or supervised methadone models of care for 24 weeks."	( Impact of fentanyl use on initiation and discontinuation of methadone and buprenorphine/naloxone among people with prescription-type opioid use disorder: secondary analysis of a Canadian treatment trial. Bozinoff, N; Bruneau, J; Choi, JC; Hassan, A; Jutras-Aswad, D; Le Foll, B; Lim, R; Mok, WY; Rehm, J; Socias, ME; Wild, TC; Wood, E, 2022)	1.2
" This study aims to describe tolerability and completion of LDI using intravenous (IV) buprenorphine and to define dosing protocols in a cohort of patients hospitalized in an urban academic hospital."	( Development of an intravenous low-dose buprenorphine initiation protocol. Bodnar, AR; Jablonski, LA; Stewart, RW, 2022)	0.72
" Cases were categorized based on adherence to a dosing strategy and LDI indication, including OUD and acute pain, non-prescribed fentanyl exposure, and transition from methadone."	( Development of an intravenous low-dose buprenorphine initiation protocol. Bodnar, AR; Jablonski, LA; Stewart, RW, 2022)	0.92
"4) for the "rapid," "moderate," and "slow" dosing strategies, respectively."	( Development of an intravenous low-dose buprenorphine initiation protocol. Bodnar, AR; Jablonski, LA; Stewart, RW, 2022)	0.72
" Dosing protocols allowed for rapid transition to sublingual buprenorphine."	( Development of an intravenous low-dose buprenorphine initiation protocol. Bodnar, AR; Jablonski, LA; Stewart, RW, 2022)	0.72
" The patient was also taking pregabalin which was initially started at dosing of 50 mg taken orally three times a day."	( Lucid Dreams Associated with Pregabalin: Implications for Clinical Practice. Chang, YD; Craig, DS; Guastella, AM; Haas, MF; Latchman, J, 2022)	0.72
" Once young people initiated OAT, staying on it was difficult and complicated by daily witnessed dosing requirements and strict rules around repeated missed doses, especially for those receiving methadone."	( Navigating Opioid Agonist Therapy among Young People who use Illicit Opioids in Vancouver, Canada. Buxton, JA; DeBeck, K; Fast, D; Joe, R; Kwa, Y; Pilarinos, A; Thulien, M, 2022)	0.91
" A need exists to adapt methadone dosing from opioid treatment programs (OTPs) in this era."	( Adapting methadone inductions to the fentanyl era. Buresh, M; Nahvi, S; Steiger, S; Weinstein, ZM, 2022)	1.45
" The effects of buprenorphine on sleep-like measures resulted in a biphasic dose-response function, with the highest doses not disrupting actigraphy-based sleep."	( Effects of methadone, buprenorphine, and naltrexone on actigraphy-based sleep-like parameters in male rhesus monkeys. Berro, LF; Freeman, KB; Rowlett, JK; Talley, JT; Zamarripa, CA, 2022)	1.11
"Participants were assigned to either OT (102) or methadone (102) using a patient-centred flexible dosing strategy."	( Opium tincture versus methadone for opioid agonist treatment: a randomized controlled trial. Akhondzadeh, S; Choi, F; Gholami, A; Givaki, R; Jang, K; Javidanbardan, S; Jazani, M; Kazemi, A; Kianpoor, K; Krausz, M; Moazen-Zadeh, E; Moghaddam, NM; Mohammadian, F; Nikoo, M; Nikoo, N; Schütz, C; Tavakoli, S; Vogel, M; Wong, JSH, 2023)	1.48
" OPRM1 and COMT are receiving increasing attention and have implications for all opioids, with changes in opioid dosage requirements observed but they have not yet been studied widely enough to be considered clinically actionable."	( The Role of Pharmacogenomics in Opioid Prescribing. Philip, J; Rubio, J; Somogyi, AA; Wong, AK, 2022)	0.72
"We analyzed data from a multicentric, pragmatic, 24-week open-label randomized controlled trial conducted in participants with POUD (N = 272) who were randomly assigned to BUP/NX model of care with flexible take-home dosing (n = 138) or the standard model of care with closely supervised methadone (n = 134)."	( Buprenorphine/naloxone and methadone effectiveness for reducing craving in individuals with prescription opioid use disorder: Exploratory results from an open-label, pragmatic randomized controlled trial. Bastien, G; Brissette, S; Bruneau, J; Eugenia Socias, M; Foll, BL; Jutras-Aswad, D; Ledjiar, O; Lim, R; Marsan, S; McAnulty, C; Talbot, A, 2022)	1.19
"Compared to the standard methadone model of care, flexible take-home dosing of BUP/NX was associated with lower craving in individuals with POUD."	( Buprenorphine/naloxone and methadone effectiveness for reducing craving in individuals with prescription opioid use disorder: Exploratory results from an open-label, pragmatic randomized controlled trial. Bastien, G; Brissette, S; Bruneau, J; Eugenia Socias, M; Foll, BL; Jutras-Aswad, D; Ledjiar, O; Lim, R; Marsan, S; McAnulty, C; Talbot, A, 2022)	1.32
" Participants receive inpatient rotation to either BuNa or methadone with a flexible dosing regimen."	( Buprenorphine/naloxone versus methadone opioid rotation in patients with prescription opioid use disorder and chronic pain: study protocol for a randomized controlled trial. Dahan, A; Ellerbroek, H; Kramers, C; Schellekens, AFA; Timmerman, H; van den Heuvel, SAS, 2022)	1.25
" We estimated the extent to which different dosing strategies would affect risk of relapse over 12 weeks of treatment, separately for BUP-NX and methadone."	( Buprenorphine & methadone dosing strategies to reduce risk of relapse in the treatment of opioid use disorder. Díaz, I; Fishman, M; Goodwin, ATS; Luo, S; Nunes, EV; Rotrosen, J; Rudolph, KE; Shulman, M; Williams, NT, 2022)	1.27
" We examined four dosing strategies: 1) increasing dose in response to participant-specific opioid use, 2) increasing dose weekly until some minimum dose (16 mg BUP, 100 mg methadone) was reached, 3) increasing dose weekly until some minimum and increasing dose in response to opioid use thereafter (referred to as the "hybrid strategy"), and 4) keeping dose constant after the first 2 weeks of treatment."	( Buprenorphine & methadone dosing strategies to reduce risk of relapse in the treatment of opioid use disorder. Díaz, I; Fishman, M; Goodwin, ATS; Luo, S; Nunes, EV; Rotrosen, J; Rudolph, KE; Shulman, M; Williams, NT, 2022)	1.26
" Data collected included baseline demographics, history of illicit drug use, temporal trend in methadone dosage modulation, and co-use of illicit drugs during the MMT."	( Methadone Maintenance Treatment for Opioid Dependents: a Retrospective Study. Abdul Rashid, Q; Jamaluddin, R; Khalid, K; Mohammad Yusoff, MZA; Ooi, YT, 2022)	2.38
" Opioid agonist treatment (OAT) with oral methadone or daily sublingual buprenorphine hydrochloride, either administered separately or in combination with naloxone hydrochloride (SL-BPN, SL-BPN/NX), is supervised by a healthcare professional experienced in treating opioid use disorder to ensure proper dosing and prevent misuse."	( Administration and patient-incurred costs associated with opioid agonist treatment in Norway. Danø, A; Gibbons, C; Jensen, R; Pedersen, MH, 2022)	0.99
"Novel buprenorphine dosing strategies have emerged with an aim to transition patients from opioid agonists to buprenorphine without prerequisite opioid withdrawal."	( Factors that distinguish opioid withdrawal during induction with buprenorphine microdosing: a configurational analysis. D M, S; E J, M; K K, A, 2022)	0.72
" However, requirements for observing methadone dosing can impose barriers to patients and increase risk for respiratory illness transmission (e."	( Acceptability, feasibility, and outcomes of a clinical pilot program for video observation of methadone take-home dosing during the COVID-19 pandemic. Blalock, KL; Darnton, J; Grekin, P; Hallgren, KA; Michaels, A; Saxon, AJ; Soth, S; Tsui, JI; Woolworth, S, 2022)	1.21
"Between April and August 2020, a clinical pilot program of video observation of methadone take-home dosing via smartphone was conducted within a multisite OTP agency."	( Acceptability, feasibility, and outcomes of a clinical pilot program for video observation of methadone take-home dosing during the COVID-19 pandemic. Blalock, KL; Darnton, J; Grekin, P; Hallgren, KA; Michaels, A; Saxon, AJ; Soth, S; Tsui, JI; Woolworth, S, 2022)	1.17
" Full pilot participants had more days with observed dosing over a 60-day period than matched controls (mean = 53."	( Acceptability, feasibility, and outcomes of a clinical pilot program for video observation of methadone take-home dosing during the COVID-19 pandemic. Blalock, KL; Darnton, J; Grekin, P; Hallgren, KA; Michaels, A; Saxon, AJ; Soth, S; Tsui, JI; Woolworth, S, 2022)	0.94
"Video observation of methadone take-home dosing implemented during the COVID-19 pandemic was feasible."	( Acceptability, feasibility, and outcomes of a clinical pilot program for video observation of methadone take-home dosing during the COVID-19 pandemic. Blalock, KL; Darnton, J; Grekin, P; Hallgren, KA; Michaels, A; Saxon, AJ; Soth, S; Tsui, JI; Woolworth, S, 2022)	1.26
" There are many challenges in conducting studies in advanced cancer with significant attrition and small sample sizes, however it is hoped that the results of our study will contribute to the evidence base and allow for continued development of gene-drug dosing guidelines for clinicians."	( Association of KCNJ6 rs2070995 and methadone response for pain management in advanced cancer at end-of-life. Albury, CL; George, R; Good, P; Griffiths, LR; Hardy, J; Haupt, LM; Haywood, A; Ozberk, D; Sutherland, HG; Yu, C; Zunk, M, 2022)	1
" Specific areas of focus elaborated by the authors include: better characterization of opioid selection and dosing in managing labor analgesia, effectiveness of different regional anesthetic techniques, non-pharmacologic management, and psycho-social support for these patients."	( Opioid Use Disorder in Pregnant Patients. Nathan, N, 2022)	0.72
" The standard-of-care treatment is daily maintenance dosing of sublingual buprenorphine (BUP-SL) or oral methadone (MET)."	( Experience and response to a randomised controlled trial of extended-release injectable buprenorphine versus sublingual tablet buprenorphine and oral liquid methadone for opioid use disorder: protocol for a mixed-methods evaluation. Cowden, F; Day, E; Gilvarry, E; Johnstone, S; Kelleher, M; Lowry, N; Marsden, J; Mitcheson, L; Murray, R, 2022)	1.13
" Compared to other opioids, methadone has a longer duration of action, rapid onset, extended dosing intervals, high oral bioavailability, low cost, lack of active metabolites, and action on multiple receptors."	( What we know and what we don't know about the perioperative use of methadone in children and adolescents. Boisvert-Plante, V; Einhorn, LM; Ingelmo, P; Poulin-Harnois, C, 2023)	1.44
"2%) of methadone patients indicated that some form of multi-day take home dosing was offered at their clinic, and 45."	( Nothing really changed: Arizona patient experience of methadone and buprenorphine access during COVID. Andres, HJ; Arredondo, C; Bentele, KG; Brady, BR; Coles, H; Downer, M; Garcia, RC; Garnett, I; Granillo, B; Lutz, R; Mahoney, A; Meyerson, BE; Russell, DM; Samorano, S, 2022)	1.42
"0 % did so while also on a dosage of either buprenorphine or methadone, with 28."	( Understanding motivations and use typologies of gabapentin with opioid agonist medications. Buttram, ME; Ellis, MS; Qureshi, R, 2023)	1.15
"This study aimed to evaluate the effectiveness of flexible take-home dosing of buprenorphine/naloxone (BUP/NX) and methadone standard model of care in reducing depressive symptoms in people with prescription-type opioid use disorder (POUD)."	( Effects of Buprenorphine/Naloxone and Methadone on Depressive Symptoms in People with Prescription Opioid Use Disorder: A Pragmatic Randomised Controlled Trial. Bastien, G; Brissette, S; Hassan, AN; Jutras-Aswad, D; Le Foll, B; Ledjiar, O; Lim, R; Marsan, S; McAnulty, C; Socias, ME; Talbot, A, 2023)	1.39
"gov identifier: NCT03033732), a pragmatic randomised controlled trial comparing flexible take-home dosing of BUP/NX and methadone standard model of care for reducing opioid use in people with POUD."	( Effects of Buprenorphine/Naloxone and Methadone on Depressive Symptoms in People with Prescription Opioid Use Disorder: A Pragmatic Randomised Controlled Trial. Bastien, G; Brissette, S; Hassan, AN; Jutras-Aswad, D; Le Foll, B; Ledjiar, O; Lim, R; Marsan, S; McAnulty, C; Socias, ME; Talbot, A, 2023)	1.39
" Future studies should evaluate the optimal methadone dosing and overlap time to prevent opioid IWS."	( Characterization of early versus late opioid iatrogenic withdrawal syndrome in critically ill children transitioning from fentanyl -infusions to methadone. Gupta, N; Hintze, TD; Johnson, PN; Lim, SY; Miller, JL; Neely, SB, )	0.59
" The restrictions on methadone availability including take-home dosing were loosened during the COVID-19 pandemic although there have been concerns about the high street value of diverted methadone."	( Examination of methadone involved overdoses during the COVID-19 pandemic. Kaufman, DE; Kennalley, AL; McCall, KL; Piper, BJ, 2023)	1.58
" Many settings across North America relaxed restrictions for take-home dosing during the COVID-19 pandemic and have reported consistent or improved patient outcomes."	( Incremental expenditures attributable to daily dispensation and witnessed ingestion for opioid agonist treatment in British Columbia: 2014-20. Dale, L; Guerra-Alejos, BC; Kurz, M; Min, JE; Nosyk, B; Piske, M, 2023)	0.91
"The introduction of depot buprenorphine for the treatment of opioid dependence allows for reduced dosing frequency compared with conventional treatments, such as oral methadone and sublingual buprenorphine-naloxone."	( Exploring patient experience and satisfaction with depot buprenorphine formulations: A mixed-methods study. Allen, E; Altobelli, G; Holmwood, C; Johnson, J; Samadian, S, 2023)	1.11
" There were mixed experiences with the ability for depot buprenorphine to 'hold' participants throughout the dosing interval."	( Exploring patient experience and satisfaction with depot buprenorphine formulations: A mixed-methods study. Allen, E; Altobelli, G; Holmwood, C; Johnson, J; Samadian, S, 2023)	0.91
" The potential for disconnection from services and mixed experiences of efficacy throughout the dosing period may negatively influence patient experience."	( Exploring patient experience and satisfaction with depot buprenorphine formulations: A mixed-methods study. Allen, E; Altobelli, G; Holmwood, C; Johnson, J; Samadian, S, 2023)	0.91
"Policymakers should consider patients' perspectives to foster a more patient-centered approach to methadone dosing that is safe, flexible, and accommodating to a diverse array of patients' needs."	( Patient experiences of COVID-19-induced changes to methadone treatment in a large community-based opioid treatment program in Baltimore. Abidogun, TM; Belcher, AM; Cole, TO; Greenblatt, AD; Kleinman, M; Magidson, JF; Massey, E; Seitz-Brown, CJ, 2023)	1.38
" The community-driven research (CDR) online survey collected information on how patient take-home methadone dosing and in-person drug testing, counseling, and clinic visit frequency changed prior to COVID-19 (before March 2020) to during COVID-19 (June and July 2020)."	( Patient experiences of methadone treatment changes during the first wave of COVID-19: a national community-driven survey. Brothers, S; Coulter, A; Palayew, A; Simon, C; Strichartz, K; Vincent, L; Voyles, N, 2023)	1.44
" In this exploratory analysis, we examined the effect of recent cannabis use on opioid use, craving, and withdrawal symptoms, in individuals participating in a trial comparing flexible buprenorphine/naloxone (BUP/NX) take-home dosing model to witnessed ingestion of methadone."	( Differential effect of cannabis use on opioid agonist treatment outcomes: Exploratory analyses from the OPTIMA study. Bakouni, H; Bastien, G; Brissette, S; Elkrief, L; Hébert, FO; Jutras-Aswad, D; Le Foll, B; Ledjiar, O; Lim, R; Marsan, S; McAnulty, C; Socias, ME, 2023)	1.09
" Using an attentional bias (AB) task with both pain and opioid cues, we evaluated a cognitive bias modification (CBM) task administered during regularly scheduled medications for OUD (mOUD) dosing visits."	( Integrating cognitive bias modification for pain and opioid cues into medication for opioid use disorder clinical care: Feasibility, acceptability, and preliminary results. Heapy, AA; MacLean, RR; Meyerovich, J; Sofuoglu, M; Szollosy, SK; Waters, AJ; Wolkowicz, N, 2023)	0.91
"Methadone treatment is the most effective evidence-based treatment for opioid use disorder (OUD), but challenges related to dosing and premature treatment dropout argue for adjunct interventions to improve outcomes."	( Effectiveness of Conditioned Open-label Placebo With Methadone in Treatment of Opioid Use Disorder: A Randomized Clinical Trial. Belcher, AM; Billing, AS; Cole, TO; Colloca, L; Epstein, DH; Greenblatt, AD; Hoag, SW; Kaptchuk, TJ; Magder, L; Massey, E; Rotrosen, J; Wagner, M; Weintraub, E; Wickwire, EM; Wish, ED; Wooten, W, 2023)	2.6
"The methadone dosage varied from 5 to 20 mg."	( Retrospective Study of the Safety and Efficacy of Intraoperative Methadone for Pain Management in Patients Undergoing Elective Intracranial Surgery. Graf, J; Pillai, P; Propp, D; Sran, JK; Vacaru, A; Vandse, R, 2023)	1.71
"We identified three themes related to patients' internal relationships to methadone: patients (1) viewed methadone as a bridge to opioid-free recovery, (2) believed that long-term methadone damages the body, and (3) felt that methadone increases craving for cocaine; and three themes related to their external relationships with opioid treatment programs and society at large: patients (4) viewed daily dosing as burdensome, (5) feared methadone inaccessibility could trigger relapse, and (6) experienced stigma from friends, family, and peers."	( Transitioning off methadone: A qualitative study exploring why patients discontinue methadone treatment for opioid use disorder. Chander, G; Pytell, JD; Stoller, KB; Thakrar, AP; Walters, V; Weiss, RD, 2023)	1.47
" Primary outcomes were retention in treatment at 1, 3, 6, 12, and 24 months, treatment adherence (measured through doses taken as prescribed, dosing visits attended, and biological measures), or extra-medical opioid use (measured by urinalysis and self-report)."	( Buprenorphine versus methadone for the treatment of opioid dependence: a systematic review and meta-analysis of randomised and observational studies. Clark, B; Degenhardt, L; Farrell, M; Hickman, M; Kimber, J; Larance, B; Leppan, O; Macpherson, G; Martino-Burke, D; Nielsen, S; Zahra, E, 2023)	1.23
" An internal database of patient demographics and dosing events was collected during the normal treatment process."	( Comparison of Regular Versus After Hours Admissions to a 24-hour Opioid Treatment Program. Sherrick, RC, )	0.13
" However, up-to-half of participants reported uncertainty regarding the appropriate dosage of MOUD and its impact on the fetus and/or neonate."	( Attitudes Toward Medication for Opioid Use Disorder Among Pregnant and Postpartum Women and People Seeking Treatment. Banks, DE; Cavazos-Rehg, P; Fentem, A; Filiatreau, L; Li, X; Paschke, M; Woolfolk, C, )	0.13
" We describe a patient with opioid use disorder who presented to the emergency department in precipitated withdrawal who completed a same-day methadone induction with next-day dosing at an opioid treatment program as part of an emergency department methadone protocol."	( Methadone Induction for a Patient With Precipitated Withdrawal in the Emergency Department: A Case Report. Church, B; Clark, R; Friedmann, P; Mohn, W; Potee, R; Soares, WE, )	1.78
"Regulatory changes made during the COVID-19 public health emergency (PHE) that relaxed criteria for take-home dosing (THD) of methadone offer an opportunity to improve quality of care with a lifesaving treatment."	( Clinics Optimizing MEthadone Take-homes for opioid use disorder (COMET): Protocol for a stepped-wedge randomized trial to facilitate clinic level changes. Bao, Y; Choi, S; Cleland, CM; D'Aunno, T; Hong, S; Knopf, E; Neighbors, CJ; O'Grady, MA; Ramsey, KS, 2023)	1.44
" However, a growing body of evidence and clinical experience shows that some patients may benefit from twice-daily ("split") dosing to produce more stable symptoms and minimize side effects, independent of serum peak-to-trough levels."	( Individualizing methadone treatment with split dosing: An underutilized tool. Braun, HM; Potee, RA, 2023)	1.26
", i) the analgesic agent is identical to the OAT medication, and ii) the opioid agent is dosed above 1/6th morphine equivalent dose of the OAT medication."	( Rescue Analgesia for Opioid-Dependent Individuals on Opioid Agonist Treatment during Hospitalization: Adherence to Guideline Treatment. Arnet, I; Dürsteler, KM; Grossmann, F; Hersberger, KE; Jaiteh, C, 2023)	0.91
" This strategy facilitates dosing of LAB before hospital discharge when risk of opioid relapse and overdose are significant."	( Inpatient Low-dose Transitions From Full Agonist Opioids Including Methadone Onto Long-acting Depot Buprenorphine: Case Series From a Multicenter Clinical Trial. Brady, KT; Frank, CA; Levin, FR; Litwin, AH; Nunes, EV; Nunez, J; Roth, P; Schade, M; Seval, N; Springer, SA; Strong, M, )	0.37
" This involved longer take-home intervals for methadone and buprenorphine doses as well as a reduction in supervised dosing and drug screening."	( Flexible delivery of opioid agonist treatment during COVID-19 in Norway: qualitative and quantitative findings from an online survey of provider experiences. Bech, AB; Clausen, T; McDonald, R, 2023)	1.17
" In individual cases, patients' substance use was identified as key factor necessitating a reintroduction of supervised dosing and drug screening."	( Flexible delivery of opioid agonist treatment during COVID-19 in Norway: qualitative and quantitative findings from an online survey of provider experiences. Bech, AB; Clausen, T; McDonald, R, 2023)	0.91
" Hospitalization offers a monitored setting for methadone initiation, however dosing practices and safety are not well described."	( Rapid Methadone Induction in a General Hospital Setting: A Retrospective, Observational Analysis. Adams, ZM; Casey, S; Gale, E; Lambert, E; Omede, FO; Regan, S; Wakeman, SE, 2023)	1.65
" Patients preferred dosing at the van over the clinic because they were able to "get in and out" faster."	( "Get in and get out, get on with life": Patient and provider perspectives on methadone van implementation for opioid use disorder treatment. Castellanos, S; Joshi, N; Knight, KR; Lambdin, BH; Shapiro, B; Steiger, S; Suen, LW, 2023)	1.14
"A cross-sectional, descriptive study was conducted using the daily methadone dosing records from shelters in Tshwane between March 2020 and September 2020."	( Methadone use for acute opioid withdrawal in Tshwane shelters during the COVID-19 lockdown. Bhoora, U; Janse van Rensburg, M; Siemens, JA, 2023)	2.59
"This study demonstrates variability in methadone dosing regimens among shelter residents."	( Methadone use for acute opioid withdrawal in Tshwane shelters during the COVID-19 lockdown. Bhoora, U; Janse van Rensburg, M; Siemens, JA, 2023)	2.62