tramadol profile

Tramadol: A narcotic analgesic proposed for severe pain. It may be habituating. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

tramadol : A racemate consisting of equal amounts of (R,R)- and (S,S)-tramadol. A centrally acting synthetic opioid analgesic, used (as the hydrochloride salt) to treat moderately severe pain. The (R,R)-enantiomer exhibits ten-fold higher analgesic potency than the (S,S)-enantiomer. Originally developed by Gruenenthal GmbH and launched in 1977, it was subsequently isolated from the root bark of the South African tree Nauclea latifolia. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

(R,R)-tramadol : A 2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol in which both stereocentres have R-configuration; the (R,R)-enantiomer of the racemic opioid analgesic tramadol, it exhibits ten-fold higher analgesic potency than the (S,S)-enantiomer. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

ID Source	ID
PubMed CID	33741
CHEMBL ID	1066
CHEBI ID	75725
CHEBI ID	9648
SCHEMBL ID	7464
MeSH ID	M0021764

Synonym
BIDD:GT0075
rel-tramadol
chebi:75725 ,
CHEMBL1066
AB00640024-11
(1r,2r)-2-[(dimethylamino)methyl]-1-[3-(methyloxy)phenyl]cyclohexanol
tradolan
tiparol
einecs 248-319-6
cg-315e
tramadolum [inn-latin]
cyclohexanol, 2-((dimethylamino)-1-(3-methoxyphenyl)-, cis-(+-)-
tramadol [inn:ban]
cyclohexanol, 2-((dimethylamino)methyl)-1-(3-methoxyphenyl)-, cis-(+-)-
ralivia er
ralivia flashtab
cyclohexanol, 2-((dimethylamino)methyl)-1-(m-methoxyphenyl)-
tramadol
C07153
27203-92-5
DB00193
NCGC00159343-02
smr000436547
(1r,2r)-2-dimethylaminomethyl-1-(3-methoxy-phenyl)-cyclohexanol
MLS000333190
hsdb 7047
zytram
HMS2090D10
e265
D08623
tramadol (inn)
amanda (tn)
AKOS005066335
bdbm50176259
(1r,2r)-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol
123154-38-1
(+)-tramadol
unii-0ng5ttm63p
cyclohexanol-2-((dimethylamino)methyl)-1-(3-methoxyphenyl)-, trans-(+-)-
e 382
(+)-trans-2-(dimethylaminomethyl)-1-(m-methoxyphenyl)cyclohexanol
(+)-(r,r)-trans-
cyclohexanol, 2-(dimethylaminomethyl)-1-(m-methoxyphenyl)-, (+)-(e)-
0ng5ttm63p ,
tramadol, (+)-
(+)-trans-tramadol free base
e-265
u-26255a
amanda
ets6103
ets-6103
(r,r)-tramadol
trapidol
39j1lgj30j ,
tramadis
tramadon
u 26255a
tradonal odis
ryzolt
tramadolum
e 265
tramadol contramid
cg 315e
contramid
biomadol
unii-39j1lgj30j
labesfal
racemic tramadol
cis-tramadol
tramaliv
(+-)-tramadol
FT-0675346
HMS2803D04
FT-0604438
tramadol [who-dd]
tramadol [vandf]
tramadol [inn]
tramadol [jan]
(+/-)-cis-2-((dimethylamino)methyl)-1-(m-methoxyphenyl)cyclohexanol
(+/-)-tramadol
tramadol [mi]
(1r,2r)-2-(dimethylaminomethyl)-1-(3-methoxyphenyl)-cyclohexanol
cis tramadol
TVYLLZQTGLZFBW-ZBFHGGJFSA-N
SCHEMBL7464
tilodol
maxitram
181289-58-7
(1r,2r)-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexan-1-ol
DTXSID90858931 ,
cyclohexanol, 2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)-, (1r,2r)-rel-
sustained-release tramadol
(1r,2r)-2-((dimethylamino)methyl)-1-(3-methoxyphenyl)cyclohexanol
(+)-(r,r)-tramadol
(r,r) tramadol
Q407592
(1r,2r)-2-((dimethylamino)methyl)-1-(3-methoxyphenyl)cyclohexan-1-ol
n02ax02
(1rs,2rs)-2-((dimethylamino)methyl)-1-(3-methoxyphenyl)-cyclo-hexanol
tramadolum (inn-latin)
(+-)-2-((dimethylamino)methyl)-1-(3-methoxyphenyl)cyclohexanol
chebi:9648
tramadolo
dtxcid20809618
tramadolum (latin)
DTXSID401167150

Excerpt	Reference	Relevance
"Tramadol is a synthetic opioid and poisoning is increasing around the world day by day. "	( Effects of naloxone and diazepam on blood glucose levels in tramadol overdose using generalized estimating equation (GEE) model; (an experimental study). Amirabadizadeh, A; Askari, M; Farrokhfall, K; Foadoddini, M; Mehrpour, O; Miri-Moghaddam, E; Nakhaee, S, 2021)	2.31
"Tramadol is an opioid extensively used to treat moderate to severe pain; however, prolonged therapy is associated with several tissues damage. "	( Chronic exposure to tramadol induces cardiac inflammation and endothelial dysfunction in mice. Abd-Elhamid, TH; Ali, M; Bakr, MH; Farrag, AA; Mahmoud, AR; Radwan, E; Shaltout, AS, 2021)	2.39
"Tramadol is a widely used synthetic opioid for moderate to severe pain. "	( The effects of quercetin on seizure, inflammation parameters and oxidative stress in acute on chronic tramadol intoxication. Askari, M; Farrokhfall, K; Foadoddini, M; Mehrpour, O; Miri-Moghaddam, E; Nakhaee, S, 2021)	2.28
"Tramadol is a weak opioid that produces analgesic effect via both the μ-opioid receptor (MOR) and non-opioid targets. "	( Involvement of the Peripheral μ-Opioid Receptor in Tramadol-Induced Constipation in Rodents. Chiba, H; Fujita, M; Hasegawa, M; Kitaura, M; Kobayashi, M; Koike, K; Mishima, H; Morioka, Y; Suzuki, T; Takenouchi, S; Yasufuku, K, 2021)	2.32
"Tramadol is a synthetic analogue of codeine and stimulates neurodegeneration in several parts of the brain that leads to various behavioral impairments. "	( Combined molecular, structural and memory data unravel the destructive effect of tramadol on hippocampus. Abdollahifar, MA; Aghajanpour, F; Aliaghaei, A; Eskandarian Boroujeni, M; Ezi, S; Hassani Moghaddam, M; Khatmi, A; Khodagholi, F; Meftahi, GH; Mirbehbahani, SH; Soltani, R; Toreyhi, H, 2022)	2.39
"Tramadol is a bitter atypical opioid analgesic drug and is prescribed to treat postoperative pain in children. "	( A randomised controlled trial of a novel tramadol chewable tablet: pharmacokinetics and tolerability in children. Khan, N; Lim, LY; Nguyen, MN; Salman, S; Sommerfield, A; Sommerfield, D; Tang, EKY; von Ungern Sternberg, BS; Yoo, O, 2022)	2.43
"Tramadol is a centrally acting synthetic analgesic with a multimode of action used to help treat moderate to severe pain. "	( Tramadol Use in Perioperative Care and Current Controversies. Esfandiary, L; Henson, C; Ogbemudia, B; Przkora, R; Qu, G; Victor, S, 2022)	3.61
"Tramadol is a widely used weak opioid; however, the evidence for its safety profile in respiratory system needs additional information. "	( Association between tramadol use and risk of pneumonia in the middle-aged and elderly populations: a propensity-score matched cohort study. Ding, X; Li, X; Lu, N; Wang, Y; Wu, Z, 2022)	2.49
"Tramadol is a commonly used opioid with a potential of addiction and abuse. "	( Short-term mortality following tramadol poisonings in Denmark. Andersen, JT; Christensen, MB; Jimenez Solem, E; Petersen, J; Petersen, TS; Schelde, AB; Sørensen, AMS, 2022)	2.45
"Tramadol is an opioid pain medication used to treat moderate to severe pain. "	( Comparison of urine trace element levels in tramadol addiction alone and its co-abuse with cigarette and opium in Western Iran. Ahmadi-Jouybari, T; Azadi, N; Farnia, V; Khanegi, M; Mansouri, B; Nakhaee, S, 2022)	2.43
"Tramadol (TM) is a centrally long-acting analgesic class of opioids extensively being used among the population."	( Protective and restorative potency of diosmin natural flavonoid compound against tramadol-induced testicular damage and infertility in male rats. Anwar, MM; Laila, IMI, 2023)	1.86
"Tramadol is a synthetic opioid with centrally acting analgesic activity that alleviates moderate to severe pain and treats withdrawal symptoms of the other opioids. "	( Effect of tramadol on apoptosis and synaptogenesis in hippocampal neurons: The possible role of µ-opioid receptor. Akbarabadi, A; Hadjighassem, M; Hosseindoost, S; Khalifeh, S; Mokri, A; Mousavi, SM; Sadat-Shirazi, MS; Zarrindast, MR, 2022)	2.57
"Tramadol is an analgesic mainly used in humans; it is also commonly used in dogs, despite some controversy over its clinical efficacy."	( Ex-vivo study of the percutaneous absorption of a tramadol formulation through feline inner pinna skin. Beuve, MS; Espana, B; Pin, D; Prouillac, C, 2022)	1.7
"Tramadol is an analgesic drug that is mainly excreted in the urine. "	( Synthesis and comparison of three photocatalysts for degrading tramadol as an analgesic and widely used drug in water samples. Abedi, MR; Ebrahimi, M; Kazemi, F; Zamani, HA, 2023)	2.59
"Tramadol is a common anesthetic used to treat cancer pain, including endometrial cancer, but its function in endometrial cancer remains unclear. "	( Mitochondrial Dysfunction Involved in the Cytotoxicity of Tramadol in Human Endometrial Carcinoma Cells. Chen, JL; Huang, YH; Lai, HC; Liu, LC; Wu, ZF; Wu, ZS, 2022)	2.41
"Tramadol is a useful analgesic which acts as a serotonin and noradrenaline reuptake inhibitor in addition to μ-opioid receptor agonist. "	( Tramadol regulates the activation of human platelets via Rac but not Rho/Rho-kinase. Doi, T; Enomoto, Y; Hioki, T; Hori, T; Iida, H; Iwama, T; Kim, W; Kozawa, O; Matsushima-Nishiwaki, R; Mizutani, D; Nakashima, D; Ogura, S; Onuma, T; Tachi, J; Tanabe, K; Tokuda, H; Ueda, K; Yamaguchi, S, 2023)	3.8
"Tramadol is a centrally acting analgesic."	( High-dose tramadol conversion to buprenorphine-naloxone. Boyd, CT; Cassidy-Vu, L; Fagan, EB; Kirk, JK; McRae, LP; Strickland, HE, )	1.26
"Tramadol is a potent narcotic analgesic reportedly used in multiple sports to reduce exertional pain and confer a performance advantage. "	( Tramadol is a performance-enhancing drug in highly trained cyclists: a randomized controlled trial. Fennell, CRJ; Mauger, AR; Smith, SA; Thomas, T, 2023)	3.8
"Tramadol (TRA) is an analgesic prescribed for treating mild to moderate pains, the abuse of which has increased in recent years. "	( Role of apoptosis and autophagy in mediating tramadol-induced neurodegeneration in the rat hippocampus. Gholami, M; Hayes, AW; Jamaati, H; Motaghinejad, M; Sureda, A, 2023)	2.61
"Tramadol abuse is a common problem in the Middle East in conjunction with smoking. "	( Neurological Effects of Combining Low Toxic Dose of Tramadol and Nicotine: An Animal Model Evidence of Endoplasmic Reticulum Stress. Abu-El-Rub, EM; Gharaibeh, MH; Ghorab, D; Helaly, AM; Khasawneh, RR; Matalqah, LM; Yehya, A, 2023)	2.6
"Tramadol is a commonly utilized analgesic in the United States. "	( Atypical Withdrawal Symptoms after Abrupt Tramadol Discontinuation: A Case Report. Cheng, S; Sams, C, 2023)	2.62
"Tramadol is a synthetic analog of codeine, mainly prescribed to alleviate mild to moderate pains."	( Tramadol induces apoptosis, inflammation, and oxidative stress in rat choroid plexus. Abdollahifar, MA; Aliaghaei, A; Mehranpour, M; Moghaddam, MH; Salehi, M, 2023)	3.07
"Tramadol is a centrally acting analgesic with a lower risk of addiction compared to opioids. "	( Clinical and Laboratory Factors Related to Seizure and Serotonin Toxicity in Tramadol Intoxication: An Egyptian Study. Abdelkawy, K; Abdeshafy, MM; Ali, AA; Elbarbry, F; Elsabaa, RM, 2023)	2.58
"Tramadol is a weak opioid that is commonly used for chronic low back pain (LBP). "	( Duplicated tramadol use in chronic low back pain: A nationwide cross-sectional study. Jeong, KH; Jung, SY; Koo, H; Lee, MT; Lee, S; Seon, JY; You, SH, 2020)	2.39
"Tramadol is a dual-mechanism (opiate and monoamine reuptake inhibition) analgesic. "	( Comparing the Pharmacokinetics of 2 Novel Intravenous Tramadol Dosing Regimens to Oral Tramadol: A Randomized 3-Arm Crossover Study. Atiee, GJ; Harnett, M; Lu, L; Reines, SA; Ryan, M, 2020)	2.25
"Tramadol is an effective oral and intravenous analgesia with recent evidence supporting the use of IP tramadol (IPT)."	( Intraperitoneal Tramadol in Abdominal Surgery: A Systematic Review. Autagavaia, V; Barazanchi, AWH; Hill, AG; MacFater, WS; Otutaha, B; Xia, W, 2020)	1.63
"Tramadol is a synthetic analog of codeine used to treat pain of moderate to severe intensity and is reported to have neurotoxic potential. "	( Neurobehavioral Consequences Associated with Long Term Tramadol Utilization and Pathological Mechanisms. Chawla, P; Raj, K; Singh, S, 2019)	2.2
"Tramadol (TRA) is a widely used human pharmaceutical and a well-established emerging pollutant and its potential genotoxic and cytotoxic effects on humans as well as its fate in aqueous systems demand full investigation. "	( Assessing the human risk and the environmental fate of pharmaceutical Tramadol. Hela, D; Konstantinou, F; Thoma, A; Vlastos, D; Αntonopoulou, Μ, 2020)	2.23
"Tramadol is a common analgesic, frequently used for relieving moderate or severe pain and widely used to delay ejaculation. "	( Tramadol administration induced hippocampal cells apoptosis, astrogliosis, and microgliosis in juvenile and adult male mice, histological and immunohistochemical study. Abdel Mola, AF; Hussein, OA; Rateb, A, 2020)	3.44
"Tramadol is a low-level opioid increasingly recommended to treat moderate-to-severe acute and chronic pain. "	( Safety Events Associated with Tramadol Use Among Older Adults with Osteoarthritis. Kraemer, S; Musich, S; Schaeffer, JA; Slindee, L; Wang, SS; Yeh, CS, 2021)	2.35
"Tramadol abuse is an increasingly alarming phenomenon among Egyptian Community especially among workers and drivers. "	( Tramadol abuse among workers in an industrial city in mid-Nile Delta region, Egypt. Abd-Elkader, MR; El-Sallamy, RM; El-Sawy, H; Gad, EA; Kabbash, IA, 2020)	3.44
"Tramadol is a centrally acting opioid analgesic that is extensively used. "	( Pomegranate Seeds Extract Possesses a Protective Effect against Tramadol-Induced Testicular Toxicity in Experimental Rats. Badawy, MA; El Omri, A; Hassan, NA; Hassan, NS; Massoud, AA; Metwally, FG; Minisy, FM; Oishi, H; Omara, EA; Shawki, HH, 2020)	2.24
"Tramadol is a centrally acting analgesic drug, used for the management of moderate to severe pain in a variety of diseases. "	( Tramadol Promotes Oxidative Stress, Fibrosis, Apoptosis, Ultrastructural and Biochemical alterations in the Adrenal Cortex of Adult Male Rat with Possible Reversibility after Withdrawal. Aboregela, AM; Alabiad, MA; El Shaer, DF; Shalaby, AM, 2020)	3.44
"Tramadol is a synthetic analogue of codeine that is often prescribed for the treatment of mild to moderate pains. "	( Tramadol: a Potential Neurotoxic Agent Affecting Prefrontal Cortices in Adult Male Rats and PC-12 Cell Line. Abdollahifar, MA; Aghajanpour, F; Aliaghaei, A; Amini, A; Boroujeni, ME; Ezi, S; Jahanian, A; Khatmi, A; Mirbehbahani, SH; Soltani, R; Toreyhi, H, 2020)	3.44
"Tramadol is a synthetic analogue of codeine, mostly prescribed for the alleviation of mild to moderate pains. "	( Tramadol exposure upregulated apoptosis, inflammation and autophagy in PC12 cells and rat's striatum: An in vitro- in vivo approach. Abdollahifar, MA; Aghajanpour, F; Akhlaghpasand, M; Aliaghaei, A; Boroujeni, ME; Ezi, S; Heidari, MH; Khatmi, A; Mirbehbahani, SH; Soltani, R, 2020)	3.44
"Tramadol is an opioid used as an analgesic for treating moderate or severe pain. "	( Toxicology of tramadol following chronic exposure based on metabolomics of the cerebrum in mice. Gao, L; Liu, G; Liu, J; Shao, Z; Xia, W; Xu, E; Yuan, H, 2020)	2.36
"Tramadol is a synthetic opioid drug used in the treatment of chronic and acute pain. "	( Is pain temporary and glory forever? Detection of tramadol using dried blood spot in cycling competitions. Bigard, X; Daali, Y; Déglon, J; Faiss, R; Garcia, A; González-Ruiz, V; Rossi, F; Rudaz, S; Salamin, O; Saugy, M, 2020)	2.25
"Tramadol is a centrally acting dual-mechanism (opioid and monoamine reuptake inhibition) analgesic that has been noted to have a lower risk of abuse compared to conventional opioids such as morphine. "	( IV tramadol: A novel option for US patients with acute pain-A review of its pharmacokinetics, abuse potential and clinical safety record. Harnett, M; Lu, L; Reines, SA, )	2.2
"Tramadol is a synthetic opioid with analgesic activity of its own as well as being metabolically activated by CYP2D to O-desmethyltramadol (ODMST) an opioid receptor agonist."	( Centrally administered CYP2D inhibitors increase oral tramadol analgesia in rats. El-Sherbeni, AA; McMillan, DM; Richards, J; Tyndale, RF, 2020)	1.53
"Tramadol is a schedule IV, monoaminergic and μ-opioid-receptor analgesic with unique pharmacology properties. "	( Clinical Tolerability and Safety of Tramadol in Hospitalized Patients. Ajayi, TA; Atayee, RS; Edmonds, KP; Mohan, N, 2020)	2.28
"Tramadol is an atypical opioid with a dual mechanism, and has low drug liking compared to conventional opioids."	( Tramadol non-medical use in Four European countries: A comparative analysis. Black, JC; Dart, RC; Iwanicki, JL; May, KP; Schwarz, J, 2020)	2.72
"Tramadol (TRA) is a weak opioid analgesic, prescribed to relieve mild to moderately severe pain. "	( Tramadol sensing in non-invasive biological fluids using a voltammetric electronic tongue and an electrochemical sensor based on biomimetic recognition. Aghoutane, Y; Bouchikhi, B; Burhan, H; Diouf, A; El Bari, N; Sen, F, 2021)	3.51
"Tramadol is a commonly prescribed analgesic drug for treatment of moderate to severe pain with less potential for dependence and respiratory depression."	( The plausible mechanisms of tramadol for treatment of COVID-19. Abo Kamer, AM; Abo-Saif, MA; El-Aasr, M; El-Ashmawy, NE; Goda, AE; Haggag, YA; Lashin, AA; Mostafa, TM; Okasha, KM; Tawfik, HO, 2021)	1.64
"Tramadol is an opioid used as an analgesic for treating moderate or severe pain. "	( Changes on proteomic and metabolomic profile in serum of mice induced by chronic exposure to tramadol. Gao, L; Jiang, S; Liu, G; Liu, J; Xia, W; Xu, E; Yuan, H; Zhang, X, 2021)	2.28
"Tramadol is a widely used analgesic with additional antidepressant and anxiolytic effects. "	( Traces of tramadol in water impact behaviour in a native European fish. Douda, K; Grabic, R; Grabicová, K; Horký, P; Hubená, P; Randák, T; Santos, MES; Slavík, O, 2021)	2.47
"Tramadol appears to be an effective drug for the management of PE with a low propensity for serious adverse events. "	( Safety and efficacy of "on-demand" tramadol in patients with premature ejaculation: an updated meta-analysis. Bora, GS; Devana, SK; Mavuduru, RS; Sharma, AP; Sharma, G; Singh, SK; Tyagi, S, )	1.85
"Tramadol is an opioid analgesic that binds to mu-opioid receptors and inhibits the uptake of norepinephrine and serotonin. "	( A Case Report of Hypoglycemia Following a Tramadol Overdose in a Non-Diabetic Patient. Bush, JS; Clendening, AM; Weant, KA, 2022)	2.43
"Tramadol is a weak opioid mu agonist."	( Tiletamine/zolazepam and dexmedetomidine with tramadol provide effective general anesthesia in rats. Durongphongtorn, S; Jampachaisri, K; Limprasutr, V; Pacharinsak, C; Sharp, P, 2021)	1.6
"Tramadol is a centrally acting synthetic opioid analgesic and SNRI (serotonin/norepinephrine reuptake-inhibitor) that structurally resembles codeine and morphine. "	( Chronic Exposure to Tramadol Induces Neurodegeneration in the Cerebellum of Adult Male Rats. Abdollahifar, MA; Aghajanpour, F; Aliaghaei, A; Boroujeni, ME; Ezi, S; Farahani, RM; Fathi, M; Khatmi, A; Khodagholi, F; Mirbehbahani, SH; Soltani, R; Vakili, K, 2021)	2.39
"Tramadol is an opioid used in the treatment of moderate to moderately severe pain. "	( Neonatal Exposure to Tramadol through Mother's Breast Milk. Gesseck, AM; Hendricks-Muñoz, KD; Nanco, CR; Peace, MR; Poklis, JL; Wolf, CE; Xu, J, 2021)	2.38
"Tramadol is a widely used synthetic opioid. "	( The effects of naloxone, diazepam, and quercetin on seizure and sedation in acute on chronic tramadol administration: an experimental study. Amirabadizadeh, A; Askari, M; Brent, J; Farrokhfall, K; Foadoddini, M; Megarbane, B; Mehrpour, O; Miri-Moghaddam, E; Nakhaee, S, 2021)	2.28
"Tramadol is an effective pain medication prodrug with a complex mechanism of action that requires extensive metabolism."	( Acute Pain Crisis Caused by Tramadol Remdesivir Drug-Drug Interaction. Feely, M; Ho, I; Miller, G; Teoli, D; Thompson, V; Vlaminck, B; Wright, J, 2021)	1.64
"Tramadol is an opioid medication used to treat moderately severe pain. "	( Physiologically Based Pharmacokinetic Modeling to Assess the Impact of CYP2D6-Mediated Drug-Drug Interactions on Tramadol and O-Desmethyltramadol Exposures via Allosteric and Competitive Inhibition. Cicali, B; Cristofoletti, R; Dow, P; Long, T; Michaud, V; Schmidt, S; Turgeon, J, 2022)	2.37
"Tramadol is a centrally acting analgesic drug able to prevent nociceptor sensitization when administered into the temporomandibular joint (TMJ) of rats. "	( The anti-inflammatory effect of tramadol in the temporomandibular joint of rats. Clemente-Napimoga, JT; de Araujo, DR; Fogaça, CL; Freitas, FF; Lamana, SMS; Macedo, CG; Napimoga, MH; Nascimento, APC; Quinteiro, MS, 2017)	2.18
"Tramadol hydrochloride is a centrally acting synthetic opioid analgesic drug and is used to treat chronic pain. "	( A disposition kinetic study of Tramadol in bile duct ligated rats in perfused rat liver model. Ardakani, YH; Esmaeili, Z; Ghazi-Khansari, M; Lavasani, H; Mohammadi, S; Nezami, A; Rouini, MR, 2017)	2.18
"Tramadol is an opioid analgesic licensed for use in moderate to severe pain. "	( Tramadol with or without paracetamol (acetaminophen) for cancer pain. Derry, S; Moore, RA; Wiffen, PJ, 2017)	3.34
"Tramadol is an opioid analgesic also used for veterinary treatments."	( A physiologically based model for tramadol pharmacokinetics in horses. Abbiati, RA; Cagnardi, P; Manca, D; Ravasio, G; Villa, R, 2017)	1.46
"Tramadol is an analgesic agent that is mainly used to treat moderate to severe pain. "	( Involvement of NMDA receptors in the antidepressant-like effect of tramadol in the mouse forced swimming test. Akbarian, R; Chamanara, M; Dehpour, AR; Ghasemi, M; Imran-Khan, M; Norouzi-Javidan, A; Ostadhadi, S, 2017)	2.13
"Tramadol is an opioid and a serotonin reuptake inhibitor drug. "	( [Serious adverse drug reactions with tramadol reported to the French pharmacovigilance database between 2011 and 2015]. Abadie, D; Dautriche, A; Masmoudi, K; Micallef, J; Montastruc, F; Montastruc, JL; Moulis, F; Pierre, S; Rousseau, V; Vigier, C, 2017)	2.17
"Tramadol is an opioid drug that, unlike classic opioids, also modulates the monoaminergic system by inhibiting noradrenergic and serotoninergic reuptake. "	( Discovery and development of tramadol for the treatment of pain. Berrocoso, E; Bravo, L; Mico, JA, 2017)	2.19
"Tramadol is an opioid agonist which can be potentially used for maintenance treatment of patients with opioid use disorders. "	( Tramadol for maintenance in opioid dependence: A retrospective chart review. Balhara, YPS; Lal, R; Sarkar, S; Varshney, M, )	3.02
"Tramadol use is an overwhelming problem in Egypt with tremendous medical and social consequences especially among youth. "	( Opioid Use Disorders Attributed to Tramadol Among Egyptian University Students. Abdelghani, M; Bassiony, MM; El-Gohari, H; Hassan, MS; Salah El-Deen, GM; Youssef, UM, )	1.85
"Tramadol is a prodrug that acts through noradrenaline and serotonin reuptake inhibition, with a weak opioid component added by its metabolite O-desmethyltramadol."	( Comparative pharmacology and toxicology of tramadol and tapentadol. Barbosa, J; Carvalho, F; Dinis-Oliveira, RJ; Faria, J; Moreira, R; Queirós, O, 2018)	1.46
"Tramadol is an effective opioid analgesic but is associated with risks such as drug dependence and unexpected toxicity arising from genetic differences in metabolism."	( Development of a column-switching LC-MS/MS method of tramadol and its metabolites in hair and application to a pharmacogenetic study. Bae, JW; Choi, M; Jang, JH; Jeong, CH; Lee, S; Park, B; Seo, YH; Yu, H, 2018)	1.45
"Tramadol is a commonly prescribed analgesia with a few adverse effects."	( Hyponatraemia Associated with Tramadol Use: A Case Report. Khow, KSF; Yong, TY, 2018)	1.49
"Tramadol is an analgesic with monoamine reuptake inhibition and μ-opioid receptor activation. "	( Acute tramadol enhances brain activity associated with reward anticipation in the nucleus accumbens. Asari, Y; Iijima, T; Ikeda, Y; Okubo, Y; Suzuki, H; Tateno, A, 2018)	2.4
"Tramadol is a synthetic semi-opioid analgesic, interacting with serotonergic, adrenergic and opioid receptors to reduce the pain but its short half-life in vivo may reduce patient compliance in case of chronic pains."	( Controlled-release in-situ gel forming formulation of tramadol containing chitosan-based pro-nanogels. Ashrafi, H; Azadi, A; Barati, M; Mohammadi Samani, S; Pourtalebi Jahromi, L, 2018)	1.45
"Tramadol is a synthetic analogue of codeine and a weak opioid receptor (μ) agonist that can cause seizures even in commonly used doses."	( Demographic Characteristics and Functional Performance of the Kidneys and Hearts of Patients with Acute Tramadol Toxicity. Ashkezari, MD; Farahmand, B; Mohammadpour, A; Shokrzadeh, M, 2019)	1.45
"Tramadol is an analgesic used to treat moderate to severe pain caused by cancer, osteoarthritis, and other musculoskeletal diseases. "	( Tramadol-induced hepato- and nephrotoxicity in rats: Role of Curcumin and Gallic acid as antioxidants. Almasmari, AA; El-Banna, SG; Sheweita, SA, 2018)	3.37
"Tramadol is an opioid agonist with activation monoaminergic properties. "	( Pharmacokinetic changes of tramadol in rats with hepatotoxicity induced by ethanol and acetaminophen in perfused rat liver model. Ardakani, YH; Esmaeili, Z; Ghazi-Khansari, M; Hassanzadeh, G; Lavasani, H; Mohammadi, S; Nezami, A; Rouini, MR, 2019)	2.25
"Tramadol is an opioid used as analgesic for treating moderate or sever pain. "	( Chronic exposure to the opioid tramadol induces oxidative damage, inflammation and apoptosis, and alters cerebral monoamine neurotransmitters in rats. Mahmoud, AM; Mohamed, HM, 2019)	2.24
"Tramadol is an atypical prescription-only (but unscheduled under Canada's narcotics law) opioid analgesic and not subject to controls for other (eg, strong) opioids."	( Tramadol dispensing patterns and trends in Canada, 2007-2016. Fischer, B; Jones, W; Kurdyak, P, 2019)	2.68
"Tramadol is a centrally acting weak μ-opioid receptor analgesic and is a racemic mixture of (+)-tramadol and (-)-tramadol enantiomers."	( An overview of tramadol and its usage in pain management and future perspective. Bajaj, S; Kumar, MS; Subedi, M; Yc, M, 2019)	1.59
"Tramadol also acts as an opioid receptor agonist and an NMDA receptor antagonist, but few studies have evaluated the effects of tramadol on EA."	( Effects of tramadol on emergence agitation after general anesthesia for nasal surgery: A retrospective cohort study. Choi, SJ; In, CB; Lee, SJ; Sung, TY, 2019)	1.63
"Tramadol is a widely prescribed analgesic that influences both opioid and monoamine neurotransmission. "	( Tramadol and the risk of seizure: nested case-control study of US patients with employer-sponsored health benefits. Dormuth, CR; Gomes, T; Juurlink, DN; Mamdani, MM; Morrow, RL; Paterson, M, 2019)	3.4
"Tramadol is an analgesic usually prescribed for the management of pain, with a certain risk of addiction in chronic patients. "	( The role of emulsion parameters in tramadol sustained-release from electrospun mats. Abraham, GA; Giannetti, R; Rivero, G, 2019)	2.23
"Desmetramadol is an investigational analgesic consisting of (+) and (-) enantiomers of the tramadol metabolite O-desmethyltramadol (M1). "	( Desmetramadol Has the Safety and Analgesic Profile of Tramadol Without Its Metabolic Liabilities: Consecutive Randomized, Double-Blind, Placebo- and Active Comparator-Controlled Trials. Johnson, MS; Kahn, SJ; Maeda, DY; Schuler, AD; Searle, SL; Webster, LR; Zebala, JA, 2019)	1.54
"Tramadol is a synthetic opioid analgesic used to treat chronic and acute pain."	( Behaviour and cardiac response to stress in signal crayfish exposed to environmental concentrations of tramadol. Buřič, M; Císař, P; Grabic, R; Grabicová, K; Kozák, P; Kubec, J; Kuklina, I; Ložek, F; Randák, T, 2019)	1.45
"Tramadol (TR) is an analgesic drug used to treat moderate-to-severe pain but it induces seizure even at therapeutic doses. "	( Caffeine attenuates seizure and brain mitochondrial disruption induced by Tramadol: the role of adenosinergic pathway. Ahangar, N; Bameri, B; Fallah, M; Mohammadi, H; Samadi, M; Shaki, F, 2021)	2.29
"Tramadol is an opioid with lipophilic characteristics that freely crosses the placenta. "	( [Neonatal abstinence syndrome after maternal use of tramadol]. de Wit, D; Koomen-Botman, I, 2013)	2.08
"Tramadol is a synthetic opiate and a centrally acting weak m-opioid receptor agonist. "	( Comparison of efficacy between buprenorphine and tramadol in the detoxification of opioid (heroin)-dependent subjects. Balhara, YP; Chawla, JM; Jain, R; Lal, R; Pal, H; Schooler, N, )	1.83
"Tramadol is an option in the case patients will not respond satisfactorily to NSAIDs."	( Pharmacologic treatment of hand-, knee- and hip-osteoarthritis. Bobacz, K, 2013)	1.11
"Tramadol is an atypical analgesic with monoamine and modest mu opioid agonist activity. "	( Efficacy of extended-release tramadol for treatment of prescription opioid withdrawal: a two-phase randomized controlled trial. Babalonis, S; Campbell, C; Lofwall, MR; Nuzzo, PA; Siegel, A; Walsh, SL, 2013)	2.12
"Tramadol is a synthetic opioid, widely used for post-surgical and chronic pain. "	( A suicidal poisoning due to tramadol. A metabolic approach to death investigation. Barbera, N; Bosco, A; Fisichella, M; Indorato, F; Romano, G; Spadaro, G, 2013)	2.13
"Tramadol is a weak opioid used as a step 2 analgesic, approved in France for moderate to severe pain. "	( ["Serious" adverse drug reactions with tramadol: a 2010-2011 pharmacovigilance survey in France]. Abadie, D; Durrieu, G; Montastruc, JL; Roussin, A, )	1.84
"Tramadol is an opioid analgesic that, in combination with acetaminophen, has been approved since 2011 for the treatment of non-cancer pain in Japan."	( [Efficacy of tramadol/acetaminophen medication for central post-stroke pain]. Hirano, M; Kajita, Y; Nakahara, N; Noda, H; Takebayashi, S; Tanei, T; Wakabayashi, T, 2013)	1.48
"Tramadol is a central analgesic with a unique pharmacological profile in that it is an opioid agonist and an inhibitor of serotonin and norepinephrine reuptake. "	( Tramadol abuse in a binge pattern in a young depressed woman. Ferrari, A; Licata, M; Palazzoli, F; Tiraferri, I, 2014)	3.29
"Tramadol is a widely used analgesic opioid for moderate-to-severe pain due to its efficacy and safety. "	( Postmortem redistribution of tramadol and O-desmethyltramadol. Carvalho, F; Costa, I; Dinis-Oliveira, RJ; Guedes de Pinho, P; Moreira, R; Oliveira, A; Teixeira, HM, )	1.87
"Tramadol hydrochloride is a common prescription pain reliever that is structurally similar to morphine and codeine with its analgesic effects identified as a mu-receptor agonist. "	( The association between tramadol hydrochloride misuse and other substances use in an adolescent population: Phase I of a prospective survey. Bidel, Z; Carson, KV; Nazarzadeh, M, 2014)	2.15
"Tramadol is a drug that is widely prescribed because of its low abuse potential, but physicians need to be aware of its significant potential to cause SS because it inhibits serotonin reuptake."	( Serotonin syndrome after the use of tramadol and ziprasidone in a patient with a deep brain stimulator for Parkinson disease. Assaly, R; El-Okdi, NS; Ghose, A; Karanovic, D; Lumbrezer, D, )	1.13
"Tramadol is a centrally acting analgesic that is often used in conjunction with nonsteroidal anti-inflammatory drugs (NSAIDs). "	( The effect of tramadol and indomethacin coadministration on gastric barrier function in dogs. Blikslager, AT; Hill, TL; Lascelles, BD; Law, JM, )	1.93
"Tramadol (T) is a centrally acting atypical opioid used for treatment of dogs. "	( Pharmacokinetics of tramadol and its major metabolite after intramuscular administration in piglets. Giorgi, M; Kim, TW; Marini, C; Meligrana, M; Vullo, C, 2014)	2.17
"Tramadol is a common analgesic, widely prescribed because of its efficiency and safety. "	( Cardiogenic shock due to acute tramadol intoxication. Iriart, X; Jalal, Z; Mouton, JB; Perdreau, E; Thambo, JB, 2015)	2.15
"Tramadol is a potent analgesic drug which interacts with mu-opioid and has low effect on other opioid receptors. "	( Inhibition and structural changes of liver alkaline phosphatase by tramadol. Azizi, L; Eslami, M; Hosseini, AS; Katebian, E; Khazaei, N; Minai-Tehrani, D; Taheri, M; Yazdi, F, 2014)	2.08
"Tramadol/paracetamol is a fixed-dose combination prescribed for the relief of moderate to severe pain. "	( The pharmacokinetics of the effervescent vs. conventional tramadol/paracetamol fixed-dose combination tablet in patients after total gastric resection. Burchardt, P; Cieśla, S; Grabowski, T; Grześkowiak, E; Karbownik, A; Kokot, ZJ; Murawa, D; Murawa, P; Połom, K; Szałek, E; Urbaniak, B; Więckiewicz, A; Wolc, A, 2014)	2.09
"Tramadol is an atypical centrally acting analgesic agent available as both oral and parenteral preparations. "	( Pharmacokinetics of tramadol after subcutaneous administration in a critically ill population and in a healthy cohort. Chapman, MJ; Dooney, NM; Ludbrook, GL; O'Connor, SN; Ong, J; Ramkumar, T; Somogyi, AA; Sundararajan, K; Upton, RN, 2014)	2.17
"Tramadol is a commonly used opioid analgesic in dogs, particularly in dogs with a compromised immune system. "	( Effects of tramadol and o-desmethyltramadol on canine innate immune system function. Amorim, J; Axiak-Bechtel, SM; DeClue, A; Dodam, J; Donaldson, R; Honaker, A; Lino, G; Monibi, F; Tsuruta, K, 2015)	2.25
"Tramadol is a synthetic non-opiate analgesic drug and effective for many kinds of chronic and acute pain. "	( Bioavailability of tramadol hydrochloride after administration via different routes in rats. Wang, X; Zhang, H; Zhang, Q; Zhao, Y, 2014)	2.17
"Tramadol is a centrally acting analgesic whose action is mediated by both agonistic activity at opioid receptors and inhibitory activity on neuronal reuptake of monoamines. "	( Transport characteristics of tramadol in the blood-brain barrier. Deguchi, Y; Higuchi, K; Kitamura, A; Okura, T, 2014)	2.14
"Tramadol is a synthetic codeine analogue used as an analgesic in human and veterinary medicine. "	( Clinical pharmacokinetics of tramadol and main metabolites in horses undergoing orchiectomy. Cagnardi, P; Ferraresi, C; Pecile, A; Ravasio, G; Villa, R; Zani, DD; Zonca, A, 2014)	2.14
"Tramadol is a weak opioid analgesic whose use has increased rapidly, and it has been associated with adverse events of hypoglycemia."	( Tramadol use and the risk of hospitalization for hypoglycemia in patients with noncancer pain. Azoulay, L; Fournier, JP; Montastruc, JL; Suissa, S; Yin, H, 2015)	3.3
"Tramadol is a centrally acting analgesic prescribed off-label for the treatment of premature ejaculation (PE). "	( Tramadol for premature ejaculation: a systematic review and meta-analysis. Cantrell, A; Cooper, K; Dickinson, K; Frodsham, L; Hood, C; Kaltenthaler, E; Martyn-St James, M; Wylie, K, 2015)	3.3
"Tramadol is an effective analgesic that is widely used in clinical practice."	( Tramadol and its metabolite m1 selectively suppress transient receptor potential ankyrin 1 activity, but not transient receptor potential vanilloid 1 activity. Matoba, M; Minami, K; Miyano, K; Murakami, S; Ohbuchi, K; Shiraishi, S; Uezono, Y; Yamaguchi, T; Yamamoto, M; Yokoyama, T, 2015)	2.58
"Tramadol is a weak mu-opioid agonist and inhibits reuptake of noradrenaline and serotonin (5HT)."	( Tramadol for postoperative pain treatment in children. Meyer-Frießem, C; Pogatzki-Zahn, E; Reichl, SU; Schnabel, A; Zahn, PK, 2015)	2.58
"Tramadol is a novel, synthetic opioid receptor agonist with serotonin-norepinephrine reuptake inhibitor properties that is often prescribed acutely for painful conditions. "	( Tramadol for the treatment of fibromyalgia. MacLean, AJ; Schwartz, TL, 2015)	3.3
"Tramadol is a commonly used centrally acting analgesic associated with seizures and suspected to cause serotonin toxicity in overdose."	( Tramadol overdose causes seizures and respiratory depression but serotonin toxicity appears unlikely. Isbister, GK; Ryan, NM, 2015)	3.3
"Tramadol is a synthetic opioid which has analgesic efficacy in the postoperative pain. "	( Effect of the CYP2D6 gene polymorphism on postoperative analgesia of tramadol in Han nationality nephrectomy patients. Dong, H; Liu, DD; Lu, SJ; Song, CY; Zhang, R; Zhang, YZ, 2015)	2.09
"Tramadol is an atypical opioid analgesic with low potential for tolerance and addiction. "	( Design, synthesis and biological evaluation of N-phenylalkyl-substituted tramadol derivatives as novel μ opioid receptor ligands. Fu, W; Li, W; Liu, JG; Qian, YY; Shen, Q; Xu, XJ, 2015)	2.09
"Tramadol is a centrally acting weak μ opioid agonist that has few of the adverse side effects common to other opioids. "	( Efficacy of Tramadol as a Sole Analgesic for Postoperative Pain in Male and Female Mice. Kennedy, LH; Na, JJ; Nemzek-Hamlin, JA; Wolfe, AM, 2015)	2.24
"Tramadol is an analgesic that is used worldwide for pain, but its mechanisms of action have not been fully elucidated. "	( What is the main mechanism of tramadol? Minami, K; Ogata, J; Uezono, Y, 2015)	2.15
"Tramadol is a synthetic, centrally acting, opiate-like analgesic that is structurally related to codeine and morphine. "	( PHARMACOKINETICS OF TRAMADOL HYDROCHLORIDE AND ITS METABOLITE O-DESMETHYLTRAMADOL FOLLOWING A SINGLE, ORALLY ADMINISTERED DOSE IN CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS). Barbosa, L; Boonstra, JL; Cox, SK; Gulland, FM; Johnson, SP; Martin-Jimenez, T; Van Bonn, WG, 2015)	2.18
"Tramadol is a centrally acting opioid analgesic that is prone to polymorphic metabolism via cytochrome P450 (CYP) 2D6. "	( Differential Consequences of Tramadol in Overdosing: Dilemma of a Polymorphic Cytochrome P450 2D6-Mediated Substrate. Srinivas, NR, 2015)	2.15
"Tramadol is a centrally acting analgesic and requires frequent dosing. "	( In vitro and preclinical assessment of factorial design based nanoethosomes transgel formulation of an opioid analgesic. Ahmed, S; Ali, A; Aqil, M; Gull, A; Sarim Imam, S; Zafar, A, 2016)	1.88
"Tramadol is a synthetic and centrally active analgesic. "	( Hypo and hyperglycemia among tramadol overdose patients in Loghman Hakim Hospital, Tehran, Iran. Aghabiklooei, A; Aghapour, S; Khorasani, AG; Mahdavinejad, A; Mashayekhian, M; Nasouhi, S; Pajoumand, A; Rahimi, M; Razi, P; Talaie, H, 2015)	2.15
"Tramadol is an analgesic agent used in man and a number of veterinary species. "	( Effects of age on the pharmacokinetics of tramadol and its active metabolite, O-desmethyltramadol following intravenous administration to foals. Knych, HK; McKemie, DS; Steffey, EP; White, AM, 2016)	2.14
"Tramadol is a weak opioid analgesic indicated for the treatment of moderate to severe pain. "	( Refractory Cardiogenic Shock During Tramadol Poisoning: A Case Report. Belin, N; Capellier, G; Chocron, S; Clairet, AL; Piton, G, 2017)	2.17
"Tramadol is a centrally acting synthetic analgesic. "	( The effects of tramadol on hepatic ischemia/reperfusion injury in rats. El-Fayoumi, HM; Gamal, S; Mahmoud, MF; Shaheen, MA, )	1.93
"Tramadol hydrochloride is a centrally acting analgesic used for the treatment of moderate-to-severe pain. "	( Evaluation of the route dependency of the pharmacokinetics and neuro-pharmacokinetics of tramadol and its main metabolites in rats. Gholami, M; Lavasani, H; Rouini, M; Sheikholeslami, B, 2016)	2.1
"Tramadol is a unique analgesic medication, available in variety of formulations, with both monoaminergic reuptake inhibitory and opioid receptor agonist activity increasingly prescribed worldwide as an alternative for high-affinity opioid medication in the treatment of acute and chronic pain. "	( Trends in Tramadol: Pharmacology, Metabolism, and Misuse. Blanco, K; Cho, AK; Khalil, MA; Miotto, K; Rawson, R; Sasaki, JD, 2017)	2.3
"Tramadol is a well-known and effective analgesic. "	( Tramadol: Effects on sexual behavior in male rats are mainly caused by its 5-HT reuptake blocking effects. Esquivel Franco, DC; Olivier, B; Olivier, JD; Oosting, R; Sarnyai, Z; Waldinger, M, 2017)	3.34
"Tramadol hydrochloride is a centrally-acting synthetic opioid analgesic binding to specific opioid receptors. "	( [Mucoadhesive buccal films of tramadol for effective pain management]. Fan, CR; Li, C; Li, XQ; Pan, AW; Wang, JB; Ye, ZM; Zhang, RB, )	1.86
"Tramadol abuse is a public health problem in Egypt."	( Cognitive Impairment and Tramadol Dependence. Abdalla, A; Abdelghani, M; Bassiony, MM; El-Gohari, H; Hassan, MS; Ibrahim, DH; Salah El-Deen, GM; Youssef, UM, 2017)	1.48
"Tramadol is a synthetic, centrally acting low-affinity agonist of μ-opioid receptors in humans. "	( Tramadol, an Opioid Receptor Agonist: An Inhibitor of Growth, Morphogenesis, and Biofilm Formation in the Human Pathogen, Candida albicans. Karuppayil, SM; Kathwate, GH, 2016)	3.32
"Tramadol is a widely used opioid analgesic. "	( Assessment of abuse liability of Tramadol among experienced drug users: Double-blind crossover randomized controlled trial. Das, M; Dhawan, A; Jain, R; Kaur, A, )	1.86
"Tramadol is a centrally acting clinically effective analgesic, with a weak opioid receptor affinity. "	( Effects of 5,7-dihydroxytryptamine lesion of the dorsal raphe nucleus on the antidepressant-like action of tramadol in the unpredictable chronic mild stress in mice. Belzung, C; Bodard, S; Chalon, S; Coubard, S; Yalcin, I, 2008)	2
"Tramadol 100 mg is a beneficial additive to lignocaine for IVRA since it shortened the onset of sensory block, enhanced the tourniquet tolerance and improved the perioperative analgesia."	( Tramadol as an adjuvant to intravenous regional anesthesia with lignocaine. AbuZeid, HA; Al-Ghamdi, A; Ismail, SA; Mowafi, HA; Siddiqui, AK, 2008)	3.23
"Tramadol is a centrally acting analgesic which is used mainly for the treatment of moderate or severe pain. "	( Involvement of L-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effect of tramadol in the rat forced swimming test. Bortolatto, CF; Jesse, CR; Nogueira, CW; Rocha, JB; Savegnago, L, 2008)	2
"Tramadol is a particularly promising candidate."	( Experimental studies of potential analgesics for the treatment of chemotherapy-evoked painful peripheral neuropathies. Bennett, GJ; Naso, L; Xiao, W, )	0.85
"Tramadol is a centrally acting analgesic with a dual mode of action. "	( [Tramadol intoxication and its toxicological effect]. Guan, DW; Wang, HX; Wang, L; Wang, MB, 2008)	2.7
"Tramadol is a centrally acting analgesic drug that has been used clinically for the last two decades to treat pain in humans. "	( Evaluation of tramadol and its main metabolites in horse plasma by high-performance liquid chromatography/fluorescence and liquid chromatography/electrospray ionization tandem mass spectrometry techniques. Braca, A; De Leo, M; Giorgi, M; Manera, C; Saccomanni, G, 2009)	2.16
"Tramadol is a centrally acting analgesic with half-life of approximately 6 h; therefore, it requires frequent dosing."	( Polymeric matrix system for prolonged delivery of tramadol hydrochloride, part I: physicochemical evaluation. Ammar, HO; El-Nahhas, SA; Ghorab, M; Kamel, R, 2009)	1.33
"Tramadol is a synthetic opioid agonist used extensively in human and, to a lesser extent, veterinary medicine throughout the world. "	( Pharmacokinetics and efficacy of intravenous and extradural tramadol in dogs. Beccaglia, M; Cagnardi, P; Gallo, M; Isola, M; Montesissa, C; Ravasio, G; Vettorato, E; Villa, R; Zonca, A, 2010)	2.05
"Tramadol hydrochloride is a widely prescribed, centrally acting analgesic marketed in over 90 countries. "	( Tramadol: basic pharmacology and emerging concepts. Burke, RS; Reeves, RR, 2008)	3.23
"Tramadol seems to be a potential useful analgesic for term neonates and infants, but has limited indications in (extreme) preterm neonates."	( Neonatal clinical pharmacology: recent observations of relevance for anaesthesiologists. Allegaert, K; de Hoon, J; Naulaers, G; Van De Velde, M, 2008)	1.07
"Tramadol is an opioid analgesic used for the treatment of moderate to severe pain."	( Formulation design and optimization of novel taste masked mouth-dissolving tablets of tramadol having adequate mechanical strength. Bhalekar, MR; Madgulkar, AR; Padalkar, RR, 2009)	1.3
"Tramadol is a synthetic, centrally acting analgesic for the treatment of moderate to severe pain. "	( Multiply organ dysfunction syndrome due to tramadol intoxication alone. Li, CS; Song, YG; Wang, SQ, 2009)	2.06
"Tramadol hydrochloride is a centrally acting analgesic agent with two distinct mechanisms of action, a weak opioid agonist and an inhibitor of monoamine neurotransmitter reuptake, which produces significant analgesic effect synergistically. "	( [Effectiveness of oral tramadol hydrochloride for chronic non-malignant pain]. Hanada, M; Kitahara, M; Kojima, K; Kuriyama, Y; Ohmura, A, 2009)	2.11
"Tramadol is a useful option to treat non-malignant chronic pain, especially considering its very low abuse potential and a more acceptable side effect profile compared to non-steroidal anti-inflammatory drugs and opioids."	( [Effectiveness of oral tramadol hydrochloride for chronic non-malignant pain]. Hanada, M; Kitahara, M; Kojima, K; Kuriyama, Y; Ohmura, A, 2009)	2.11
"Tramadol is a weak opioid analgesic, which is generally considered to be safe. "	( Tramadol dependence: a survey of spontaneously reported cases in Sweden. Ahlner, J; Hägg, S; Jönsson, AK; Tjäderborn, M, 2009)	3.24
"Tramadol is a centrally acting analgesic used in the treatment of moderate to severe acute or chronic pain."	( Multidrug poisoning involving nicotine and tramadol. Buschmann, CT; Riesselmann, B; Solarino, B; Tsokos, M, 2010)	1.34
"Tramadol is an analgesic drug, and its mechanism of action is believed to be mediated by the mu-opioid receptor. "	( Spinal 5-HT7 receptors play an important role in the antinociceptive and antihyperalgesic effects of tramadol and its metabolite, O-Desmethyltramadol, via activation of descending serotonergic pathways. Akgül, O; Aypar, U; Dogrul, A; Kozak, O; Kurt, E; Sahin, A; Seyrek, M; Sizlan, A; Yanarates, O; Yildirim, V, 2010)	2.02
"Tramadol is a relatively new drug that provides analgesia by opioid (mu), serotonin, and norepinephrine pathways, with minimal adverse effects."	( Pharmacokinetics of intravenous and oral tramadol in the bald eagle (Haliaeetus leucocephalus). Cox, SK; Jones, MP; Martin-Jimenez, T; Souza, MJ, 2009)	1.34
"Tramadol is a centrally acting analgesic drug used in veterinary and human clinical practice. "	( Determination of tramadol and metabolites by HPLC-FL and HPLC-MS/MS in urine of dogs. Del Carlo, S; Giorgi, M; Macchia, M; Manera, C; Saba, A; Saccomanni, G, 2010)	2.14
"Tramadol is a widely prescribed drug. "	( Current trends in tramadol-related fatalities, Tehran, Iran 2005-2008. Akhgari, M; Bahmanabadi, L; Iravani, FS; Jokar, F, 2010)	2.14
"Tramadol is a well tolerated and effective analgesic used to treat moderate to severe pain. "	( Bioequivalence evaluation of single doses of two tramadol formulations: a randomized, open-label, two-period crossover study in healthy Brazilian volunteers. dos Reis Serra, CH; Kano, EK; Mori Koono, EE; Porta, V; Schramm, SG; Silva, Mde F, 2010)	2.06
"Tramadol is an atypical, mixed mechanism analgesic used to treat moderate to severe pain. "	( Effects of repeated tramadol and morphine administration on psychomotor and cognitive performance in opioid-dependent volunteers. Bigelow, GE; Lanier, RK; Lofwall, MR; Mintzer, MZ; Strain, EC, 2010)	2.13
"Tramadol is an atypical, mixed-mechanism analgesic involving both opioid and catecholamine processes that appears to have low abuse potential and may be useful as a treatment for opioid dependence."	( Physical dependence potential of daily tramadol dosing in humans. Bigelow, GE; Lanier, RK; Lofwall, MR; Mintzer, MZ; Strain, EC, 2010)	2.07
"Tramadol is a synthetic codeine analogue used as an analgesic in human and veterinary medicine, but not approved for use in cats. "	( Pharmacokinetics, intraoperative effect and postoperative analgesia of tramadol in cats. Beccaglia, M; Cagnardi, P; Carli, S; Fonda, D; Gallo, M; Luvoni, GC; Ravasio, G; Vettorato, E; Villa, R; Zonca, A, 2011)	2.05
"Tramadol is an analgesic drug that can be used in postoperative analgesia, but it has important side effects, such as nausea and vomiting whose incidence can range from 0% to 50%."	( Intravenous and subcutaneous tramadol for inguinal herniorrhaphy: comparative study. de Azevedo, VL; de Oliveira, OE; dos Santos, TO; Estrela, TG; Figueiredo, Gda S; Oliveira, G, )	1.14
"Tramadol is an opioid-like analgesic with relatively mild side effects. "	( Evaluation of dosages and routes of administration of tramadol analgesia in rats using hot-plate and tail-flick tests. Blankenship-Paris, T; Cannon, CZ; Hoenerhoff, MJ; King-Herbert, AP; Kissling, GE, 2010)	2.05
"Tramadol is a commonly prescribed synthetic opioid analgesic. "	( Isolated tramadol overdose associated with Brugada ECG pattern. Asinger, RW; Bertog, SC; Bilden, EF; Cole, JB; Sattiraju, S, 2012)	2.24
"Tramadol is an opioid analgesic considered to induce fewer side effects than other compounds of this class. "	( Quantification in postmortem blood and identification in urine of tramadol and its two main metabolites in two cases of lethal tramadol intoxication. Charlier, C; De Backer, B; Denooz, R; Renardy, F, 2010)	2.04
"Tramadol is a relatively new analgesic that is available in an inexpensive, oral form, and is not controlled."	( Tramadol use in zoologic medicine. Cox, SK; Souza, MJ, 2011)	2.53
"Tramadol is an atypical opioid with monoamine re-uptake inhibition properties. "	( Tramadol increases extracellular levels of serotonin and noradrenaline as measured by in vivo microdialysis in the ventral hippocampus of freely-moving rats. Bloms-Funke, P; Cremers, TI; Dremencov, E; Tzschentke, TM, 2011)	3.25
"Tramadol is a centrally acting analgesic used in the prevention and treatment of moderate to severe pain. "	( Use of two sulfonthalein dyes in the extraction-free spectrophotometric assay of tramadol in dosage forms and in spiked human urine based on ion-pair reaction. Basavaiah, K; Rajendraprasad, N; Ramesh, PJ; Revannasiddappa, HD; Vinay, KB; Xavier, CM, 2012)	2.05
"Tramadol is a centrally acting opiate analgesic that has not been well studied in avian species. "	( Pharmacokinetics of tramadol hydrochloride and its metabolite O-desmethyltramadol in peafowl (Pavo cristatus). Black, PA; Cox, SK; Junge, RE; Macek, M; Tieber, A, 2010)	2.13
"Tramadol is an analgesic with a dual mechanism of action and has several side effects, one of which is epileptic seizure."	( Epileptic seizure following IV tramadol in a patient with mental retardation and cerebellar ataxia. Bilimgut, B; Dikmen, B; Eruyar, S; Inan, N; Ulger, G; Yarkan Uysal, H, 2011)	2.1
"Tramadol is an unscheduled atypical analgesic that acts as an agonist at μ-opioid receptors and inhibits monoamine reuptake. "	( Discriminative stimulus effects of tramadol in humans. Bigelow, GE; Duke, AN; Lanier, RK; Strain, EC, 2011)	2.09
"Tramadol is a centrally acting analgesic available throughout the world. "	( Extended-release formulations of tramadol in the treatment of chronic pain. Pergolizzi, JV; Raffa, RB; Taylor, R, 2011)	2.09
"Tramadol is a synthetic, centrally acting analgesic for the treatment of moderate to severe pain. "	( Near-fatal tramadol cardiotoxicity in a CYP2D6 ultrarapid metabolizer. Allorge, D; Broly, F; Elkalioubie, A; Fourrier, F; Garat, A; Robriquet, L; Wiart, JF, 2011)	2.2
"Tramadol is a weak opioid analgesic used as a step two analgesic, approved in France for the treatment of moderate to severe pain in adult patients. "	( [Severe hypoglycemia induced by tramadol: two new cases of an unlisted side effect]. Bornet, C; Boyer, M; Castellan, D; Chiche, L; Default, A; Durand, JM; Harlé, JR; Jean, R; Jean-Pastor, MJ; Lanfranchi, MA; Rouby, F; Taugourdeau, S, 2011)	2.1
"Tramadol is an atypical central analgesic with a mixed mechanism of action offering many advantages over conventional opioids."	( Double-phase hydrogel for buccal delivery of tramadol. El-Feky, G; Kamel, R; Mahmoud, A, 2012)	1.36
"Tramadol is a centrally acting analgesic, whose mechanism of action involves opioid-receptor activation. "	( Inhibition of L-type calcium current by tramadol and enantiomers in cardiac myocytes from rats. Medei, E; Nascimento, JH; Raimundo, JM; Sudo, RT; Trachez, MM; Zapata-Sudo, G, 2011)	2.08
"Tramadol is a widely used analgesic that stimulates the μ opioid receptor and inhibits serotonin and noradrenalin reuptake. "	( Effect of tramadol on pain-related behaviors and bladder overactivity in rodent cystitis models. Homan, T; Kyotani, J; Oka, M; Oyama, T, 2012)	2.22
"Tramadol is an atypical opioid analgesic used in the treatment of mild to moderate pain. "	( Recurrent seizures in tramadol intoxication: implications for therapy based on 100 patients. Brent, J; Hafezi, P; Mousavi-Fatemi, K; Shadnia, S; Soltaninejad, K, 2012)	2.14
"Tramadol is a centrally acting analgesic that acts via μ-opioid agonism and by blocking the neuronal uptake of norepinephrine and serotonin. "	( Tramadol antinociception is potentiated by clonidine through α₂-adrenergic and I₂-imidazoline but not by endothelin ET(A) receptors in mice. Andurkar, SV; Gendler, L; Gulati, A, 2012)	3.26
"Tramadol is a prescription analgesic that activates mu opioid and monoamine receptor systems. "	( Pharmacodynamic profile of tramadol in humans: influence of naltrexone pretreatment. Craig, LB; Lofwall, MR; Nuzzo, PA; Siegel, AJ; Stoops, WW; Walsh, SL, 2012)	2.12
"Tramadol is a weak opioid according to the World Health Organization pain ladder step II. "	( High use of tramadol in Germany: an analysis of statutory health insurance data. Hoffmann, F; Tholen, K, 2012)	2.2
"Tramadol is a potent analgesic. "	( Estimation of the minimum effective dose of tramadol for postoperative analgesia in infants using the continual reassessment method. Allen Finley, G; Dai, Y; Huang, Z; Lei, D; Yin, Y; Zuo, Y, 2012)	2.08
"Tramadol is a synthetic, centrally acting analgesic indicated for moderate to severe pain."	( Comparison of oral midazolam with oral tramadol, triclofos and zolpidem in the sedation of pediatric dental patients: an in vivo study. Bhatnagar, G; Bhatnagar, S; Das, UM, )	1.12
"Tramadol is an additive recently found at high concentration levels in street heroin seizures in Egypt."	( Development and validation of a new GC-MS method for the detection of tramadol, O-desmethyltramadol, 6-acetylmorphine and morphine in blood, brain, liver and kidney of Wistar rats treated with the combination of heroin and tramadol. Chericoni, S; El-Shihi, TH; Emara, MM; Giorgi, M; Giusiani, M; Mahdy, T, 2012)	1.33
"Tramadol is a synthetic centrally-acting opioid analgesic. "	( An open label trial of the effects and safety profile of extended-release tramadol in the management of chronic pain. Hsieh, YJ; Hsu, SK; Lin, CJ; Yeh, CC, 2012)	2.05
"Tramadol is a synthetic opioid that has scarcely been researched in cats, although its clinical use appears beneficial."	( Case studies of compounded Tramadol use in cats. Boggess, D; Clark, J; Fackler, B; Jordan, D; Pinelli, C; Ray, J, )	1.15
"Tramadol is a synthetic opioid used in human medicine, and to a lesser extent in veterinary medicine, for the treatment of both acute and chronic pain. "	( Pharmacokinetics and pharmacodynamics of tramadol in horses following oral administration. Corado, CR; Knych, HK; McKemie, DS; Sams, R; Scholtz, E, 2013)	2.1
"Tramadol is an effective treatment for patients with PE and represents a promising alternative to the currently used oral pharmacologic agents. "	( The use of tramadol "on-demand" for premature ejaculation: a systematic review. Malde, S; Wong, BL, 2013)	2.22
"Tramadol is an atypical opioid analgesic widely used in small animal practice. "	( Effects of a single bolus intravenous dose of tramadol on minimum alveolar concentration (MAC) of sevoflurane in dogs. Inoue, H; Ishizuka, T; Itami, T; Kawase, K; Miyoshi, K; Tamaru, N; Tamura, J; Umar, MA; Yamashita, K, 2013)	2.09
"Tramadol Hydrochloride is a widely-used centrally acting analgesic drug, which has some features of being a P-gp substrate. "	( Lack of evidence for involvement of P-glycoprotein in brain uptake of the centrally acting analgesic, tramadol in the rat. Hamidi, M; Lavasani, H; Rouini, MR; Sharifzadeh, M; Sheikholeslami, B, 2012)	2.04
"Tramadol is a central-acting analgesic associated with nausea and vomiting. "	( Dexamethasone effect on postoperative pain and tramadol requirement after thyroidectomy. Assunção, J; Barros, A; Fontes Ribeiro, CA; Oliveira, FC; Pereira, FC; Vale, CP; Ventura, C, 2013)	2.09
"Tramadol is a widely used analgesic, but its mechanism of action is not completely understood. "	( The inhibitory effects of tramadol on muscarinic receptor-induced responses in Xenopus oocytes expressing cloned M(3) receptors. Kaibara, M; Minami, K; Murasaki, O; Shiga, Y; Shigematsu, A; Shiraishi, M; Uezono, Y, 2002)	2.06
"Tramadol is reported to be an effective analgesic and to have a side-effect profile similar to morphine, but is currently not licensed for paediatric use in the UK."	( Tramadol for pain relief in children undergoing tonsillectomy: a comparison with morphine. Engelhardt, T; Johnston, G; Steel, E; Veitch, DY, 2003)	2.48
"Tramadol is a safe and efficient analgesic molecule in children."	( [Comparative study of two Tramadol prescription protocols for postoperative analgesia in children]. Ben Ghachem, M; el Jaouani, H; Jelel, C; Kaabachi, O; Safi, H, 2002)	1.34
"Tramadol is a centrally acting opioid analgesic which is increasingly used in Sweden. "	( [Treatment with tramadol can give rise to dependence and abuse]. Dahlqvist, R; Näslund, S, 2003)	2.11
"Tramadol hydrochloride is an analgesic with mu receptor activity suitable for administration to children as oral drops. "	( Pharmacokinetics of oral tramadol drops for postoperative pain relief in children aged 4 to 7 years--a pilot study. Payne, KA; Roelofse, JA; Shipton, EA, 2002)	2.06
"Tramadol is an analgesic drug that stimulates opioid receptors and inhibits reuptake of serotonin and noradrenaline."	( Tramadol inhibits rat detrusor overactivity caused by dopamine receptor stimulation. Andersson, KE; Pehrson, R, 2003)	2.48
"Tramadol is a centrally acting analgesic agent used in the treatment of mild to moderate pain. "	( Fatal overdoses of tramadol: is benzodiazepine a risk factor of lethality? Clarot, F; Goullé, JP; Proust, B; Vaz, E, 2003)	2.09
"Tramadol is an opioid drug metabolised in phase I by cytochrome P450 (CYP) enzymes, of which CYP2D6 is mainly responsible for the O-demethylation of tramadol, but is not involved in N-demethylation. "	( Post-mortem SNP analysis of CYP2D6 gene reveals correlation between genotype and opioid drug (tramadol) metabolite ratios in blood. Koski, A; Levo, A; Ojanperä, I; Sajantila, A; Vuori, E, 2003)	1.98
"Tramadol is a centrally acting analgesic used for prevention and treatment of moderate to severe pain. "	( HPLC determination of tramadol in human breast milk. Kmetec, V; Roskar, R, 2003)	2.08
"Tramadol is a centrally acting synthetic analgesic with mu-opioid receptor agonist activity, it is a widely prescribed analgesic used in the treatment of moderate to severe pain and as an alternative to opiates. "	( Determination of tramadol in hair using solid phase extraction and GC-MS. Abu-Ragheib, S; Al-Nsour, T; Almasad, JK; Hadidi, KA, 2003)	2.1
"Tramadol is an important spinal drug which produces analgesia following intrathecal injection. "	( Effect of the spinal drug tramadol on the fatty acid compositions of rabbit spinal cord and brain. Alici, HA; Cesur, M; Ozmen, I; Sahin, F, 2003)	2.06
"Tramadol hydrochloride is an analgesic with mixed -mu and non-opioid activities which has less respiratory depression effects compared to morphine."	( Recovery following tonsillectomy a comparison between tramadol and morphine for analgesia. Chew, ST; Ip-Yam, PC; Kong, CF, 2003)	1.29
"Tramadol is a centrally acting synthetic analgesic agent with opiate activity due to low affinity binding of the parent compound and higher affinity binding of the O-demethylated metabolite M1 to mu opioid receptors."	( Tramadol versus buprenorphine for the treatment of opiate withdrawal: a retrospective cohort control study. Brateanu, A; Heggi, A; Parran, TV; Rabb, M; Tamaskar, R; Yu, J, 2003)	2.48
"Tramadol is a multimodal analgesic with proven dose-related efficacy over a variety of perioperative surgical fields and is efficacious in treating both neuropathic and cancer pain. "	( Tramadol--a multimodal, multipurpose analgesic for the surgeon. Shipton, EA, 2003)	3.2
"Tramadol is a weak opioid agonist with antinociceptive effects through its action on the mu-receptor and by inhibiting the neuronal re-uptake of both noradrenaline and serotonin. "	( Two doses of oral sustained-release tramadol do not reduce pain or morphine consumption after modified radical mastectomy: a randomized, double blind, placebo-controlled trial. Klaichanad, C; Krisanaprakornkit, W; Taesiri, W; Thaninsurat, N; Thienthong, S; Utsahapanich, S, 2004)	2.04
"Tramadol is an effective treatment for neuropathic pain."	( Tramadol for neuropathic pain. Cornblath, DD; Duhmke, RM; Hollingshead, JR, 2004)	3.21
"Tramadol is an analgesic and antitussive agent that is metabolized to O-desmethyltramadol (M1), which is also active. "	( Pharmacokinetics of tramadol and the metabolite O-desmethyltramadol in dogs. KuKanich, B; Papich, MG, 2004)	2.09
"Tramadol is a centrally acting analgesic that demonstrates opioid and monoaminergic properties. "	( Antidepressant-like effect of tramadol and its enantiomers in reserpinized mice: comparative study with desipramine, fluvoxamine, venlafaxine and opiates. Berrocoso, E; Gibert-Rahola, J; Micó, JA; Rojas-Corrales, MO, 2004)	2.05
"Tramadol is a centrally acting analgesic with weak opioid agonist properties, which also has monoaminergic activity, exerted via inhibition of neuronal uptake of serotonin and norepinephrine. "	( The xerogenic potency and mechanism of action of tramadol inhibition of salivary secretion in rats. Götrick, B; Tobin, G, 2004)	2.02
"Tramadol is an atypical opioid with a complex mechanism of action including the synergistic interaction between the parent drug and an active metabolite. "	( Evidence of self-synergism in the antinociceptive effect of tramadol in rats. Aguirre-Bañuelos, P; Arellano-Guerrero, A; de Pozos-Guillén, AJ; Hoyo-Vadillo, C; Pérez-Urizar, J, 2004)	2.01
"Tramadol is an opioid acting on mu-receptors and the monoaminergic pain modulating systems."	( Reducing cardiovascular responses to laryngoscopy and tracheal intubation: a comparison of equipotent doses of tramadol, nalbuphine and pethidine, with placebo. Baloch, M; Halliday, EM; Rasheed, A; Soomro, NA; van den Berg, AA, 2004)	1.26
"Tramadol is a centrally-acting analgesic drug. "	( The median effective dose of tramadol and morphine for postoperative patients: a study of interactions. Benhamou, D; Marcou, TA; Marque, S; Mazoit, JX, 2005)	2.06
"Tramadol is a synthetic analgesic new to the Australasian market where its use is rapidly increasing. "	( Tramadol: does it have a role in emergency medicine? Close, BR, 2005)	3.21
"Tramadol hydrochloride is a centrally acting analgesic, which possesses opioid agonist properties and activates monoaminergic spinal inhibition of pain. "	( Long-term tolerability of tramadol LP, a new once-daily formulation, in patients with osteoarthritis or low back pain. Coffiner, M; Fontaine, D; Malonne, H; Peretz, A; Sereno, A; Sonet, B; Vanderbist, F, 2005)	2.07
"Tramadol is a synthetic opioid that has been available in the Netherlands since 1992 and is usually used as a centrally-acting analgesic when paracetamol or an NSAID provides insufficient relief. "	( [Side effects of tramadol: 12 years of experience in the Netherlands]. Kabel, JS; van Puijenbroek, EP, 2005)	2.11
"Tramadol is a unique analgesic that has been associated with seizures on overdose."	( Tramadol exposures reported to statewide poison control system. Albertson, TE; Alsop, JA; Marquardt, KA, 2005)	3.21
"Tramadol is a mu opioid agonist that also inhibits the reuptake of norepinephrine and serotonin. "	( Profiling the subjective, psychomotor, and physiological effects of tramadol in recreational drug users. Zacny, JP, 2005)	2.01
"Tramadol is a centrally acting analgesic drug used mainly in the moderate to severe pain control. "	( Tramadol-induced blockade of delayed rectifier potassium current in NG108-15 neuronal cells. Liu, YC; Tsai, TY; Tsai, YC; Wu, SN, 2006)	3.22
"Tramadol is an alternative to other opioids for postoperative pain management. "	( Comparison of morphine and tramadol by patient-controlled analgesia for postoperative analgesia after tonsillectomy in children. Güneş, Y; Ozalevli, M; Ozcengiz, D; Tuncer, U; Unlügenç, H, 2005)	2.07
"Tramadol is a centrally acting opioid analgesic structurally related to codeine and morphine. "	( Derivatives of tramadol for increased duration of effect. Abolin, C; Hewitt, MC; Koch, P; Shao, L; Varney, M, 2006)	2.13
"Tramadol is a weak opioid agonist and an inhibitor of the reuptake of noradrenaline and serotonin. "	( Ondansetron does not block tramadol-induced analgesia in mice. Erhan, E; Kocabas, S; Kosay, S; Onal, A; Parlar, A; Yegul, I, 2005)	2.07
"Tramadol is an analgesic with micro-opioid and nonopioid activity."	( Tramadol for pain relief in children undergoing herniotomy: a comparison with ilioinguinal and iliohypogastric blocks. Azemati, S; Khezri, S; Khosravi, MB, 2006)	2.5
"Tramadol is a synthetic, centrally acting analgesic. "	( Tramadol sustained-release capsules. Keating, GM, 2006)	3.22
"Tramadol is a centrally acting synthetic analgesic with opiate activity primarily due to the binding of a metabolite to the micro receptor."	( Tramadol versus buprenorphine for the management of acute heroin withdrawal: a retrospective matched cohort controlled study. Adelman, CA; Grey, SF; Parran, TV; Threlkeld, M; Yu, J, )	2.3
"Tramadol is a centrally-acting analgesic endowed with opioid, noradrenergic and serotonergic properties. "	( In vivo effect of tramadol on locus coeruleus neurons is mediated by alpha2-adrenoceptors and modulated by serotonin. Berrocoso, E; Micó, JA; Ugedo, L, 2006)	2.11
"Tramadol ER is a useful treatment option for patients with osteoarthritis pain."	( Extended-release tramadol in the treatment of osteoarthritis: a multicenter, randomized, double-blind, placebo-controlled clinical trial. Fleming, RR; Gana, TJ; Janagap, CC; Pascual, ML; Schein, JR; Vorsanger, GJ; Xiang, J, 2006)	1.39
"Tramadol is an effective treatment for neuropathic pain."	( Tramadol for neuropathic pain. Cornblath, DR; Dühmke, RM; Hollingshead, J, 2006)	3.22
"Tramadol is an atypical opioid with a complex mechanism of action including a synergistic interaction between the parent drug and an active metabolite. "	( Isobolographic analysis of the dual-site synergism in the antinociceptive response of tramadol in the formalin test in rats. Aguirre-Bañuelos, P; Arellano-Guerrero, A; Castañeda-Hernández, G; Hoyo-Vadillo, C; Pérez-Urizar, J; Pozos-Guillén, AJ, 2006)	2
"Tramadol is a centrally acting analgesic used to treat many pain disorders."	( Combination of oral tramadol, acetaminophen and 1% lidocaine induced periprostatic nerve block for pain control during transrectal ultrasound guided biopsy of the prostate: a prospective, randomized, controlled trial. Carvin, DM; Costa, J; Pendleton, J; Rosser, CJ; Wludyka, P, 2006)	1.38
"Tramadol is a commonly used synthetic opioid with the advantage of lowering the potential for dependence. "	( Successful anticoagulation and continuation of tramadol therapy in the setting of a tramadol-warfarin interaction. Dumo, PA; Kielbasa, LA, 2006)	2.03
"Tramadol is a synthetic, centrally acting opioid analgesic. "	( Tramadol extended-release tablets. Curran, MP; Hair, PI; Keam, SJ, 2006)	3.22
"Tramadol is a therapeutic option for the control of neuropathic pain in patients with cancer, and appears to improve quality of life in these patients. "	( Tramadol in the treatment of neuropathic cancer pain: a double-blind, placebo-controlled study. Arbaiza, D; Vidal, O, 2007)	3.23
"Tramadol is an extensively used centrally acting analgesic and is considered a safe drug devoid of many serious adverse effects of traditional opioids. "	( Fatal unintentional intoxications with tramadol during 1995-2005. Ahlner, J; Hägg, S; Jönsson, AK; Tjäderborn, M, 2007)	2.05
"Tramadol is an analgesic that is used worldwide, but its mechanisms of action have not been elucidated. "	( Pharmacological aspects of the effects of tramadol on G-protein coupled receptors. Minami, K; Ueta, Y; Uezono, Y, 2007)	2.05
"Tramadol is a racemic mixture of 2 enantiomers that have comparable pharmacokinetic profile and this lack of difference is also observed with their main active metabolite, O-demethyl tramadol (M1)."	( [Pharmacokinetics of tramadol in children]. Habre, W; Saudan, S, 2007)	1.38
"Tramadol is a good alternative to NSAIDs and to morphine for moderate pain but its efficacy is variable due to the genetic polymorphism of its metabolism and possible drug interactions."	( [Tramadol for acute postoperative pain in children]. Pendeville, PE; Veyckemans, F, 2007)	1.97
"Tramadol is a synthetic analog of codeine with opioid and local anesthetic properties. "	( The antibacterial activity of tramadol against bacteria associated with infectious complications after local or regional anesthesia. Bonnaure-Mallet, M; Donnio, PY; Jolivet-Gougeon, A; Repère, M; Shacoori, V; Tamanai-Shacoori, Z; Vo Van, JM, 2007)	2.07
"Tramadol ER* is a once-daily oral analgesic for management of moderate-to-moderately severe chronic pain in adults who require around-the-clock treatment of pain. "	( Open-label study of the safety and effectiveness of long-term therapy with extended-release tramadol in the management of chronic nonmalignant pain. Fleming, RR; Gana, TJ; Pascual, ML; Vorsanger, GJ, 2007)	2
"Tramadol is reported to be an effective analgesic."	( Peritonsillar infiltration with tramadol improves pediatric tonsillectomy pain. Atef, A; Fawaz, AA, 2008)	1.35
"Tramadol is an atypical analgesic with a unique dual mechanism of action. "	( The novel compound (+/-)-1-[10-((E)-3-Phenyl-allyl)-3,10-diaza-bicyclo[4.3.1]dec-3-yl]-propan-1-one (NS7051) attenuates nociceptive transmission in animal models of experimental pain; a pharmacological comparison with the combined mu-opioid receptor agoni Baek, CA; Erichsen, HK; Munro, G; Nielsen, AN; Nielsen, EØ; Peters, D; Scheel-Kruger, J; Weikop, P, 2008)	1.79
"Tramadol is a centrally acting, synthetic analgesic. "	( Tramadol extended-release formulations in the management of pain due to osteoarthritis. Mongin, G, 2007)	3.23
"Tramadol is an analgesic agent and is used in dogs and cats. "	( Pharmacokinetics of tramadol, and its metabolite O-desmethyl-tramadol, in cats. Ilkiw, JE; Pypendop, BH, 2008)	2.11
"Tramadol is a centrally acting analgesic drug that has been used clinically for the last two decades to treat moderate to moderately severe pain in humans. "	( Pharmacokinetics of tramadol in horses after intravenous, intramuscular and oral administration. Britzi, M; Eytan, B; Lifschitz, T; Shilo, Y; Soback, S; Steinman, A, 2008)	2.11
"Tramadol is a centrally acting opioid analgesic structurally related to codeine and morphine. "	( In vitro and in vivo evaluation of O-alkyl derivatives of tramadol. Bakale, R; Bhongle, N; Currie, M; Fang, K; Grover, P; Hewitt, M; Jerussi, TP; Koch, P; Malcolm, S; Ribe, S; Senanayake, C; Shao, L; Wu, F, 2008)	2.03
"Tramadol is a centrally acting analgesic in widespread use throughout the world. "	( Basic pharmacology relevant to drug abuse assessment: tramadol as example. Raffa, RB, 2008)	2.04
"Tramadol is a centrally acting synthetic opioid analgesic that has a dual mechanism of action, binding to mu-opioid receptors and weakly inhibiting the neuronal reuptake of norepinephrine and serotonin. "	( Extended-release Tramadol (ULTRAM ER): a pharmacotherapeutic, pharmacokinetic, and pharmacodynamic focus on effectiveness and safety in patients with chronic/persistent pain. Barkin, RL, )	1.91
"Tramadol is an effective analgesic substance widely used in medical practice. "	( The analgesic drug, tramadol, acts as an agonist of the transient receptor potential vanilloid-1. Bíró, T; Czifra, G; Kovács, L; Marincsák, R; Szabó, T; Tóth, BI, 2008)	2.11
"Tramadol (Tramal) is a new analgetic drug without side effects: no postnarcotic respiratory depression, sickness or vomiting do not occur, and it does not interfere with the cardiovascular system."	( [Infusion-controlled Tramal-anaesthesia (author's transl)]. Stoffregen, J, 1980)	0.98
"Tramadol hydrochloride is a synthetic mu-opioid agonist with additional monoaminergic activity. "	( Lack of analgesic effect of 50 and 100 mg oral tramadol after orthopaedic surgery: a randomized, double-blind, placebo and standard active drug comparison. Breivik, H; Grimstad, J; Stubhaug, A, 1995)	1.99
"Tramadol is a weak opioid analgesic with a potency comparable to that of pethidine."	( Tramadol for the management of acute pain. Lehmann, KA, 1994)	2.45
"Tramadol is a centrally acting analgesic which possesses opioid agonist properties and activates monoaminergic spinal inhibition of pain. "	( Tramadol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in acute and chronic pain states. Lee, CR; McTavish, D; Sorkin, EM, 1993)	3.17
"Tramadol is a centrally acting analgesic with low affinity to opioid receptors. "	( Inhibition of spinal noradrenaline uptake in rats by the centrally acting analgesic tramadol. Hennies, HH; Reimann, W, 1994)	1.96
"1. Tramadol is a centrally acting analgesic with low opioid receptor affinity and, therefore, presumably additional mechanisms of analgesic action. "	( Effects of the central analgesic tramadol and its main metabolite, O-desmethyltramadol, on rat locus coeruleus neurones. Driessen, B; Illes, P; Nieber, K; Sevcik, J, 1993)	1.19
"Tramadol is a central analgesic with low affinity for opioid receptors. "	( [Duality of the analgesic effect of tramadol in humans]. Collart, L; Dayer, P; Favario-Constantin, C; Luthy, C, 1993)	2
"Tramadol is a good alternative for Naproxen at outpatient VABRA or HSG procedures when Naproxen is contra-indicated."	( Pain relief during and following outpatient curettage and hysterosalpingography: a double blind study to compare the efficacy and safety of tramadol versus naproxen. Cobra Research Group. Damen, AC; Drogendijk, AC; Holm, JP; Peters, AA; Trimbos, JB; vd Velde, EA; Witte, EH, 1996)	1.94
"Tramadol is a weak opioid with effects on adrenergic and serotonergic neurotransmission that is used to treat cancer pain and chronic non malignant pain. "	( Nightmares and hallucinations after long-term intake of tramadol combined with antidepressants. De Laat, M; Devulder, J; Dumoulin, K; Renson, A; Rolly, G, 1996)	1.98
"Tramadol is a cyclohexanol derivative with mu-agonist activity. "	( A risk-benefit assessment of tramadol in the management of pain. Grond, S; Lehmann, KA; Radbruch, L, 1996)	2.03
"Tramadol is a centrally acting analgesic that has been shown to be effective in a variety of acute and chronic pain states. "	( Pharmacology and clinical experience with tramadol in osteoarthritis. Katz, WA, 1996)	2
"Tramadol hydrochloride is a centrally acting synthetic analgesic in widespread clinical use. "	( Tramadol, M1 metabolite and enantiomer affinities for cloned human opioid receptors expressed in transfected HN9.10 neuroblastoma cells. Lai, J; Ma, SW; Porreca, F; Raffa, RB, 1996)	3.18
"Tramadol is a synthetic analogue of codeine that binds to mu opiate receptors and inhibits norepinephrine and serotonin reuptake."	( Tramadol: a new centrally acting analgesic. Han, NH; Lewis, KS, 1997)	2.46
"Tramadol is an alkaline extractable drug and elutes from a HP-5 column without the need for derivatization."	( Tramadol distribution in four postmortem cases. Levine, B; Ramcharitar, V; Smialek, JE, 1997)	2.46
"Tramadol is a synthetic, centrally acting analgesic with both opioid and nonopioid analgesic activity."	( [Treatment of post-herpes zoster pain with tramadol. Results of an open pilot study versus clomipramine with or without levomepromazine]. Göbel, H; Stadler, T, 1997)	1.28
"Tramadol is a new, centrally acting analgesic with a dual mechanism of action."	( [Effectiveness and tolerance of tramadol in cancer pain. A comparative study with respect to buprenorphine]. Bono, AV; Cuffari, S, 1997)	1.3
"Tramadol is a novel analgesic possessing both opiate and noradrenergic effects. "	( Prospective multicenter evaluation of tramadol exposure. Anderson, DL; Benson, BE; Gorman, SE; Ruskosky, DR; Spiller, HA; Stancavage, MM; Villalobos, D, 1997)	2.01
"Tramadol is an effective analgesic that works through a combined mechanism of weak mu receptor binding and the inhibition of serotonin and norepinephrine reuptake."	( Nonsteroidal anti-inflammatory drugs, traditional opioids, and tramadol: contrasting therapies for the treatment of chronic pain. Aronson, MD, )	1.09
"Tramadol is a centrally acting analgesic drug; it has an agonist effect on mu 1 receptors of opioids and acts also by inhibiting the re-uptake of noradrenaline and serotonine which activates descending monoaminergic inhibitory pathways."	( [Treatment of pain in oncology]. De Conno, F; Polastri, D, 1997)	1.02
"Tramadol (Ultram) is a new analgesic agent with a dual mechanism of action that includes weak agonistic effects at the mu-opioid receptor as well as inhibition of neurotransmitter (serotonin, norepinephrine) re-uptake. "	( Seizure after overdose of tramadol. Tobias, JD, 1997)	2.04
"Tramadol is a centrally acting analgesic drug with a dual mechanism of action: binding to mu-opioid receptors and potentiation of the monoaminergic systems. "	( Effects of tramadol on immune responses and nociceptive thresholds in mice. Bianchi, M; Manfredi, B; Panerai, AE; Sacerdote, P, 1997)	2.13
"1. Tramadol hydrochloride is a centrally acting opioid analgesic, the efficacy and potency of which is only five to ten times lower than that of morphine. "	( Effect of acute and chronic tramadol on [3H]-5-HT uptake in rat cortical synaptosomes. Buriani, A; Cima, L; Giusti, P; Lipartiti, M, 1997)	1.21
"Tramadol is an atypical centrally acting analgesic agent with relatively weak opioid receptor affinity in comparison with its antinociceptive efficacy. "	( Actions of tramadol, its enantiomers and principal metabolite, O-desmethyltramadol, on serotonin (5-HT) efflux and uptake in the rat dorsal raphe nucleus. Bamigbade, TA; Davidson, C; Langford, RM; Stamford, JA, 1997)	2.13
"Tramadol is a centrally acting, binary analgesic that is neither an opiate-derived nor a nonsteroidal anti-inflammatory drug and that was approved for use in the United States in 1995. "	( Identification of tramadol and its metabolites in blood from drug-related deaths and drug-impaired drivers. Christian, GD; Goeringer, KE; Logan, BK, )	1.91
"Tramadol is a centrally acting opioid with a low affinity for mu-opioid receptors, which has been claimed not to depress respiration as do the classic opioids. "	( Comparison of respiratory effects of tramadol and pethidine. Lindgren, L; Tarkkila, P; Tuominen, M, 1998)	2.02
"Tramadol is an analgesic with combined opioid agonist and monoamine reuptake blocker properties, which may be useful as a perioperative analgesic and antinociceptive adjuvant."	( Preoperative adjuvant epidural tramadol: the effect of different doses on postoperative analgesia and pain processing. Farschtschian, M; Naji, P; Wilder-Smith, CH; Wilder-Smith, OH, 1998)	2.03
"Tramadol is an effective analgesic agent for the relief of acute postoperative pain when administered by PCA via the subcutaneous route. "	( Comparison of tramadol and morphine via subcutaneous PCA following major orthopaedic surgery. Boon, J; De Wet, C; Hopkins, D; Murphy, J; Potgieter, D; Shipton, EA; Van derMerwe, CA, 1998)	2.1
"Tramadol is a centrally acting analgesic for use in treating moderate to moderately severe pain."	( Double-blind randomized trial of tramadol for the treatment of the pain of diabetic neuropathy. Cornblath, D; Donofrio, P; Edelman, S; Gooch, C; Greene, D; Harati, Y; Kamin, M; Raskin, P; Sachdeo, R; Siu, CO; Swenson, M, 1998)	1.3
"Tramadol hydrochloride is a novel, centrally acting analgesic with two complementary mechanisms of action: opioid and aminergic. "	( Tramadol hydrochloride: analgesic efficacy compared with codeine, aspirin with codeine, and placebo after dental extraction. Bakos, L; Crout, RJ; Graves, RW; Jackson, DL; Moore, PA; Schneider, LG, 1998)	3.19
"Tramadol is a centrally acting analgesic."	( The experimental toxicology of tramadol: an overview. Coogan, TP; Matthiesen, T; Uragg, H; Wöhrmann, T, 1998)	1.31
"Tramadol is a centrally acting analgesic with several modes of action. "	( Induction of 5-hydroxytryptamine release by tramadol, fenfluramine and reserpine. Reimann, W; Schneider, F, 1998)	2
"Tramadol is a clinically-effective, centrally-acting analgesic. "	( Tramadol induces antidepressant-type effects in mice. Gibert-Rahola, J; Micó, JA; Rojas-Corrales, MO, 1998)	3.19
"Tramadol is a central-acting analgesic."	( Local anesthetic effect of tramadol, metoclopramide, and lidocaine following intradermal injection. Chang, DP; Huang, MH; Mok, MS; Pang, WW, )	1.15
"Tramadol is a central-acting analgesic."	( Intradermal injection of tramadol has local anesthetic effect: a comparison with lidocaine. Chang, DP; Huang, MH; Lin, CH; Mok, MS; Pang, WW; Yang, TF, 1998)	1.32
"Tramadol is an analgesic drug that is antagonized by alpha2-adrenoceptor antagonists, as well as opioid antagonists. "	( Tramadol added to mepivacaine prolongs the duration of an axillary brachial plexus blockade. Gollmann, G; Kapral, S; Lehofer, F; Likar, R; Sladen, RN; Waltl, B; Weinstabl, C, 1999)	3.19
"Tramadol (Ultram) is a centrally acting, synthetic analgesic agent. "	( Tissue distribution of tramadol and metabolites in an overdose fatality. Cina, SJ; Jones, R; Levine, B; Moore, KA; Selby, DM; Smith, ML, 1999)	2.06
"Tramadol is a central analgesic that seems to have fewer side effects and a lower abuse potential than classical opioids. "	( Treatment of restless legs syndrome with tramadol: an open study. Lauerma, H; Markkula, J, 1999)	2.01
"Tramadol is a centrally acting opioid analgesic whose mechanism of action could also involve an increase in central serotoninergic transmission. "	( Release studies with rat brain cortical synaptosomes indicate that tramadol is a 5-hydroxytryptamine uptake blocker and not a 5-hydroxytryptamine releaser. Gobbi, M; Mennini, T, 1999)	1.98
"1 Tramadol hydrochloride is a centrally acting opioid analgesic whose efficacy and potency is only five to ten times lower than that of morphine. "	( Effect of acute and chronic tramadol on [3H]-norepinephrine-uptake in rat cortical synaptosomes. Franceschini, D; Giusti, P; Lipartiti, M, 1999)	1.32
"Tramadol hydrochloride is a novel, centrally acting analgesic with two complementary mechanisms of action: opioid and aminergic. "	( Pain management in dental practice: tramadol vs. codeine combinations. Moore, PA, 1999)	2.02
"Tramadol is a synthetic analog of codeine with a dual mechanism of action that involves agonist activity at the mu opioid receptor, as well as inhibition of monoaminergic (norepinephrine and serotonin) re-uptake."	( Analgesics in ophthalmic practice: a review of the oral non-narcotic agent tramadol. Barkin, RL; Gaynes, BI, 1999)	1.25
"Tramadol is an analgesic drug acting directly on opioid receptors and indirectly on monoaminergic receptor systems."	( Tramadol relieves pain and allodynia in polyneuropathy: a randomised, double-blind, controlled trial. Andersen, G; Brøsen, K; Jensen, TS; Madsen, C; Sindrup, SH; Smith, T, 1999)	2.47
"Tramadol is a racemic drug that may act through a monoaminergic effect of (+)- and (-)-tramadol and through an opioid effect of its metabolite (+)-Ml. "	( The effect of tramadol in painful polyneuropathy in relation to serum drug and metabolite levels. Brøsen, K; Jensen, TS; Madsen, C; Sindrup, SH, 1999)	2.11
"Tramadol is a novel central acting analgesic. "	( The effects of tramadol versus fentanyl in attenuating hemodynamic response following tracheal intubation. Chang, DP; Huang, MH; Lei, CH; Pang, WW; Tung, CC, 1999)	2.1
"Tramadol is a mixture of stereoisomers."	( Effects of tramadol stereoisomers on norepinephrine efflux and uptake in the rat locus coeruleus measured by real time voltammetry. Bamigbade, TA; Callado, LF; Halfpenny, DM; Hopwood, SE; Langford, RM; Stamford, JA, 1999)	1.41
"Tramadol is a synthetic, centrally acting analgesic agent with 2 distinct, synergistic mechanisms of action, acting as both a weak opioid agonist and an inhibitor of monoamine neurotransmitter reuptake. "	( Tramadol: a review of its use in perioperative pain. Perry, CM; Scott, LJ, 2000)	3.19
"Tramadol is a weak centrally acting analgesic and it might provide efficacious postoperative pain relief with minimal sedative effects in the use of intravenous patient-controlled analgesia (PCA). "	( Comparison of intravenous patient-controlled analgesia with tramadol versus morphine after microvascular breast reconstruction. Pitkänen, M; Rosenberg, PH; Silvasti, M; Svartling, N, 2000)	1.99
"Tramadol hydrochloride is a centrally acting analgesic with a partial affinity for the opiate receptor (mu), having an analgesic potency estimated to be one tenth that of morphine. "	( Methadone detoxification of tramadol dependence. DeGuiseppe, B; Leo, RJ; Narendran, R, 2000)	2.04
"Tramadol is a centrally acting opioid-like analgesic commonly used for analgesia during surgery. "	( Effect of tramadol on electroencephalographic and auditory-evoked response variables during light anaesthesia. Brunner, MD; Shinner, G; Thornton, C; Vaughan, DJ, 2000)	2.15
"Tramadol is an option for the treatment of rheumatological pain. "	( The tramadol option. Desmeules, JA, 2000)	2.31
"Tramadol is an inhibitor of the re-uptake of serotonin (5-hydroxytryptamine) and norepinephrine in the spinal cord."	( Tramadol for postoperative shivering: a double-blind comparison with pethidine. Bhatnagar, S; Kannan, TR; Mishra, S; Panigrahi, M; Punj, J; Saxena, A, 2001)	2.47
"Tramadol is an acceptable alternative to morphine in the prehospital trauma setting."	( Tramadol, an alternative to morphine for treating posttraumatic pain in the prehospital situation. Degesves, S; Garcet, L; Magotteaux, V; Vergnion, M, 2001)	2.47
"Tramadol is an analgesic assumed to lack a respiratory depressant effect and has been shown to provide effective, long-lasting analgesia after epidural administration in adults and children."	( Caudal bupivacaine-tramadol combination for postoperative analgesia in pediatric herniorrhaphy. Akyol, A; Dohman, D; Senel, AC; Solak, M, 2001)	1.36
"Tramadol hydrochloride is a centrally-acting, synthetic analgesic with a dual mechanism of action-weak opioid and monoaminergic effects. "	( [Tramadol in the treatment of pain]. Curković, B, 2000)	2.66
"Tramadol is a widely used, centrally acting analgesic, but its mechanisms of action are not completely understood. "	( Inhibition by tramadol of muscarinic receptor-induced responses in cultured adrenal medullary cells and in Xenopus laevis oocytes expressing cloned M1 receptors. Minami, K; Shigematsu, A; Shiraishi, M; Uezono, Y; Yanagihara, N, 2001)	2.11
"Tramadol is a synthetic analgesic that has been shown to be effective both alone and in combination with APAP."	( Tramadol/acetaminophen combination tablets and codeine/acetaminophen combination capsules for the management of chronic pain: a comparative trial. Lacy, JR; Mullican, WS, 2001)	2.47
"Tramadol hydrochloride is a racemic mixture of two enantiomers. "	( Tramadol drops in children: analgesic efficacy, lack of respiratory effects, and normal recovery times. Payne, KA; Roelofse, JA, 1999)	3.19
"Tramadol is an analgesic that inhibits norepinephrine (NE) reuptake. "	( Tramadol has no effect on cortical renal blood flow--despite increased serum catecholamine levels--in anesthetized rats: implications for analgesia in renal insufficiency. Aoyama, K; Minami, K; Nagaoka, E; Shiga, Y; Shigematsu, A; Shiraishi, M; Uezono, Y, 2002)	3.2
"Tramadol is a widely used analgesic, but its mode of action is not well understood. "	( Tramadol inhibits norepinephrine transporter function at desipramine-binding sites in cultured bovine adrenal medullary cells. Minami, K; Sagata, K; Shigematsu, A; Shiraishi, M; Toyohira, Y; Ueno, S; Yanagihara, N, 2002)	3.2
"Tramadol hydrochloride is a synthetic opiate agonist with a plasma elimination half-life of 5 to 6 hours and peak plasma levels at about 1 1/2 hours. "	( Analgesic oral efficacy of tramadol hydrochloride in postoperative pain. DeCastro, A; Minn, FL; Olson, NZ; Sunshine, A; Zighelboim, I, 1992)	2.02
"1. Tramadol is a centrally acting analgesic with low opioid receptor affinity and therefore presumably other mechanisms of analgesic action. "	( Interaction of the central analgesic, tramadol, with the uptake and release of 5-hydroxytryptamine in the rat brain in vitro. Driessen, B; Reimann, W, 1992)	1.18
"tramadol boluses is a safe and recommended mode of post-operative intravenous pain therapy."	( Intravenous tramadol for post-operative pain--comparison of intermittent dose regimens with and without maintenance infusion. Alon, E; Atanassoff, P; Buzina, M; Chrubasik, J; Schulte-Mönting, J, 1992)	1.38

Excerpt	Reference	Relevance
"Tramadol has a more negative impact on the locomotor parameters compared with pregabalin."	( Comparative Study of the Neurotoxic Effects of Pregabalin Versus Tramadol in Rats. El Bakary, AA; El-Kattan, MA; Elsukary, AE; Helaly, AMNZ; Moustafa, ME, 2022)	1.68
"Tramadol has a higher risk of fractures than some other opioid analgesics used to treat moderate-to-severe pain and, in the model described here, we investigate the cost effectiveness of transdermal buprenorphine treatment compared with tramadol in a high-risk population."	( Tramadol and the risk of fracture in an elderly female population: a cost utility assessment with comparison to transdermal buprenorphine. Akehurst, R; Dunlop, W; Hirst, A; Hirst, M; Knight, C, 2016)	2.6
"Tramadol has an important position as a Step II agent on the WHO pain ladder, where it is effective for a variety of syndromes in patients with mild to moderate pain intensity. "	( Tramadol in palliative care #290. Arnold, RM; Pruskowski, J, 2015)	3.3
"Tramadol has a brief local anesthetic-like action when administered to ulnar nerve perineurally."	( Effects of perineural tramadol on sensory and motor conduction of ulnar nerve. Beyazova, M; Gökyar, I; Kaya, K; Oztürk, E; Sezer, OA; Zinnuroğlu, M, )	1.89
"Tramadol has a better analgesic effect in third molar surgery than fentanyl and placebo."	( A comparison of the effects of midazolam/fentanyl and midazolam/tramadol for conscious intravenous sedation during third molar extraction. Garip, H; Göker, K; Göktay, O; Gönül, O; Satilmiş, T, 2011)	2.05
"Tramadol has a dual mechanism of action: weak mu opioid receptor agonist and a reuptake inhibitor of serotonin and noradrenaline."	( Tramadol: does it have a role in emergency medicine? Close, BR, 2005)	2.49
"Tramadol has a minor delaying effect on colonic transit, but no effect on upper gastrointestinal transit or gut smooth muscle tone. "	( The analgesic tramadol has minimal effect on gastrointestinal motor function. Bettiga, A; Wilder-Smith, CH, 1997)	2.1
"Tramadol has a favorable adverse-effect profile and therefore is likely to have an important role in the management of chronic pain syndromes."	( Nonsteroidal anti-inflammatory drugs, traditional opioids, and tramadol: contrasting therapies for the treatment of chronic pain. Aronson, MD, )	1.09
"Tramadol also has a low potential for abuse or dependence."	( Tramadol: a review of its use in perioperative pain. Perry, CM; Scott, LJ, 2000)	2.47
"Tramadol has a dual mechanism of action that includes weak agonistic effects at the mu-opioid receptor as well as inhibition of monoamine (serotonin, norepinephrine) re-uptake."	( Anticonvulsant and proconvulsant effects of tramadol, its enantiomers and its M1 metabolite in the rat kindling model of epilepsy. Friderichs, E; Löscher, W; Potschka, H, 2000)	1.29
"Tramadol has uncertain efficacy and a concerning adverse effect profile compared with traditional opioids."	( Tramadol Use in United States Emergency Departments 2007-2018. Mazer-Amirshahi, M; Mullins, PM; Nelson, LS; Perrone, J; Pines, JM; Pourmand, A, 2022)	2.89
"Tramadol has extracted from the exhaled breath condensate (EBC) samples through the supported liquid membrane consisting of 2-nitrophenyl octyl ether impregnated in the hollow fiber wall, and the lumen of the hollow fiber was filled with 20 μL of an acceptor phase. "	( Electromembrane extraction of tramadol from exhaled breath condensate and its liquid chromatographic analysis. Hoseininezhad-Namin, MS; Jouyban, A; Jouyban-Gharamaleki, V; Khoubnasabjafari, M; Ozkan, SA; Rahimpour, E; Seyfinejad, B; Soleymani, J, 2022)	2.45
"Tramadol has a more negative impact on the locomotor parameters compared with pregabalin."	( Comparative Study of the Neurotoxic Effects of Pregabalin Versus Tramadol in Rats. El Bakary, AA; El-Kattan, MA; Elsukary, AE; Helaly, AMNZ; Moustafa, ME, 2022)	1.68
"Tramadol has been used by millions of patients as an analgesic drug to relief the severe pain caused by cancers and other diseases. "	( Antioxidants (selenium and garlic) alleviated the adverse effects of tramadol on the reproductive system and oxidative stress markers in male rabbits. El-Dafrawi, YA; El-Ghalid, OA; Ghoneim, AA; Sheweita, SA; Wahid, A, 2022)	2.4
"Tramadol has been proven to reduce pain effectively."	( Influence of tramadol on bacterial burden in the standard neutropenic thigh infection model. Rox, K, 2022)	1.81
"Tramadol has been linked to abuse in recent clinical investigations."	( Reinforcing effect of tramadol in the rat. Hafidi, A; Hamdi, D; Lashin, M; Omara-Reda, H; Ouachikh, O, 2023)	1.95
"Tramadol has been reported to cause hyponatremia but the evidence is conflicting. "	( Risk of Hyponatremia after Tramadol/Acetaminophen Single-Pill Combination Therapy: A Real-World Study Based on the OMOP-CDM Database. Choi, B; Han, Y; Hwang, K; Kim, IY; Kim, J; Lee, YJ; Oh, TR; Rhee, H, 2023)	2.65
"Tramadol has been widely used among patients with osteoarthritis (OA); however, there is paucity of information on its cardiovascular risk. "	( Association of tramadol with risk of myocardial infarction among patients with osteoarthritis. Choi, HK; Dubreuil, M; LaRochelle, MR; Lei, G; Lin, J; Lu, N; Tomasson, G; Wei, J; Wood, MJ; Zeng, C; Zhang, Y, 2020)	2.35
"Tramadol-induced mania has been described with selective serotonin reuptake inhibitors but not SNRIs."	( Mania induced by tramadol-venlafaxine combination. Ahmed, A; Grekin, J; Hefzi, N, )	1.19
"Tramadol has been recommended for management of osteoarthritis-related pain; however, outcomes following total hip arthroplasty (THA) in patients taking tramadol in the preoperative period have not been well described."	( Preoperative Pain Management: Is Tramadol a Safe Alternative to Traditional Opioids Before Total Hip Arthroplasty? Bell, JE; Browne, JA; Chen, DQ; Haug, EC; Sequeira, SB; Werner, BC, 2020)	1.56
"Tramadol abuse has become a crisis in Egypt and many other Middle Eastern countries. "	( Free Testosterone and Prolactin Levels and Sperm Morphology and Function Among Male Patients With Tramadol Abuse: A Case-Control Study. Bassiony, MM; El-Gohari, H; Youssef, UM, )	1.79
"Oral tramadol has been ap-proved in the United States since 1995 and intravenous (IV) tramadol has been widely prescribed outside the United States (OUS); nevertheless, IV tramadol has not yet been approved for use in the United States."	( IV tramadol: A novel option for US patients with acute pain-A review of its pharmacokinetics, abuse potential and clinical safety record. Harnett, M; Lu, L; Reines, SA, )	1.21
"Tramadol has been used for the treatment of premature ejaculation, however, the studies published for the same are not well designed. "	( Safety and efficacy of "on-demand" tramadol in patients with premature ejaculation: an updated meta-analysis. Bora, GS; Devana, SK; Mavuduru, RS; Sharma, AP; Sharma, G; Singh, SK; Tyagi, S, )	1.85
"tramadol dependence has negative effects on cognitive performance, which improves with extended abstinence."	( Effects of extended abstinence on cognitive functions in tramadol-dependent patients: A cohort study. Darwish, AM; Hassaan, SH; Khalifa, H, 2021)	2.31
"Tramadol has been reported to preserve or promote the immune response and may therefore be preferred to other opioids in cancer patients."	( New Insights on Tramadol and Immunomodulation. Hollmann, MW; La Caze, A; Parat, MO; Saeed, I; Shaw, PN, 2021)	1.69
"Tramadol has long been used as a well-tolerated alternative to other drugs in moderate pain because of its opioidergic and monoaminergic activities."	( Revisiting Tramadol: A Multi-Modal Agent for Pain Management. Barakat, A, 2019)	1.63
"Desmetramadol has the safety and efficacy of tramadol without its metabolic liabilities."	( Desmetramadol Has the Safety and Analgesic Profile of Tramadol Without Its Metabolic Liabilities: Consecutive Randomized, Double-Blind, Placebo- and Active Comparator-Controlled Trials. Johnson, MS; Kahn, SJ; Maeda, DY; Schuler, AD; Searle, SL; Webster, LR; Zebala, JA, 2019)	1.48
"Tramadol toxicity has not previously been reported in a cat."	( Tramadol toxicity in a cat: case report and literature review of serotonin syndrome. Indrawirawan, Y; McAlees, T, 2014)	3.29
"Tramadol has been shown to decrease ischemia-reperfusion injuries in myocardial or brain tissues. "	( Influence of tramadol on ischemia-reperfusion injury of rats' skeletal muscle. Asl, HA; Karimi, P; Mobarakeh, SZ; Takhtfooladi, HA; Takhtfooladi, MA, 2014)	2.21
"Tramadol has been used as an analgesic for several decades. "	( µ-Opioid receptor activation by tramadol and O-desmethyltramadol (M1). Minami, K; Miyano, K; Murphy, RS; Sudo, Y; Uezono, Y, 2015)	2.14
"Tramadol dependence has been studied recently after large-scale exposure. "	( Medical and Psychiatric Effects of Long-Term Dependence on High Dose of tramadol. El-Hadidy, MA; Helaly, AM, 2015)	2.09
"Tramadol abuse has not been well studied in Egypt."	( Adolescent tramadol use and abuse in Egypt. Abdel-Ghani, MM; Atwa, SA; Bassiony, MM; El-Gohari, H; Raya, Y; Salah El-Deen, GM; Yousef, U, 2015)	1.53
"Tramadol has a higher risk of fractures than some other opioid analgesics used to treat moderate-to-severe pain and, in the model described here, we investigate the cost effectiveness of transdermal buprenorphine treatment compared with tramadol in a high-risk population."	( Tramadol and the risk of fracture in an elderly female population: a cost utility assessment with comparison to transdermal buprenorphine. Akehurst, R; Dunlop, W; Hirst, A; Hirst, M; Knight, C, 2016)	2.6
"Tramadol has an important position as a Step II agent on the WHO pain ladder, where it is effective for a variety of syndromes in patients with mild to moderate pain intensity. "	( Tramadol in palliative care #290. Arnold, RM; Pruskowski, J, 2015)	3.3
"Tramadol has recently been isolated from the roots and bark of Nauclea latifolia. "	( Biomimetic synthesis of Tramadol. Boumendjel, A; Challal, S; De Waard, M; Ferreira Queiroz, E; Ferreira Queiroz, MM; Haudecoeur, R; Le Borgne, M; Lecerf-Schmidt, F; Lomberget, T; Marcourt, L; Peres, B; Robins, RJ; Sotoing Taiwe, G; Wolfender, JL, 2015)	2.17
"Tramadol addiction has recently been found to induce seizures in patients who exceed the recommended dose."	( Latarjet Procedure for Anterior Shoulder Instability Due to Tramadol-Induced Seizures: A Multicenter Study. Elassal, MA; Kamel, EM; Kandil, A; Khater, AH; Moustafa, R; Reda, W; Said, HG; Seifeldin, AF; Sobhy, MH, 2016)	1.4
"Tramadol addiction has evolved as an important cause of seizures that can result in shoulder dislocation. "	( Latarjet Procedure for Anterior Shoulder Instability Due to Tramadol-Induced Seizures: A Multicenter Study. Elassal, MA; Kamel, EM; Kandil, A; Khater, AH; Moustafa, R; Reda, W; Said, HG; Seifeldin, AF; Sobhy, MH, 2016)	2.12
"Tramadol has additional adverse effects unrelated to its opioid effects."	( "Weak" opioid analgesics. Codeine, dihydrocodeine and tramadol: no less risky than morphine. , 2016)	1.4
"Tramadol has gained traction as an analgesic of choice among pain practicing physicians. "	( What's Tramadol Got to Do with It? A Case Report of Rebound Hypoglycemia, a Reappraisal and Review of Potential Mechanisms. Chhatre, A; Odonkor, CA, )	2.03
"Tramadol has strong activity against Candida virulence factors such as yeast-to-hyphal form switching and adhesion."	( Tramadol, an Opioid Receptor Agonist: An Inhibitor of Growth, Morphogenesis, and Biofilm Formation in the Human Pathogen, Candida albicans. Karuppayil, SM; Kathwate, GH, 2016)	2.6
"Tramadol has abuse potential (even in therapeutic doses) more than Placebo but less than or comparable to Buprenorphine."	( Assessment of abuse liability of Tramadol among experienced drug users: Double-blind crossover randomized controlled trial. Das, M; Dhawan, A; Jain, R; Kaur, A, )	1.86
"Tramadol has been reported to cause seizures in therapeutic dosing and in overdose. "	( Pediatric tramadol ingestion resulting in seizurelike activity: a case series. Feldman, KW; Mazor, SS; Sotero, M; Sugar, NF, 2008)	2.19
"Tramadol overdose has been one of the most frequent causes of drug poisoning in the country in the recent years, especially in male young adults with history of substance abuse and mental disorders."	( Tramadol intoxication: a review of 114 cases. Abdollahi, M; Heydari, K; Sasanian, G; Shadnia, S; Soltaninejad, K, 2008)	2.51
"Tramadol has dual mechanisms of action by which analgesia may be achieved: micro-opioid receptor activation and enhancement of serotonin and norepinephrine transmission."	( Tramadol: basic pharmacology and emerging concepts. Burke, RS; Reeves, RR, 2008)	2.51
"Tramadol has a brief local anesthetic-like action when administered to ulnar nerve perineurally."	( Effects of perineural tramadol on sensory and motor conduction of ulnar nerve. Beyazova, M; Gökyar, I; Kaya, K; Oztürk, E; Sezer, OA; Zinnuroğlu, M, )	1.89
"Tramadol has become a major cause of drug-induced seizure recently. "	( Efficacy and safety of naloxone in the management of postseizure complaints of tramadol intoxicated patients: a self-controlled study. Abbasi, S; Ahmadi, SF; Ghadiri, M; Saidi, H, 2010)	2.03
"Tramadol has a better analgesic effect in third molar surgery than fentanyl and placebo."	( A comparison of the effects of midazolam/fentanyl and midazolam/tramadol for conscious intravenous sedation during third molar extraction. Garip, H; Göker, K; Göktay, O; Gönül, O; Satilmiş, T, 2011)	2.05
"Tramadol has been widely used as analgesic. "	( The tramadol metabolite O-desmethyl tramadol inhibits substance P-receptor functions expressed in Xenopus oocytes. Minami, K; Ogata, J; Uezono, Y; Yokoyama, T, 2011)	2.37
"Tramadol 2 mg/kg has local anesthetic and post-operative analgesic effect equal to lidocaine 1 mg/kg in minor surgeries performed subcutaneously. "	( Comparison of local anesthetic effects of tramadol and lidocaine used subcutaneously in minor surgeries with local anesthesia. Ahmadinejad, M; Akhlaghi, J; Birjandi, M; Heidari, M; Vahabi, S, 2011)	2.08
"Tramadol has been shown to have effects similar to those of local anesthetics."	( Postoperative analgesic effects of wound infiltration with tramadol and levobupivacaine in lumbar disk surgeries. Ayoglu, H; Erdogan, G; Hanci, V; Koksal, B; Okyay, RD; Ozyilmaz, K; Turan, IO; Yurtlu, S, 2012)	1.34
"Tramadol has low affinity for opioid receptors and has the ability to inhibit serotonin and noradrenaline reuptake."	( Cutaneous silent period in hand muscles is lengthened by tramadol: Evidence for monoaminergic modulation? Anastasio, MG; Brienza, M; Coppola, G; Parisi, L; Pierelli, F; Pujia, F; Serrao, M; Valente, GO; Vestrini, E, 2012)	1.35
"Tramadol has been marketed in the US since 1995. "	( Tramadol post-marketing surveillance in health care professionals. Campbell, ED; Dawson, KS; Knisely, JS; Schnoll, SH, 2002)	3.2
"Tramadol has been proven to exert a local anesthetic-type effect on peripheral nerves in both clinical and laboratory studies. "	( The effects of intrathecal tramadol on spinal somatosensory-evoked potentials and motor-evoked responses in rats. Chang, PJ; Chen, HH; Chu, KS; Jou, IM; Tsai, YC, 2003)	2.06
"Tramadol has similar analgesic properties, when compared with morphine. "	( Tramadol for pain relief in children undergoing tonsillectomy: a comparison with morphine. Engelhardt, T; Johnston, G; Steel, E; Veitch, DY, 2003)	3.2
"Tramadol has been administered peripherally to prolong analgesia after brachial plexus and neuraxial blocks. "	( Tramadol as adjunct to psoas compartment block with levobupivacaine 0.5%: a randomized double-blinded study. Mannion, S; Murphy, DB; O'Callaghan, S; Shorten, GD, 2005)	3.21
"Tramadol has a dual mechanism of action: weak mu opioid receptor agonist and a reuptake inhibitor of serotonin and noradrenaline."	( Tramadol: does it have a role in emergency medicine? Close, BR, 2005)	2.49
"Tramadol has not been compared with codeine, ibuprofen, or correctly dosed paracetamol (step-1 analgesic)."	( Tramadol oral solution: new drug. Poorly evaluated and potentially dangerous in children. , 2005)	2.49
"Tramadol has been approved in France since 1994 for the treatment of moderate to severe pain. "	( [Tramadol-induced hypoglycemia. 2 cases]. Authier, F; Dautriche, A; Duhoux, F; Grandvuillemin, A; Jolimoy, G; Sgro, C, 2006)	2.69
"Tramadol has been reported to be analgesic in clinical neuropathic pain, with varying levels of efficacy due to a patient population that has had neuropathic pain for a wide range of time."	( Altered antinociceptive efficacy of tramadol over time in rats with painful peripheral neuropathy. Hama, A; Sagen, J, 2007)	1.34
"Tramadol has been studied in cancer pain and neuropathic pain."	( Tramadol: does it have a role in cancer pain management? Prommer, EE, )	2.3
"Tramadol has dose- and time-dependent bactericidal activity against E. "	( The antibacterial activity of tramadol against bacteria associated with infectious complications after local or regional anesthesia. Bonnaure-Mallet, M; Donnio, PY; Jolivet-Gougeon, A; Repère, M; Shacoori, V; Tamanai-Shacoori, Z; Vo Van, JM, 2007)	2.07
"Tramadol ER has been shown to be safe and well-tolerated and may be a suitable alternative for patients with inadequate analgesic response or contraindications (eg, cardiovascular disease, gastrointestinal ulcer) to use of nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2 (COX-2) inhibitors."	( Extended-release Tramadol (ULTRAM ER): a pharmacotherapeutic, pharmacokinetic, and pharmacodynamic focus on effectiveness and safety in patients with chronic/persistent pain. Barkin, RL, )	1.19
"Tramadol has both opioid and monoaminergic agonist actions."	( A comparison of analgesic efficacy of tramadol and pethidine for management of postoperative pain in children: a randomized, controlled study. Ekemen, S; Ilhan, H; Tokar, B; Yelken, B, 2008)	1.34
"Tramadol has been the most-selling prescription analgesic in Germany for several years, and it is now available in many other European countries, but still there is a lack of adequately controlled clinical studies of its analgesic properties."	( Lack of analgesic effect of 50 and 100 mg oral tramadol after orthopaedic surgery: a randomized, double-blind, placebo and standard active drug comparison. Breivik, H; Grimstad, J; Stubhaug, A, 1995)	1.27
"Tramadol has also been used for the control of pain associated with labour and acute myocardial infarction, as well as for the management of trauma pain."	( Tramadol for the management of acute pain. Lehmann, KA, 1994)	2.45
"Tramadol has demonstrated efficacy in a few studies in the short term treatment of chronic pain of various origins."	( Tramadol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in acute and chronic pain states. Lee, CR; McTavish, D; Sorkin, EM, 1993)	2.45
"Tramadol has both opioid and monoaminergic agonist actions."	( Oral tramadol, a mu-opioid agonist and monoamine reuptake-blocker, and morphine for strong cancer-related pain. Osterwalder, B; Schimke, J; Senn, HJ; Wilder-Smith, CH, 1994)	1.52
"Tramadol has been determined in human plasma samples using a sensitive high-performance liquid chromatographic method. "	( High-performance liquid chromatographic determination of tramadol in human plasma. Anzenbacher, P; Kopecký, J; Nobilis, M; Pastera, J; Perlík, F; Svoboda, D, 1996)	1.98
"Tramadol has been used intraoperatively as part of balanced anaesthesia."	( A risk-benefit assessment of tramadol in the management of pain. Grond, S; Lehmann, KA; Radbruch, L, 1996)	1.31
"Tramadol has a minor delaying effect on colonic transit, but no effect on upper gastrointestinal transit or gut smooth muscle tone. "	( The analgesic tramadol has minimal effect on gastrointestinal motor function. Bettiga, A; Wilder-Smith, CH, 1997)	2.1
"Tramadol has been in clinical use in Germany since the late 1970s and has proven effective in both experimental and clinical pain without causing serious cardiovascular or respiratory side effects. "	( [Tramadol in acute pain]. Lehmann, KA, 1997)	2.65
"Tramadol has a favorable adverse-effect profile and therefore is likely to have an important role in the management of chronic pain syndromes."	( Nonsteroidal anti-inflammatory drugs, traditional opioids, and tramadol: contrasting therapies for the treatment of chronic pain. Aronson, MD, )	1.09
"Tramadol has been recommended for analgesia in parturients undergoing vaginal delivery. "	( Supplementation of general anaesthesia with tramadol or fentanyl in parturients undergoing elective caesarean section. Assaf, B; Baraka, A; Siddik, S, 1998)	2
"Tramadol has limited indication for management of acute pain in dentistry, possibly as an alternative analgesic when gastrointestinal side effects contraindicate the use of nonsteroidal anti-inflammatory drugs and when codeine/acetaminophen combination analgesics are not well-tolerated or are contraindicated."	( Pain management in dental practice: tramadol vs. codeine combinations. Moore, PA, 1999)	2.02
"Tramadol has shown variable effectiveness in the control of pain related to dental procedures."	( Analgesics in ophthalmic practice: a review of the oral non-narcotic agent tramadol. Barkin, RL; Gaynes, BI, 1999)	1.25
"Tramadol also has a low potential for abuse or dependence."	( Tramadol: a review of its use in perioperative pain. Perry, CM; Scott, LJ, 2000)	2.47
"Tramadol has a dual mechanism of action that includes weak agonistic effects at the mu-opioid receptor as well as inhibition of monoamine (serotonin, norepinephrine) re-uptake."	( Anticonvulsant and proconvulsant effects of tramadol, its enantiomers and its M1 metabolite in the rat kindling model of epilepsy. Friderichs, E; Löscher, W; Potschka, H, 2000)	1.29
"Tramadol has been investigated in various studies of OA pain and is indicated as an alternative to non-opioids, or as adjunctive therapy when non-opioid therapy is insufficient."	( Treatment of pain in osteoarthritis. Pavelka, K, 2000)	1.03
"Tramadol has weak opioid properties, and an analgesic effect that is mediated mainly by inhibition of the reuptake of norepinephrine and serotonin (5-hydroxytryptamine [5-HT]) and facilitation of 5-HT release (1,2) at the spinal cord. "	( The analgesic efficacy of tramadol is impaired by concurrent administration of ondansetron. De Witte, JL; Deloof, T; Schoenmaekers, B; Sessler, DI, 2001)	2.05
"1. Tramadol has been used clinically as an analgesic; however, the mechanism of its analgesic effects is still unknown. "	( Inhibitory effects of tramadol on nicotinic acetylcholine receptors in adrenal chromaffin cells and in Xenopus oocytes expressing alpha 7 receptors. Minami, K; Shibuya, I; Shigematsu, A; Shiraishi, M; Uezono, Y; Yanagihara, N, 2002)	1.25
"Tramadol has the advantage of being non-addictive, and not contraindicated for asthmatics, nor is it listed as dangerous and restricted in Thailand."	( A comparative study of tramadol and pethidine in laparoscopic interval sterilization. Chaturachinda, K; O-Prasertsawat, P; Padmasuta, K; Pausawasdi, S; Tangtrakul, S, 1988)	1.21

Excerpt	Reference	Relevance
"Tramadol is known to cause fewer adverse events (AEs) than other opioids. "	( Comparison of Online Patient Reviews and National Pharmacovigilance Data for Tramadol-Related Adverse Events: Comparative Observational Study. Choi, SH; Kwon, JW; Park, S; Song, YK, 2022)	2.39
"Tramadol may lower the seizure threshold; however, there is no conclusive evidence to confirm this. "	( Association between tramadol use and seizures: A nationwide case-case-time-control study. Jeon, HL; Kim, JH; Lee, H; Park, S; Shin, JY, 2022)	2.49
"Tramadol did not cause significant postoperative nausea and vomiting."	( The analgesic Efficacy and Safety of Topically Applied Tramadol in Peritonsillar Space During Pediatric Adenotonsillectomy: A Meta-Analysis. Cho, JH; Hwang, SH; Kang, YJ, 2023)	1.88
"Tramadol did not cause testicular oxidative stress but impaired testicular function by suppressing testosterone, FSH and LH secretion."	( Vitamin E administration does not ameliorate tramadol-associated impairment of testicular function in Wistar rats. Beshel, FN; Mkpe, ID; Nwangwa, JN; Ofuru, OS; Sam-Ekpe, VG; Stephen, GI; Udefa, AL, 2020)	1.54
"The tramadol group show a lower pain levels at the first, third and seventh postoperatively days when comparing to the control group."	( Influence of tramadol on functional recovery of acute spinal cord injury in rats. Chaves, RHF; Furlaneto, IP; Lima, AR; Oliveira, CP; Penha, NEAD; Rodrigues, EM; Santos, DASD; Silva, RC; Souza, CC; Teixeira, RKC, 2018)	1.33
"Tramadol may cause rebound hypoglycemia in patients via interference of the intrinsic euglycemia-restoration pathways and a blunted autonomic counter-regulatory response to antecedent hypoglycemia."	( What's Tramadol Got to Do with It? A Case Report of Rebound Hypoglycemia, a Reappraisal and Review of Potential Mechanisms. Chhatre, A; Odonkor, CA, )	1.31
"Tramadol can cause life-threatening toxicity in overdose; however, data on its toxicity in children are lacking. "	( Characterizing the Toxicity and Dose-Effect Profile of Tramadol Ingestions in Children. Gonzales, L; Klein-Schwartz, W; Stassinos, GL, 2019)	2.2
"Tramadol seems to cause a shorter duration of labour and lower incidence of maternal side-effects."	( A comparison of tramadol and pethidine analgesia on the duration of labour: a randomised clinical trial. Khooshideh, M; Shahriari, A, 2009)	1.42
"Mean tramadol dose was lower among females than males (males, 2413 mg vs."	( Dose-independent occurrence of seizure with tramadol. Abdollahi, M; Asadi, Z; Fayaznouri, M; Panahandeh, R; Talaie, H, 2009)	1.07
"Tramadol can suppress opioid withdrawal, and chronic administration can produce opioid physical dependence; however, diversion and abuse of tramadol is low."	( Discriminative stimulus effects of tramadol in humans. Bigelow, GE; Duke, AN; Lanier, RK; Strain, EC, 2011)	1.37
"tramadol plays an important role in efficacy and safety for controlling ocular pain and inflammation after LASEK."	( [Clinical observation of tramadol on postoperative painment from LASEK]. Li, Z; Wang, P; Zhao, R, 2005)	2.07
"Tramadol did not produce significant increases on measures of positive drug effects nor any clinically significant physiologic changes."	( Modest opioid withdrawal suppression efficacy of oral tramadol in humans. Bigelow, GE; Lofwall, MR; Strain, EC; Walsh, SL, 2007)	1.31
"Tramadol appeared to cause more nausea and vomiting than morphine."	( Comparison of tramadol and morphine via subcutaneous PCA following major orthopaedic surgery. Boon, J; De Wet, C; Hopkins, D; Murphy, J; Potgieter, D; Shipton, EA; Van derMerwe, CA, 1998)	1.38
"Tramadol may cause awareness and EEG activation during anaesthesia. "	( Tramadol or morphine administered during operation: a study of immediate postoperative effects after abdominal hysterectomy. Coetzee, JF; van Loggerenberg, H, 1998)	3.19
"Tramadol in lower doses (0.5-1 mg kg(-1)) was an efficient preemptive analgesic that could be used at induction of anesthesia in adenotonsillectomies of children for providing both good analgesia during operation as supplementation to propofol anesthesia and postoperative analgesia in only early period."	( Relief of posttonsillectomy pain with low-dose tramadol given at induction of anesthesia in children. Akçabay, M; Kemaloğlu, YK; Ozköse, Z; Sezenler, S, 2000)	2.01

Excerpt	Reference	Relevance
"Tramadol treated pregnant rats showed significantly (p < .05) reduced red blood cells, hematocrit, hemoglobin, and platelets with reference to control group."	( Maternotoxicity and fetotoxicity in Rattus norvegicus albinus exposed to tramadol during the late phase of pregnancy. Abdel-Daim, MM; Akhtar, MF; Baig, MMFA; Rasul, A; Saleem, A; Saleem, M; Sharif, A; Younas, S, 2021)	1.57
"tramadol in the treatment of moderate pain from extremity injuries."	( Subcutaneous versus intravenous tramadol for extremity injury with moderate pain in the emergency department: a randomised controlled noninferiority trial. Abdullah, AA; Ang, BT; Bustam, A; Mohd Nazri, MZA; Noor Azhar, AM; Nor Azman, AIH; Poh, K; Subramaniam, T; Zambri, A, 2023)	1.92
"Tramadol treatment caused the reduction of incapacitation and edema. "	( Intrathecally injected tramadol reduces articular incapacitation and edema in a rat model of lipopolysaccharide (LPS)-induced reactive arthritis. Benedet, PO; Callado de Oliveira, DMM; Lucena, F; Melleu, FF; Mujica, EMM; Norões, MM; Ribeiro, LFC; Stein, T; Tonussi, CR, 2019)	2.27
"Tramadol treatment did not affect the MGS or burrowing performance."	( A safe bet? Inter-laboratory variability in behaviour-based severity assessment. Abdelrahman, A; Bleich, A; Durst, M; Häger, C; Jirkof, P; Keubler, L; Potschka, H; Struve, B; Talbot, SR; Vollmar, B; Zechner, D, 2020)	1.28
"Tramadol treated groups showed degenerative changes in dentate gyrus (DG) granule cells, pyramidal neurons of CA1and CA3 fields in the form of electron-dense or rarified cytoplasm, dilated rER and mitochondrial changes."	( Tramadol administration induced hippocampal cells apoptosis, astrogliosis, and microgliosis in juvenile and adult male mice, histological and immunohistochemical study. Abdel Mola, AF; Hussein, OA; Rateb, A, 2020)	2.72
"Tramadol treatment for 72 h did not alter Cx43 expression, but decreased Cx43 phosphorylation accompanied with reduced p-ERK and p-JNK."	( Tramadol attenuates the sensitivity of glioblastoma to temozolomide through the suppression of Cx43‑mediated gap junction intercellular communication. Huang, H; Ma, L; Peng, J; Peng, Y; Shao, M; Wang, L; Xia, Z; Zhong, G; Zhu, Z, 2018)	2.64
"In tramadol-treated animals, the dark neurons (DNs) and apoptotic cells in CA1, CA3 and DG increased (P < 0.05), while concurrent intake of crocin decreased the number of DNs and apoptotic cells in these areas (P < 0.05)."	( The effects of tramadol administration on hippocampal cell apoptosis, learning and memory in adult rats and neuroprotective effects of crocin. Baghishani, F; Ebrahimzadeh-Bideskan, A; Hosseini, M; Hosseinzadeh, H; Mohammadipour, A, 2018)	1.35
"In tramadol-treated patients, CYP2D6DUP allele carriers followed by those carrying CYP2D61, displayed higher levels of urinary tramadol major active metabolite, O-desmethyltramadol (M1) and serum lipid peroxidation along with lower levels of total antioxidants than those carrying other impaired function alleles (CYP2D64&10), suggesting oxidative stress."	( Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6) are associated with long term tramadol treatment-induced oxidative damage and hepatotoxicity. Arafa, MH; Atteia, HH, 2018)	1.22
"The tramadol-treated surrogate dams showed a statistically significant increase in the number of offspring that survived to weaning."	( Effects of using the analgesic tramadol in mice undergoing embryo transfer surgery. Alexakos, P; Balafas, E; Kakazanis, Z; Kostomitsopoulos, N; Koutroli, E; Symeon, I; Voyiatzaki, C, 2014)	1.17
"Tramadol treatment could be optimized in these at-risk individuals, consequently improving patient outcome and safety."	( Near-fatal tramadol cardiotoxicity in a CYP2D6 ultrarapid metabolizer. Allorge, D; Broly, F; Elkalioubie, A; Fourrier, F; Garat, A; Robriquet, L; Wiart, JF, 2011)	1.48
"Tramadol/acetaminophen-treated subjects also had significantly less pain at the end of the study (53 +/- 32 vs."	( Tramadol and acetaminophen combination tablets in the treatment of fibromyalgia pain: a double-blind, randomized, placebo-controlled study. Bennett, RM; Kamin, M; Karim, R; Rosenthal, N, 2003)	2.48
"Tramadol ER-treated subjects were nearly twice as likely as placebo subjects to have clinically meaningful pain reduction at 12 weeks, defined as 30 mm or greater reduction (odds ratio [OR] = 1.84, P < 0.001) or 30% or greater reduction (OR = 1.95, P < 0.001) in pain."	( Pain relief and pain-related sleep disturbance with extended-release tramadol in patients with osteoarthritis. Freedman, J; Gajria, K; Janagap, C; Kosinski, M; Schein, J, 2007)	1.3
"CR tramadol treatment was preferred by 55.8% of patients (P=0.0005) versus 20.8% and 23.4% of patients who chose placebo or had no preference, respectively."	( A randomized, double-blind, crossover comparison of the efficacy and safety of oral controlled-release tramadol and placebo in patients with painful osteoarthritis. Akhras, R; Bartlett, JM; Beaulieu, AD; Callaghan, DJ; Darke, AC; Eisenhoffer, J; Harsanyi, Z; Knight, R; Kraag, GR; O'Mahony, WF; Piraino, PS; Thorne, C, )	0.86
"Treatment with tramadol was associated with an increased risk of bleeding peptic ulcer. "	( Is tramadol associated to bleeding peptic ulcer? A nationwide case-control study in hospitalized Swedish patients. Andersson, ML; Bilén, K; Broström, O; Järnbert-Pettersson, H; Lindh, JD; Mannheimer, B, 2019)	1.49
"Treatment with tramadol, given (30 min earlier) by oral route (p.o.) at the doses of 10, 20 and 40 mg/kg, decreased immobility time in the FST."	( Involvement of L-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effect of tramadol in the rat forced swimming test. Bortolatto, CF; Jesse, CR; Nogueira, CW; Rocha, JB; Savegnago, L, 2008)	0.9
"Pretreatment with tramadol showed a dose-depended inhibitory effect on c-fos expression and serum IL-6 production,but not in Group T1."	( [Tramadol inhibits c-fos expression in spinal cord dorsal horn and serum IL-6 levels induced by plantar incision in rats]. CHEN, QL; LIU, YM; WANG, KR; ZHENG, YY; ZHU, SM, 2009)	1.59
"Pretreatment with tramadol can produce dose-dependent inhibitory effect on c-fos expression in spinal cord dorsal horn and then suppress the inflammatory response to the trauma."	( [Tramadol inhibits c-fos expression in spinal cord dorsal horn and serum IL-6 levels induced by plantar incision in rats]. CHEN, QL; LIU, YM; WANG, KR; ZHENG, YY; ZHU, SM, 2009)	1.6
"Pretreatment with tramadol by the i.p."	( Evidence for the involvement of glutamatergic and neurokinin 1 receptors in the antinociception elicited by tramadol in mice. Jesse, CR; Nogueira, CW, 2010)	0.9
"Treatment with tramadol or opioids is usually reserved for severe pain associated with OA."	( Treatment options for osteoarthritis: considerations for older adults. Dunican, KC; Lynch, AM; Seed, SM, 2011)	0.71
"Pretreatment with tramadol enhances the ketamine-induced antidepressant effects, which is associated with the increased expression of mTOR in rat hippocampus and prefrontal cortex."	( Tramadol pretreatment enhances ketamine-induced antidepressant effects and increases mammalian target of rapamycin in rat hippocampus and prefrontal cortex. Gao, ZQ; Li, WY; Liu, XL; Yang, C; Yang, JJ; Yu, HY; Zhou, ZQ, 2012)	2.15
"Treatment with tramadol 50 to 200 mg per day was associated with significant pain reduction in terms of enhanced pain relief, reduced sleep interference, greater global improvement, diminished side-effect profile, and improved QOL in PHN patients from North India. "	( A randomized, prospective study of efficacy and safety of oral tramadol in the management of post-herpetic neuralgia in patients from north India. Ahmed, RS; Banerjee, BD; Bhattacharya, SN; Dhakate, G; Jain, S; Mediratta, PK; Nasare, N; Saxena, AK, 2013)	0.98
"Pretreatment with tramadol 60 sec before propofol injection and propofol-lidocaine mixture were significantly reduced propofol injection pain when compared to placebo in children."	( Prevention of propofol injection pain in children: a comparison of pretreatment with tramadol and propofol-lidocaine mixture. Borazan, H; Et, T; Kececioglu, A; Otelcioglu, S; Sahin, O; Uluer, MS, 2012)	0.94
"Pretreatment with tramadol reduced the percentage of patients with at least moderate pain from 40% to 20% (P=0.029)."	( Pain during bone marrow aspiration: prevalence and prevention. Delforge, M; Evers, G; Nijs, K; Vanderschueren, S; Vanhelleputte, P, 2003)	0.64
"Treatment with tramadol ER results in statistically significant and clinically important and sustained improvements in pain, stiffness, physical function, global status, and sleep in patients with chronic pain."	( Efficacy and safety of extended-release, once-daily tramadol in chronic pain: a randomized 12-week clinical trial in osteoarthritis of the knee. Albert, K; Babul, N; Chipman, H; Gana, T; Noveck, R; Roth, SH, 2004)	0.91

Excerpt	Reference	Relevance
" Both drugs produced acceptable analgesia, and there were no clinically significant adverse events."	( Efficacy and safety of tramadol versus morphine for moderate and severe postoperative pain with special regard to respiratory depression. Erdmann, W; Houmes, RJ; Lachmann, B; Verkaaik, A; Voets, MA, 1992)	0.59
" Assessment of laboratory screening, adverse events, vital signs and blood gas monitoring showed no serious drug-related events."	( Analgesic efficacy and safety of tramadol enantiomers in comparison with the racemate: a randomised, double-blind study with gynaecological patients using intravenous patient-controlled analgesia. Grond, S; Hennig, U; Lehmann, KA; Meuser, T; Zech, D, 1995)	0.57
" Adverse effects and safety concerns associated with many analgesics have limited the use of these agents and contributed to the undertreatment of pain."	( Pharmacokinetics, efficacy, and safety of analgesia with a focus on tramadol HCl. Gibson, TP, 1996)	0.53
" Further analyses were performed to provide information about the gender-, age- and dose-related distribution of adverse reactions The prevalence of side effects was calculated by comparing the number of symptoms with the number of patients."	( [Tolerance and safety of tramadol use. Results of international studies and data from drug surveillance]. Cossmann, M; Kohnen, C; Langford, R; McCartney, C, 1997)	0.6
"Cardiopulmonary adverse effects are commonly observed in patients undergoing colonoscopy with sedation."	( Complications and adverse effects of colonoscopy with selective sedation. Bernhard, G; Eckardt, AJ; Eckardt, VF; Kanzler, G; Schmitt, T, 1999)	0.3
" Additional adverse effects occurring during or after the procedure were noted in the patients' protocol."	( Complications and adverse effects of colonoscopy with selective sedation. Bernhard, G; Eckardt, AJ; Eckardt, VF; Kanzler, G; Schmitt, T, 1999)	0.3
" Adverse effects occurred in 59 patients (2."	( Complications and adverse effects of colonoscopy with selective sedation. Bernhard, G; Eckardt, AJ; Eckardt, VF; Kanzler, G; Schmitt, T, 1999)	0.3
" If selective sedation is used, cardiopulmonary adverse effects occur in approximately 2% of all patients, most of whom require no medical intervention."	( Complications and adverse effects of colonoscopy with selective sedation. Bernhard, G; Eckardt, AJ; Eckardt, VF; Kanzler, G; Schmitt, T, 1999)	0.3
"Tramadol, a weak opioid mu-receptor agonist, may have a favourable potency and side effect profile for intravenous patient-controlled analgesia (PCA)."	( Efficacy and side effects of tramadol versus oxycodone for patient-controlled analgesia after maxillofacial surgery. Rosenberg, PH; Silvasti, M; Svartling, N; Tarkkila, P; Tuominen, M, 1999)	2.04
" A significantly higher percentage of adverse gastrointestinal effects was found in patients given tramadol (42."	( Efficacy and safety of dipyrone versus tramadol in the management of pain after hysterectomy: a randomized, double-blind, multicenter study. Cabrera, J; Calderón, E; Cámara, J; de la Torre, MR; García-Magaz, I; Gómez, JL; Herrera, J; Martínez, T; Montero, A; Ortiz, P; Porres, R; Rodríguez, MJ; Ruiz, J; Torres, LM, )	0.62
" The most common treatment-related adverse events for tramadol/APAP were somnolence (6."	( Efficacy and safety of tramadol/acetaminophen tablets (Ultracet) as add-on therapy for osteoarthritis pain in subjects receiving a COX-2 nonsteroidal antiinflammatory drug: a multicenter, randomized, double-blind, placebo-controlled trial. Emkey, R; Jordan, D; Kamin, M; Rosenthal, N; Wu, SC, 2004)	0.88
"5 mg/APAP 325 mg combination tablets were effective and safe as add-on therapy with COX-2 NSAID for treatment of OA pain."	( Efficacy and safety of tramadol/acetaminophen tablets (Ultracet) as add-on therapy for osteoarthritis pain in subjects receiving a COX-2 nonsteroidal antiinflammatory drug: a multicenter, randomized, double-blind, placebo-controlled trial. Emkey, R; Jordan, D; Kamin, M; Rosenthal, N; Wu, SC, 2004)	0.63
" Outcome measures included Arthritis Pain Intensity Visual Analogue Scale (VAS), Western Ontario and McMaster Universities Arthritis Scale (WOMAC) Pain, Stiffness, Physical Function VAS subscales, Patient and Physician Global Assessment of Therapy, Sleep, dropouts due to insufficient therapeutic effect, and adverse events."	( Efficacy and safety of extended-release, once-daily tramadol in chronic pain: a randomized 12-week clinical trial in osteoarthritis of the knee. Albert, K; Babul, N; Chipman, H; Gana, T; Noveck, R; Roth, SH, 2004)	0.57
" The most common treatment related adverse events with tramadol/APAP were nausea (12."	( Analgesic efficacy and safety of tramadol/ acetaminophen combination tablets (Ultracet) in treatment of chronic low back pain: a multicenter, outpatient, randomized, double blind, placebo controlled trial. Beaulieu, A; Fortin, L; Kamin, M; Peloso, PM; Rosenthal, N, 2004)	0.85
" --It is argued, in this paper, that codeine phosphate is an unpredictable pro-drug that does not equate to a safe and effective method of providing analgesia post-craniotomy."	( A review of the efficacy and safety of opioid analgesics post-craniotomy. Roberts, G, )	0.13
" In the period 1 January 1992--30 November 2003, the Netherlands Pharmacovigilance Centre Lareb received 299 reports concerning 522 adverse drug reactions associated with the use of tramadol."	( [Side effects of tramadol: 12 years of experience in the Netherlands]. Kabel, JS; van Puijenbroek, EP, 2005)	0.86
" Although opioids are reported to be effective in pain management, their toxic effects should be kept in mind during chronic usage."	( Liver and kidney toxicity in chronic use of opioids: an experimental long term treatment model. Atici, S; Cinel, I; Cinel, L; Doruk, N; Eskandari, G; Oral, U, 2005)	0.33
" Main outcome measures were number of voids per 24 h, urine volume per void and episodes of urge incontinence per 24 h on a frequency volume chart and detailed recording of adverse effect."	( Safety and efficacy of tramadol in the treatment of idiopathic detrusor overactivity: a double-blind, placebo-controlled, randomized study. Hosseini, SY; Safarinejad, MR, 2006)	0.64
"With the objective of comparing incidence of adverse events of the opioids codeine, hydrocodone, and tramadol in the relief of cancer pain, we conducted a randomized controlled trial in which patients with cancer were randomly assigned according to a computer-generated schedule to receive one of the three opioids."	( Incidence of weak opioids adverse events in the management of cancer pain: a double-blind comparative trial. Bravo, LE; Castillo, JM; Castillo, MP; Castro, F; Daza, P; Montoya, O; Restrepo, JM; Rodriguez, MF; Rodriguez, RF, 2007)	0.56
" Common adverse events, regardless of treatment relationship, were nausea, dizziness (excluding vertigo), and constipation."	( Open-label study of the safety and effectiveness of long-term therapy with extended-release tramadol in the management of chronic nonmalignant pain. Fleming, RR; Gana, TJ; Pascual, ML; Vorsanger, GJ, 2007)	0.56
" The type and incidence of adverse events were typical of tramadol (nausea, dizziness/vertigo, vomiting, somnolence, and constipation) and the intensity was mild to moderate in 87percent of patients who experienced them regardless of dose."	( Efficacy and safety of 12 weeks of osteoarthritic pain therapy with once-daily tramadol (Tramadol Contramid OAD). Aparicio, RT; Bouchard, S; Ellerbusch, MT; Fishman, RL; Fortier, L; Jain, AK; Kistler, CJ; Robertson, S; Shirley, ME; Swami, SS, )	0.6
" Tramadol ER has been shown to be safe and well-tolerated and may be a suitable alternative for patients with inadequate analgesic response or contraindications (eg, cardiovascular disease, gastrointestinal ulcer) to use of nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2 (COX-2) inhibitors."	( Extended-release Tramadol (ULTRAM ER): a pharmacotherapeutic, pharmacokinetic, and pharmacodynamic focus on effectiveness and safety in patients with chronic/persistent pain. Barkin, RL, )	1.38
" Safety was evaluated by retrieving information about the nature and incidence of adverse events (AE), whether they were related to the study compound, and the percentage considered being serious."	( High dose transdermal buprenorphine for moderate to severe pain in spanish pain centres--a retrospective multicenter safety and efficacy study. Barutell, C; Camba, A; González-Escalada, JR; Rodríguez, M, )	0.13
"Transdermal buprenorphine was an effective and considerably safe drug for relieving chronic moderate to severe pain."	( High dose transdermal buprenorphine for moderate to severe pain in spanish pain centres--a retrospective multicenter safety and efficacy study. Barutell, C; Camba, A; González-Escalada, JR; Rodríguez, M, )	0.13
" The incidence of adverse events (AEs) was comparable in the 2 treatment groups: 226 AEs were reported in 61 patients (88."	( Efficacy and safety of low-dose transdermal buprenorphine patches (5, 10, and 20 microg/h) versus prolonged-release tramadol tablets (75, 100, 150, and 200 mg) in patients with chronic osteoarthritis pain: a 12-week, randomized, open-label, controlled, pa Berggren, AC; Karlsson, M, 2009)	0.56
"Short-term exposure of transformed cells to cisplatin reduced the clonogenic survival in low-density cultures (without gap junction formation) and in high density (with gap junction formation), but the toxic effect was greater at high density."	( Tramadol and flurbiprofen depress the cytotoxicity of cisplatin via their effects on gap junctions. Harris, AL; He, B; Hong, X; Liu, B; Tao, L; Tong, X; Wang, L; Wang, Q; Ye, H, 2009)	1.8
"This study assessed the efficacy and adverse effects of preoperatively administered lornoxicam versus tramadol in adults, for post-tonsillectomy pain."	( Effects of preoperative lornoxicam versus tramadol on postoperative pain and adverse effects in adult tonsillectomy patients. Akçabay, M; Arslan, M; Işik, B; Ozsoylar, O, 2009)	0.83
" Adverse effects in the postoperative 6h period were noted."	( Effects of preoperative lornoxicam versus tramadol on postoperative pain and adverse effects in adult tonsillectomy patients. Akçabay, M; Arslan, M; Işik, B; Ozsoylar, O, 2009)	0.62
"To review the safety profile of tramadol hydrochloride (tramadol) in the treatment of chronic osteoarthritis pain, with specific reference to the incidence of adverse events (AEs) reported in large clinical trials."	( Adverse event profile of tramadol in recent clinical studies of chronic osteoarthritis pain. Benson, CJ; Boswell, KA; Langley, PC; Patkar, AD; Schein, JR, 2010)	0.95
"The frequency of adverse effects (including therapeutic failure) with the medications tramadol and dipirona were described and estimated."	( [Adverse events associated with tramadol and dipirona administration in a level III hospital]. Montoya, GA; Parra, MF; Vaca, C, 2009)	0.86
", Colombia, adverse events associated with dipirone and tramadol were rigorously tracked in patients hospitalized in the internal medicine, as well as the orthopedics and surgery departments."	( [Adverse events associated with tramadol and dipirona administration in a level III hospital]. Montoya, GA; Parra, MF; Vaca, C, 2009)	0.88
"6% (16 cases) were classes as serious adverse events."	( [Adverse events associated with tramadol and dipirona administration in a level III hospital]. Montoya, GA; Parra, MF; Vaca, C, 2009)	0.64
"An unacceptable level of preventable adverse events was described that impacted the well-being of patients, as well as the costs associated with remedial treatment."	( [Adverse events associated with tramadol and dipirona administration in a level III hospital]. Montoya, GA; Parra, MF; Vaca, C, 2009)	0.64
" The efficacy measures included VAS scores and adverse effect assessment 10, 30, and 60 minutes after the administration of tramadol/acetaminophen."	( Efficacy and safety of tramadol/acetaminophen in the treatment of breakthrough pain in cancer patients. Chang, CS; Chung, CY; Ho, ML; Hsu, NC; Lin, HY; Wang, CC, 2010)	0.88
"Tramadol/acetaminophen might be efficacious and safe in the treatment of breakthrough pain in cancer."	( Efficacy and safety of tramadol/acetaminophen in the treatment of breakthrough pain in cancer patients. Chang, CS; Chung, CY; Ho, ML; Hsu, NC; Lin, HY; Wang, CC, 2010)	2.11
"5%) reported at least one adverse event (AE)."	( Epidemiological data, efficacy and safety of a paracetamol-tramadol fixed combination in the treatment of moderate-to-severe pain. SALZA: a post-marketing study in general practice. Ganry, H; Mejjad, O; Serrie, A, 2011)	0.61
" For patients with previous long-term tramadol or tilidate/naloxone treatment the switch to the 7-day buprenorphine matrix patch proved to be effective and safe for the management of chronic pain."	( [The transdermal 7-day buprenorphine patch--an effective and safe treatment option, if tramadol or tilidate/naloxone is insufficient. Results of a non-interventional study]. Heckes, B; Ritzdorf, I; Schutter, U, 2010)	0.85
" Tramadol is generally considered to be devoid of any serious adverse effects of traditional opioid receptor agonists, such as respiratory depression and drug dependence."	( Near-fatal tramadol cardiotoxicity in a CYP2D6 ultrarapid metabolizer. Allorge, D; Broly, F; Elkalioubie, A; Fourrier, F; Garat, A; Robriquet, L; Wiart, JF, 2011)	1.67
" Intravaginal ejaculatory latency time (IELT), intercourse satisfaction of the partners, total therapeutic effectiveness, adverse reactions, and hepatic and renal function of the patients were recorded and compared before and after the treatment."	( [Safety and efficacy of tramadol hydrochloride with behavioral modification in the treatment of premature ejaculation]. Chen, SH; Wu, FH; Xiong, GG; Yao, WL, 2011)	0.68
" Adverse reactions occurred in 10 cases (27."	( [Safety and efficacy of tramadol hydrochloride with behavioral modification in the treatment of premature ejaculation]. Chen, SH; Wu, FH; Xiong, GG; Yao, WL, 2011)	0.68
" Among studies that provided comprehensive adverse event data, safety and tolerability observations in men with PE were generally similar to those observed in other populations; however, with the exception of dapoxetine, known SSRI-class effects (e."	( Oral agents for the treatment of premature ejaculation: review of efficacy and safety in the context of the recent International Society for Sexual Medicine criteria for lifelong premature ejaculation. McMahon, CG; Porst, H, 2011)	0.37
"This systematic review of well-controlled clinical trials in PE has demonstrated that while many oral agents, particularly SSRIs, tramadol, and dapoxetine, have proven effective and safe for the treatment of men with PE, few have been evaluated for their effects on the specific elements of the ISSM criteria."	( Oral agents for the treatment of premature ejaculation: review of efficacy and safety in the context of the recent International Society for Sexual Medicine criteria for lifelong premature ejaculation. McMahon, CG; Porst, H, 2011)	0.57
"On-demand 62mg tramadol ODT is an effective treatment for PE in a low and safe therapeutic dose and provides a new option for managing mild to severe PE."	( A randomized double-blind, placebo-controlled multicenter study to evaluate the efficacy and safety of two doses of the tramadol orally disintegrating tablet for the treatment of premature ejaculation within less than 2 minutes. Bar-Or, D; Orlando, A; Salottolo, KM; Winkler, JV, 2012)	0.94
"To provide family physicians with a practical clinical summary of the Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain, developed by the National Opioid Use Guideline Group."	( Canadian guideline for safe and effective use of opioids for chronic noncancer pain: clinical summary for family physicians. Part 1: general population. Kahan, M; Mailis-Gagnon, A; Srivastava, A; Wilson, L, 2011)	0.37
" End points included intravaginal ejaculation latency time (in minutes), adverse events, and patient-reported outcome assessments."	( Efficacy and safety of tramadol for premature ejaculation: a systematic review and meta-analysis. Cheng, Y; Duan, X; Luo, D; Tian, Y; Wang, K; Wu, T; Yue, X, 2012)	0.69
"Treatment with tramadol 50 to 200 mg per day was associated with significant pain reduction in terms of enhanced pain relief, reduced sleep interference, greater global improvement, diminished side-effect profile, and improved QOL in PHN patients from North India."	( A randomized, prospective study of efficacy and safety of oral tramadol in the management of post-herpetic neuralgia in patients from north India. Ahmed, RS; Banerjee, BD; Bhattacharya, SN; Dhakate, G; Jain, S; Mediratta, PK; Nasare, N; Saxena, AK, 2013)	0.98
" The purpose of this study was to evaluate the efficacy, safety, and adverse events of extended release tramadol in Taiwanese patients with moderate to severe chronic noncancer pain."	( An open label trial of the effects and safety profile of extended-release tramadol in the management of chronic pain. Hsieh, YJ; Hsu, SK; Lin, CJ; Yeh, CC, 2012)	0.82
" In this study, the reported adverse events were similar to those of previous studies."	( An open label trial of the effects and safety profile of extended-release tramadol in the management of chronic pain. Hsieh, YJ; Hsu, SK; Lin, CJ; Yeh, CC, 2012)	0.61
"Patients with chronic pain could obtain significantly better pain relief after the switch to larger doses of extended-release tramadol with safety and without severe adverse effects in a short period of time."	( An open label trial of the effects and safety profile of extended-release tramadol in the management of chronic pain. Hsieh, YJ; Hsu, SK; Lin, CJ; Yeh, CC, 2012)	0.82
" Patients were informed to report any adverse effect encountered during the study period."	( Efficacy and safety of flupirtine maleate and tramadol hydrochloride in postoperative pain management--a prospective randomised double blinded study. Biswas, A; Das, AK; Kamal, F; Naser, SM; Prakash, R; Rahaman, QM; Sarkar, N, 2012)	0.64
" We concluded that using tramadol hydrochloride at different doses on demand for the treatment of PE is effective, safe and tolerable, with minimal undesirable effects, and approval for this indication should be sought."	( Safety and efficacy of tramadol hydrochloride on treatment of premature ejaculation. Eassa, BI; El-Shazly, MA, 2013)	1
" A total of 12 subjects in the gabapentin group and 15 subjects in the amitriptyline group experienced adverse events which were of mild to moderate grades."	( A comparative study of efficacy and safety of gabapentin versus amitriptyline as coanalgesics in patients receiving opioid analgesics for neuropathic pain in malignancy. Banerjee, M; Basu, J; Bhattacharya, B; Ghosh, B; Mondal, S; Pal, S, )	0.13
" Secondary end points included quality of life (Korean Short Form-36), functionality (Korean Oswestry Disability Index), and adverse events."	( A randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of the extended-release tramadol hydrochloride/acetaminophen fixed-dose combination tablet for the treatment of chronic low back pain. Lee, CS; Lee, JH, 2013)	0.59
" Adverse events were reported more frequently with TA-ER than with placebo; the most common adverse events reported were nausea, dizziness, constipation, and vomiting."	( A randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of the extended-release tramadol hydrochloride/acetaminophen fixed-dose combination tablet for the treatment of chronic low back pain. Lee, CS; Lee, JH, 2013)	0.59
" The results showed that tramadol had less analgesic efficacy and an increased risk of adverse effects compared with NSAID."	( Analgesic efficacy and safety of single-dose tramadol and non-steroidal anti-inflammatory drugs in operations on the third molars: a systematic review and meta-analysis. Aragon-Martinez, OH; de Jesús Pozos-Guillén, A; Isiordia-Espinoza, MA, 2014)	0.97
" Overall adverse events in the 2 treatment groups were also compared."	( Efficacy and safety of transdermal fentanyl in the control of postoperative pain after photorefractive keratectomy. Bae, JH; Choi, CY; Kim, JM; Kim, YJ; Lee, YW, 2014)	0.4
" Total number of patients who reported adverse events was significantly higher in the fentanyl group (P=0."	( Efficacy and safety of transdermal fentanyl in the control of postoperative pain after photorefractive keratectomy. Bae, JH; Choi, CY; Kim, JM; Kim, YJ; Lee, YW, 2014)	0.4
"TDF was more effective in the control of postoperative pain after PRK than tramadol/acetaminophen and no irreversible or severe adverse effect was reported with 12 μg/h concentration."	( Efficacy and safety of transdermal fentanyl in the control of postoperative pain after photorefractive keratectomy. Bae, JH; Choi, CY; Kim, JM; Kim, YJ; Lee, YW, 2014)	0.63
" Secondary endpoints included SPID at additional time points, total pain relief at all on-therapy time points (TOTPAR), sum of SPID and TOTPAR at all on-therapy time points (SPID + TOTPAR), use of rescue medication, subjective pain assessment (PGIC, Patient Global Impression of Change), and adverse events (AEs)."	( A randomized study to compare the efficacy and safety of extended-release and immediate-release tramadol HCl/acetaminophen in patients with acute pain following total knee replacement. Bin, SI; Chang, N; Cho, SD; Choi, CH; Ha, CW; Kang, SB; Kyung, HS; Lee, JH; Lee, MC; Park, YB; Rhim, HY; Seo, SS, 2015)	0.64
"This study demonstrated that the analgesic effect of TA-ER is non-inferior to TA-IR, and supports TA-ER as an effective and safe treatment for moderate to severe acute pain post total knee replacement."	( A randomized study to compare the efficacy and safety of extended-release and immediate-release tramadol HCl/acetaminophen in patients with acute pain following total knee replacement. Bin, SI; Chang, N; Cho, SD; Choi, CH; Ha, CW; Kang, SB; Kyung, HS; Lee, JH; Lee, MC; Park, YB; Rhim, HY; Seo, SS, 2015)	0.64
" The incidence of adverse events was comparable between the 2 treatment groups."	( Effectiveness and Safety of Transdermal Buprenorphine Versus Sustained-release Tramadol in Patients With Moderate to Severe Musculoskeletal Pain: An 8-Week, Randomized, Double-Blind, Double-Dummy, Multicenter, Active-controlled, Noninferiority Study. Dai, K; Leng, X; Li, Z; Liu, Y; Lv, H; Yan, X; Yao, C; Zeng, X; Zheng, Y, 2015)	0.64
" In the present work we have revised the efficacy, safety, biological and adverse effects of TrHC, and the added value of developing a novel drug delivery system for topical administration."	( Tramadol hydrochloride: pharmacokinetics, pharmacodynamics, adverse side effects, co-administration of drugs and new drug delivery systems. Andreani, T; Faggio, C; Fangueiro, J; Garcia, ML; Santini, A; Silva, AM; Silva, C; Souto, EB; Vazzana, M, 2015)	1.86
"The purpose of this study was to evaluate patient safety, in terms of adverse events, alterations in blood pressure or oxygen saturation (SpO2) in two routine sedation procedures, with and without intravenous analgesia."	( Safety of adjunct pre-emptive intravenous tramadol with midazolam sedation for third molar surgery. Eriksson, LB; Tegelberg, Å, 2015)	0.68
"The results confirm that pre-emptive intravenous tramadol, administered at 1 mg/kg body weight as an adjunct to midazolam sedation for third molar surgery, offers a safe method."	( Safety of adjunct pre-emptive intravenous tramadol with midazolam sedation for third molar surgery. Eriksson, LB; Tegelberg, Å, 2015)	0.94
" With tramadol's increasing popularity, the goal of this article is to make physicians more alert and aware of this potential side effect associated with tramadol."	( Tramadol, Pharmacology, Side Effects, and Serotonin Syndrome: A Review. Beakley, BD; Kaye, AD; Kaye, AM, )	2.05
" Collected data included socio-demographics, treatment information, incidence of adverse drug reactions (ADRs), numerical rating scale for intensity of pain, EuroQol-5D (EQ-5D) scale, and physician's global impression (PGI) during the 12 week observation period."	( Overall safety profile and effectiveness of tramadol hydrochloride/acetaminophen in patients with chronic noncancer pain in Japanese real-world practice. Fujie, M; Kawai, K; Ogawa, Y; Suzuki, J; Yajima, T; Yokomori, J; Yoshizawa, K, 2015)	0.68
" Along with the increase in their use, there has been an increment in their abuse, and consequently in the reported number of adverse reactions and intoxications."	( Acute administration of tramadol and tapentadol at effective analgesic and maximum tolerated doses causes hepato- and nephrotoxic effects in Wistar rats. Afonso, LP; Barbosa, J; Carvalho, F; Dinis-Oliveira, RJ; Faria, J; Leal, S; Lobo, J; Moreira, R; Queirós, O, 2017)	0.76
"Serious neurological adverse events (NAE) have occurred during treatment with high-dose thiotepa regimens of children with high-risk solid tumours."	( High-dose thiotepa-related neurotoxicity and the role of tramadol in children. Demirdjian, S; Dufour, C; Laplanche, A; Lemare, F; Maritaz, C; Valteau-Couanet, D, 2018)	0.73
" Data were self-reported by patients (pain, adverse events [AEs] and healthcare resources use) and physicians (morphine equivalent daily dose [MEDD] prescribed and suspected adverse drug reaction [ADRs])."	( Health benefits of an adverse events reporting system for chronic pain patients using long-term opioids. Ajo, R; Esteban, MD; Inda, MD; Margarit, C; Muriel, J; Peiró, AM; Planelles, B; Sastre, Y, 2019)	0.51
" In conclusion, Curcumin and/or Gallic acid alleviated the adverse effects caused by tramadol."	( Tramadol-induced hepato- and nephrotoxicity in rats: Role of Curcumin and Gallic acid as antioxidants. Almasmari, AA; El-Banna, SG; Sheweita, SA, 2018)	2.15
" Acetaminophen is a mild analgesic and antipyretic agent, which can cause centrilobular hepatic necrosis in toxic doses, whereas alcohol causes death due to liver diseases."	( Pharmacokinetic changes of tramadol in rats with hepatotoxicity induced by ethanol and acetaminophen in perfused rat liver model. Ardakani, YH; Esmaeili, Z; Ghazi-Khansari, M; Hassanzadeh, G; Lavasani, H; Mohammadi, S; Nezami, A; Rouini, MR, 2019)	0.81
" In the absence of CYP inhibition (trial A), 20 mg desmetramadol and 50 mg tramadol dosed every 6 hours gave equivalent steady-state (+)-M1, similar adverse events, and analgesia significantly greater than placebo, but equal to each other."	( Desmetramadol Has the Safety and Analgesic Profile of Tramadol Without Its Metabolic Liabilities: Consecutive Randomized, Double-Blind, Placebo- and Active Comparator-Controlled Trials. Johnson, MS; Kahn, SJ; Maeda, DY; Schuler, AD; Searle, SL; Webster, LR; Zebala, JA, 2019)	1.27
" Standard-dosage ketoprofen administration resulted in clinically relevant adverse effects."	( Safety and efficacy of reduced dosage ketoprofen with or without tramadol for long-term treatment of osteoarthritis in dogs: a randomized clinical trial. Bianchi, E; Genevois, JP; Lambert, C; Monteiro, BP; Soldani, G; Troncy, E, 2019)	0.75
" Regression models estimated daily milligrams morphine equivalent (MME), daily prescription acetaminophen dose, potentially toxic acetaminophen doses, nonopioid prescription analgesics receipt, emergency room visits, and diagnosed falls, motor vehicle accidents, and hip fractures."	( Response to Propoxyphene Market Withdrawal: Analgesic Substitutes, Doses, and Adverse Events. Hooten, WM; Jeffery, MM; Larochelle, M; Meara, E; Morden, NE; Shah, ND, 2020)	0.56
" Adverse events were rare and not significantly different in exposed versus unexposed groups."	( Response to Propoxyphene Market Withdrawal: Analgesic Substitutes, Doses, and Adverse Events. Hooten, WM; Jeffery, MM; Larochelle, M; Meara, E; Morden, NE; Shah, ND, 2020)	0.56
"The aim of this systematic review and meta-analysis was to appraise clinical evidence of the impact of peritonsillar infiltration of tramadol, on postoperative pain control and the occurrence of adverse effects in children undergoing tonsillectomy."	( Analgesic Efficacy and Safety of Local Infiltration of Tramadol in Pediatric Tonsillectomy Pain: A Systematic Review and Meta-Analysis. Chatzistravou, A; Grosomanidis, V; Kouvelas, D; Papazisis, G; Pourzitaki, C; Tsaousi, GG, 2020)	1.01
" The outcomes of interest were postoperative pain intensity, time to first analgesic demand, rescue analgesic consumption up to 24 hours after intervention, and the occurrence of adverse events."	( Analgesic Efficacy and Safety of Local Infiltration of Tramadol in Pediatric Tonsillectomy Pain: A Systematic Review and Meta-Analysis. Chatzistravou, A; Grosomanidis, V; Kouvelas, D; Papazisis, G; Pourzitaki, C; Tsaousi, GG, 2020)	0.81
"In children undergoing tonsillectomy, peritonsillar infiltration of tramadol is associated with a postoperative analgesic benefit when compared to placebo, with negligible adverse events."	( Analgesic Efficacy and Safety of Local Infiltration of Tramadol in Pediatric Tonsillectomy Pain: A Systematic Review and Meta-Analysis. Chatzistravou, A; Grosomanidis, V; Kouvelas, D; Papazisis, G; Pourzitaki, C; Tsaousi, GG, 2020)	1.04
" Although characterized as having fewer opioid-related adverse events, the longer term safety of tramadol use among older adults has not been thoroughly documented."	( Safety Events Associated with Tramadol Use Among Older Adults with Osteoarthritis. Kraemer, S; Musich, S; Schaeffer, JA; Slindee, L; Wang, SS; Yeh, CS, 2021)	1.13
"To perform the analysis, a comprehensive database consisting of pain relief compounds with information on summary-level of efficacy over time, adverse events and dropout rates was compiled from multiple sources."	( Model-based Meta-analysis to Compare Primary Efficacy-endpoint, Efficacy-time Course, Safety, and Tolerability of Opioids Used in the Management of Osteoarthritic Pain in Humans. Alhaj-Suliman, SO; Milavetz, G; Salem, AK, 2020)	0.56
" It was also found that gastrointestinal adverse events were the most opioid-associated and dosedependent adverse effects."	( Model-based Meta-analysis to Compare Primary Efficacy-endpoint, Efficacy-time Course, Safety, and Tolerability of Opioids Used in the Management of Osteoarthritic Pain in Humans. Alhaj-Suliman, SO; Milavetz, G; Salem, AK, 2020)	0.56
"The current study was performed to study the tramadol HCL toxic effects on the brain, liver, and kidney of adult male rats."	( Neurotoxic, Hepatotoxic and Nephrotoxic Effects of Tramadol Administration in Rats. Afifi, M; Al-Farga, A; Ali, HA; Baeshen, M; Keshta, AT; Makki, AA; Saber, TM, 2020)	1.07
" Regarding the adverse effects of tramadol on different tissues, especially the nervous system and liver tissue, more attentions to tramadol metabolites, their interaction with other drugs, and active agents seem critical."	( ADME and toxicity considerations for tramadol: from basic research to clinical implications. Doostmohammadi, M; Rahimi, HR, 2020)	1.11
" Minor adverse effects appeared to be related to the higher doses of tramadol."	( Efficacy and Safety of Two Fixed-Dose Combinations of Tramadol Hydrochloride and Diclofenac Sodium in Postoperative Dental Pain. Alvarado, F; Desjardins, P; Gil, M; González, M; Guajardo, R, 2020)	1.04
"IV tramadol is superior to IV paracetamol in relieving acute pain of primary dysmenorrhea with a comparable side effect profile."	( Efficacy and Safety of Intravenous Tramadol versus Intravenous Paracetamol for Relief of Acute Pain of Primary Dysmenorrhea: A Randomized Controlled Trial. Abbas, AM; Alalfy, M; AlAmodi, AA; Ali, AS; Fadlalmola, HA; Ghamry, NK; Hamza, M; Islam, Y; Mahmoud, AO; Shareef, MA, 2020)	1.46
" Tramadol group had reported a significantly higher number of adverse events with treatment as compared to placebo but none of them were serious."	( Safety and efficacy of "on-demand" tramadol in patients with premature ejaculation: an updated meta-analysis. Bora, GS; Devana, SK; Mavuduru, RS; Sharma, AP; Sharma, G; Singh, SK; Tyagi, S, )	1.32
"Tramadol appears to be an effective drug for the management of PE with a low propensity for serious adverse events."	( Safety and efficacy of "on-demand" tramadol in patients with premature ejaculation: an updated meta-analysis. Bora, GS; Devana, SK; Mavuduru, RS; Sharma, AP; Sharma, G; Singh, SK; Tyagi, S, )	1.85
" The toxicity profiles of tramadol and tapentadol are similar; however tapentadol is likely to result in less exposure to serotoninergic adverse effects (nausea, vomiting, hypoglycaemia) but cause more opioid adverse effects (constipation, respiratory depression, abuse) than tramadol."	( Tapentadol Versus Tramadol: A Narrative and Comparative Review of Their Pharmacological, Efficacy and Safety Profiles in Adult Patients. Desmeules, J; Piguet, V; Rollason, V; Roulet, L, 2021)	1.26
" Gastrointestinal, cardiovascular, and central nervous system (CNS) adverse events (AEs), and withdrawals were measured for safety."	( Efficacy and Safety of Tramadol for Knee or Hip Osteoarthritis: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials. Lei, G; Li, X; Sha, T; Wang, Y; Wei, J; Xiong, Y; Zeng, C; Zhang, X, 2023)	1.22
" The first study, a noninferiority randomized clinical trial in England, evaluated whether antihypertensive medication reduction is possible without significant changes in systolic blood pressure control or adverse events over the 12-week follow-up (domain: deprescribing)."	( Medication use quality and safety in older adults: 2020 update. Eshetie, TC; Gray, SL; Marcum, ZA; Schmader, KE, 2022)	0.72
"Tramadol is known to cause fewer adverse events (AEs) than other opioids."	( Comparison of Online Patient Reviews and National Pharmacovigilance Data for Tramadol-Related Adverse Events: Comparative Observational Study. Choi, SH; Kwon, JW; Park, S; Song, YK, 2022)	2.39
"This study used 2 data sets, 1 from patients' drug reviews on WebMD (January 2007 to January 2021) and 1 from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS; January 2016 to December 2020)."	( Comparison of Online Patient Reviews and National Pharmacovigilance Data for Tramadol-Related Adverse Events: Comparative Observational Study. Choi, SH; Kwon, JW; Park, S; Song, YK, 2022)	0.95
" Its dose must be commonly monitored according to pain status and to alleviate the appearance of any adverse effects such as renal cellular damage during its excretion."	( 10-Dehydrogingerdione Attenuates Tramadol-Induced Nephrotoxicity by Modulating Renal Oxidative Stress, Inflammation and Apoptosis in Experimental Rats: Role of HO-1 Activation and TLR4/NF-κB/ERK Inhibition. Al-Gabri, NA; Alnomasy, SF; Althafar, ZM; Elkomy, NMIM; Elnagar, GM; Elseweidy, MM; Mahmoud, YK; Shawky, M, 2022)	1
" Adverse events occurred in 80."	( Efficacy and Safety of Tramadol Hydrochloride Twice-Daily Sustained-Release Bilayer Tablets with an Immediate-Release Component for Chronic Pain Associated with Knee Osteoarthritis: A Randomized, Double-Blind, Placebo-Controlled, Treatment-Withdrawal Stud Adachi, T; Jinnouchi, M; Kawai, S; Nakano, H; Ohtani, H; Sakata, M; Sobajima, S, 2022)	1.03
"ESPB was an efficient and safe procedure for postoperative pain management in PCNL."	( Efficiency and Safety of Erector Spinae Plane Block in Percutaneous Nephrolithotomy: A Meta-Analysis Based on Randomized Controlled Trials. Jin, T; Lin, L; Luo, Z; Ma, Y; Xiao, K, 2022)	0.72
" Although superiority to tramadol was not reached, CTC 200 mg BID exposed patients to lower cumulative opioid (tramadol) doses than tramadol (100 mg QID) alone, with fewer treatment-emergent adverse events."	( Efficacy and safety of co-crystal of tramadol-celecoxib (CTC) in acute moderate-to-severe pain after abdominal hysterectomy: A randomized, double-blind, phase 3 trial (STARDOM2). Adeyemi, S; But-Husaim, L; Cebrecos, J; Fettiplace, J; Gascón, N; Langford, R; Morte, A; Ortiz, E; Plata-Salamán, C; Raba, G; Sust, M; Vaqué, A, 2022)	1.3
" The current study aimed to investigate the protective effects of antioxidants (garlic and selenium) against the toxic effects of tramadol on semen characteristics, steroid hormones, the protein expressions of different cytochrome P450 isozymes [CYP 21A2, CYP 19, and 11A1], and on antioxidant enzyme activities in testes of rabbits."	( Antioxidants (selenium and garlic) alleviated the adverse effects of tramadol on the reproductive system and oxidative stress markers in male rabbits. El-Dafrawi, YA; El-Ghalid, OA; Ghoneim, AA; Sheweita, SA; Wahid, A, 2022)	1.16
" Adverse events in ≥10% of patients in the open-label period were constipation (43."	( Efficacy and safety of twice-daily tramadol hydrochloride bilayer sustained-release tablets with an immediate release component for postherpetic neuralgia: Results of a Phase III, randomized, double-blind, placebo-controlled, treatment-withdrawal study. Adachi, T; Fukuuchi, Y; Hasegawa, J; Ito, H; Kawai, S; Nakano, H; Ohtani, H; Sasaki, K, 2023)	1.19
"The aim of this study was to evaluate postoperative analgesia effectiveness and patient-controlled analgesia (PCA)-related adverse events."	( Effectiveness of Sufentanil-Based Patient-Controlled Analgesia Regimen in Children and Incidence of Adverse Events Following Major Congenital Structure Repairs. Liu, F; Xie, D; Zuo, Y, 2023)	0.91
"Primary outcomes were low back pain intensity (0-100 scale) at end of treatment and safety (number of participants who reported any adverse event during treatment)."	( Comparative effectiveness and safety of analgesic medicines for adults with acute non-specific low back pain: systematic review and network meta-analysis. Bagg, MK; Cashin, AG; Day, R; Ferraro, MC; Gustin, SM; Hagstrom, AD; Jones, MD; Leake, HB; Maher, CG; McAuley, JH; McLachlan, AJ; Nikolakopolou, A; O'Connell, NE; Rizzo, RR; Schabrun, S; Sharma, S; Wand, BM; Wewege, MA, 2023)	0.91
"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)	1.22
"Although opioids have been shown to be effective for cancer pain, opioid-induced adverse events (AEs) are common."	( Prevalence of opioid-induced adverse events across opioids commonly used for analgesic treatment in Japan: a multicenter prospective longitudinal study. Arakawa, S; Chiu, SW; Hiratsuka, Y; Hirayama, H; Inoue, A; Ishiki, H; Kosugi, K; Kubo, E; Matsuda, Y; Miyashita, M; Morita, T; Natsume, M; Nishijima, K; Ouchi, K; Sato, M; Satomi, E; Shigeno, T; Shimizu, M; Shimoda, M; Shimoi, T; Tagami, K; Yamaguchi, T; Yokomichi, N, 2023)	0.91
" Tramadol overdose is becoming a health crisis in Egypt and is associated with serious and severe adverse effects."	( Clinical and Laboratory Factors Related to Seizure and Serotonin Toxicity in Tramadol Intoxication: An Egyptian Study. Abdelkawy, K; Abdeshafy, MM; Ali, AA; Elbarbry, F; Elsabaa, RM, 2023)	2.05
"Seizure and serotonin toxicity are severe adverse effects of tramadol overdose that occur in high frequency among young Egyptians."	( Clinical and Laboratory Factors Related to Seizure and Serotonin Toxicity in Tramadol Intoxication: An Egyptian Study. Abdelkawy, K; Abdeshafy, MM; Ali, AA; Elbarbry, F; Elsabaa, RM, 2023)	1.38

Excerpt	Reference	Relevance
" Serum and urine concentrations of tramadol-HCl were determined by gas chromatography-mass spectrometry and gas chromatography, respectively, and the pharmacokinetic evaluation was carried out model-dependently."	( Pharmacokinetics of tramadol and bioavailability of enteral tramadol formulations. 2nd communication: drops with ethanol. Barth, H; Becker, R; Frankus, E; Lintz, W; Schmidt-Böthelt, E, 1998)	0.9
" Serum concentrations of tramadol-HCl were determined by gas chromatography-mass spectrometry and the pharmacokinetic evaluation was carried out model-dependently."	( Pharmacokinetics of tramadol and bioavailability of enteral tramadol formulations. 3rd Communication: suppositories. Barth, H; Lintz, W; Osterloh, G; Schmidt-Böthelt, E, 1998)	0.93
" Applicability of the method was demonstrated by a pharmacokinetic study in normal volunteers who received 100 mg of tramadol by the intravenous route."	( Enantiomeric separation of tramadol and its active metabolite in human plasma by chiral high-performance liquid chromatography: application to pharmacokinetic studies. Calahorra, B; Campanero, MA; Honorato, J; Troconiz, IF; Valle, M, 1999)	0.81
"The relationship between the dose and the pharmacokinetic characteristics."	( Pharmacokinetic properties of tramadol sustained release capsules. 1st communication: investigation of dose linearity. Amschler, S; Momberger, H; Raber, M; Schulz, HU; Schürer, M, 1999)	0.59
" Statistical analysis of AUC(0-infinity) and Cmax after logarithmic transformation yielded bioequivalence of tramadol sustained release capsules with and without concomitant food intake."	( Pharmacokinetic properties of tramadol sustained release capsules. 2nd communication: investigation of relative bioavailability and food interaction. Bias-Imhoff, U; Momberger, H; Raber, M; Schulz, HU; Schürer, M, 1999)	0.8
" Pharmacokinetic application with intravenous tramadol in humans and rabbits revealed that tramadol followed a two-compartment open model with one distribution phase and one elimination phase."	( Determination of tramadol by capillary gas chromatography with flame ionization detection. Application to human and rabbit pharmacokinetic studies. Ho, CM; Ho, ST; Li, JH; Liaw, WJ; Wan, JJ, 1999)	0.9
" The pharmacokinetic evaluation was carried out model-dependently after previous selection of the optimal model by means of the Akaike information criterion; solely the extent of bioavailability was calculated model-independently."	( Pharmacokinetics of tramadol and bioavailability of enteral tramadol formulations. 4th communication: drops (without ethanol). Becker, R; Gerloff, J; Lintz, W; Terlinden, R, 2000)	0.63
" Pharmacodynamic endpoints evaluated were respiratory depression, measured as the change in arterial blood pCO(2), pO(2), and pH levels; and antinociception, measured by the tail-flick technique."	( Pharmacokinetic-pharmacodynamic modeling of the antinociceptive effects of main active metabolites of tramadol, (+)-O-desmethyltramadol and (-)-O-desmethyltramadol, in rats. Calvo, R; Garrido, MJ; Pavón, JM; Trocóniz, IF; Valle, M, 2000)	0.52
" All pharmacokinetic variables were evaluated using a non-compartmental model."	( Pharmacokinetics of tramadol in children after i.v. or caudal epidural administration. Booker, PD; Lintz, W; Murray, A; Murthy, BV; Pandya, KS; Terlinden, R, 2000)	0.63
" The differences were significant in the main pharmacokinetic parameters between (+)-trans-T and (-)-trans-T except Tmax."	( Pharmacokinetics of enantiomers of trans-tramadol and its active metabolite, trans-O-demethyltramadol, in human subjects. Hou, YN; Liu, HC; Liu, TJ; Yang, YY, 2001)	0.58
" The pharmacokinetic stereoselectivity of M1 was different among human subjects."	( Pharmacokinetics of enantiomers of trans-tramadol and its active metabolite, trans-O-demethyltramadol, in human subjects. Hou, YN; Liu, HC; Liu, TJ; Yang, YY, 2001)	0.58
"046) longer mean serum half-life of tramadol than subjects of the normal or the heterozygous group (Kruskal-Wallis test)."	( Correlation of tramadol pharmacokinetics and CYP2D6*10 genotype in Malaysian subjects. Gan, SH; Ismail, R; Wan Adnan, WA; Wan, Z, 2002)	0.94
"This report describes a pharmacokinetic study and a clinical study of three different formulations of oral tramadol: once-daily tramadol tablets 150 and 200 mg, and normal release tramadol capsules 50 mg 8-hourly."	( A comparison of the pharmacokinetics, clinical efficacy, and tolerability of once-daily tramadol tablets with normal release tramadol capsules. Bodalia, B; Cousens, L; McDonald, CJ; O'Brien, C; Smith, KJ, 2003)	0.75
" As the serum concentration profile and pharmacokinetic parameters in young children are not known via this route, we studied 24 healthy ASA 1 children to determine those parameters."	( Pharmacokinetics of oral tramadol drops for postoperative pain relief in children aged 4 to 7 years--a pilot study. Payne, KA; Roelofse, JA; Shipton, EA, 2002)	0.62
" All pharmacokinetic parameters but Tmax of the two enantiomers of trans-T were significantly different in both sex rats."	( Gender-related differences in pharmacokinetics of enantiomers of trans-tramadol and its active metabolite, trans-O-demethyltramadol, in rats. Jin, SM; Liu, HC; Wang, YL, 2003)	0.55
" The values of Cmax for the enantiomers of trans-T and M1, and AUC0- infinity for (-)-trans T, (+)-M1, and (-)-M1 were higher in females than in males."	( Pharmacokinetics of the enantiomers of trans-tramadol and its active metabolite, trans-O-demethyltramadol, in healthy male and female chinese volunteers. Hong-Yuan, X; Hui-Chen, L; Jian-Fang, L; Ming, D; Na, W; Yang, Y, 2004)	0.58
"To compare the pharmacokinetic profile of a new modified release formulation of tramadol (Tramadol LP 200 mg, SMB Technology, Marche-en-Famenne, Belgium) with that of an immediate release capsule (Topalgic) 50 mg, Grünenthal, Aachen, Germany) after single and multiple dosing and to assess the potential effect of food on its relative bioavailability."	( Pharmacokinetic evaluation of a new oral sustained release dosage form of tramadol. De Niet, S; Lebrun, S; Malonne, H; Sereno, A; Sonet, B; Streel, B; Vanderbist, F, 2004)	0.78
"Tramadol had a significantly lower Cmax and longer Tmax than the conventional formulation."	( Pharmacokinetic evaluation of a new oral sustained release dosage form of tramadol. De Niet, S; Lebrun, S; Malonne, H; Sereno, A; Sonet, B; Streel, B; Vanderbist, F, 2004)	2
" Furthermore, its pharmacokinetic profile is not affected by the intake of food."	( Pharmacokinetic evaluation of a new oral sustained release dosage form of tramadol. De Niet, S; Lebrun, S; Malonne, H; Sereno, A; Sonet, B; Streel, B; Vanderbist, F, 2004)	0.55
" This method was successfully used to investigate plasma concentration of enantiomers of tramadol, O-desmethyltramadol and N-desmethyltramadol in a pharmacokinetic study."	( Simultaneous stereoselective analysis of tramadol and its primary phase I metabolites in plasma by liquid chromatography. Application to a pharmacokinetic study in humans. Azanza, JR; Campanero, MA; García-Quetglas, E; Sádaba, B, 2004)	0.81
" The pharmacokinetic parameters derived from the model indicate that a low variability was present."	( Pharmacokinetics of rectal tramadol in postoperative paediatric patients. Bubbers, S; Burggraaf, J; Schoemaker, RC; van Heel, IR; van Meurs, AH; Vermeij, P; Zwaveling, J, 2004)	0.62
" Even although the galenics of both products are far different, statistical analysis of pharmacokinetic parameters allows concluding bioequivalence, not only for the parent molecule (tramadol), but also for its active metabolite O-desmethyl tramadol."	( Pharmacokinetic assessment of a fast-release orodispersible tramadol tablet compared to a conventional tramadol capsule. Díez, MC; Tagarro, I; Vauzelle-Kervroedan, F, 2004)	0.76
"Although the kinetic behaviour of tramadol has been described, the present study is the first to our knowledge, to report specifically on the population pharmacokinetic modelling of tramadol hydrochloride."	( Population pharmacokinetic modelling of tramadol with application of the NPEM algorithms. Gan, SH; Ismail, R; Jelliffe, RW; Wan Adnan, WA; Zulmi, W, 2004)	0.87
"The parametric Iterative Two-stage Bayesian Population Model (IT2B) program followed by the Non-parametric Expectation Maximization Population Model (NPEM2) program was used to determine population pharmacokinetic parameter values of tramadol in 138 postoperative orthopaedic Malaysian patients."	( Population pharmacokinetic modelling of tramadol with application of the NPEM algorithms. Gan, SH; Ismail, R; Jelliffe, RW; Wan Adnan, WA; Zulmi, W, 2004)	0.77
"The one-compartmental model pharmacokinetic parameters--volume of distribution (Vd), elimination rate constant (kel) and the total clearance rates (ClT)--found were: mean Vd = 167."	( Population pharmacokinetic modelling of tramadol with application of the NPEM algorithms. Gan, SH; Ismail, R; Jelliffe, RW; Wan Adnan, WA; Zulmi, W, 2004)	0.59
" The method described was applied to a pharmacokinetic study of intravenous tramadol injections in rabbits."	( Investigation of the pharmacokinetics and determination of tramadol in rabbit plasma by a high-performance liquid chromatography-diode array detector method using liquid-liquid extraction. Celebi, F; Kadioğlu, Y; Küçük, A, 2005)	0.8
"The main objective of the present study was to provide information on whether static and dynamic pupillometry can be used for pharmacodynamic profiling, particularly when investigating opioid-like drugs, such as tramadol."	( The effects of tramadol on static and dynamic pupillometry in healthy subjects--the relationship between pharmacodynamics, pharmacokinetics and CYP2D6 metaboliser status. Fliegert, F; Göhler, K; Kurth, B, 2005)	0.87
" The reason for this could largely be explained with the aid of the metaboliser status and the pharmacokinetic properties of tramadol."	( The effects of tramadol on static and dynamic pupillometry in healthy subjects--the relationship between pharmacodynamics, pharmacokinetics and CYP2D6 metaboliser status. Fliegert, F; Göhler, K; Kurth, B, 2005)	0.89
"The aim of the present study was to investigate the pharmacokinetic profile of tramadol hydrochloride in neonates, born from mothers who underwent analgesia with tramadol for the relief of labour pain."	( Different pharmacokinetics of tramadol in mothers treated for labour pain and in their neonates. Claahsen-van der Grinten, HL; Kollée, LA; Sporken, JM; van den Berg, PP; Verbruggen, I, 2005)	0.84
" Another venous blood sample was drawn from each neonate, and at the same time from its mother, at 1, 2, 3, 6 or 12 h post-partum, providing the data for a population pharmacokinetic evaluation of tramadol and its metabolite M1."	( Different pharmacokinetics of tramadol in mothers treated for labour pain and in their neonates. Claahsen-van der Grinten, HL; Kollée, LA; Sporken, JM; van den Berg, PP; Verbruggen, I, 2005)	0.81
"The impact of CYP2D6 phenotype on tramadol pharmacokinetics was similar after single oral, multiple oral and intravenous administration displaying significant pharmacokinetic differences between EMs and PMs of (+)-tramadol, (-)-tramadol, -(+)-M1 and (-)-M1."	( Enantioselective pharmacokinetics of tramadol in CYP2D6 extensive and poor metabolizers. Brøsen, K; Damkier, P; Pedersen, RS, 2006)	0.89
" A simultaneous pharmacokinetic model describing the plasma concentration-curves of the generated metabolites and the parent compounds after intravenous and oral drug administration is developed and presented."	( Stereoselective pharmacokinetic analysis of tramadol and its main phase I metabolites in healthy subjects after intravenous and oral administration of racemic tramadol. Azanza, JR; Campanero, MA; Cardenas, E; García Quetglas, E; Sádaba, B, 2007)	0.6
" In rats and in mice, intraperitoneal microdialysis sampling gets reliable pharmacokinetic results without taking blood."	( Peritoneal microdialysis in freely moving rodents: an alternative to blood sampling for pharmacokinetic studies in the rat and the mouse. Beier, H; Kaiser, K; Langhans, M; Malmendier, K; Sluijsmans, I; Weiher, J, 2007)	0.34
" The pharmacokinetic parameters were estimated from plasma concentrations of the enantiomers of tramadol and their main phase I metabolites, O-desmethyltramadol (M1) and N-desmethyltramadol (M2)."	( Pharmacokinetics of tramadol enantiomers and their respective phase I metabolites in relation to CYP2D6 phenotype. Azanza, JR; Campanero, MA; García-Quetglas, E; Gil, I; Muñoz, MJ; Sádaba, B, 2007)	0.88
" Epinephrine showed a good correlation with the pharmacokinetics of the opioid component of tramadol, (+)-M1 and was found to be useful for its pharmacodynamic profiling."	( Pharmacokinetics of tramadol enantiomers and their respective phase I metabolites in relation to CYP2D6 phenotype. Azanza, JR; Campanero, MA; García-Quetglas, E; Gil, I; Muñoz, MJ; Sádaba, B, 2007)	0.88
" Samples were analyzed using chiral chromatography, and pharmacokinetic parameters (mean +/- SD) were estimated by noncompartmental methods."	( Route-dependent stereoselective pharmacokinetics of tramadol and its active O-demethylated metabolite in rats. Elliott, K; Mehvar, R; Parasrampuria, R; Vuppugalla, R, 2007)	0.59
"This pharmacokinetic analysis supports switching patients from a total daily dose of tramadol IR 200 or 300 mg directly to tramadol ER 200 and 300 mg once daily, respectively."	( Pharmacokinetic model and simulations of dose conversion from immediate- to extended-release tramadol. Brett, V; Danyluk, AP; Moskovitz, BL; Murthy, BP; Skee, DM; Vorsanger, GJ, 2007)	0.78
" Although age-related differences in pharmacologic responsiveness are to be expected, the pharmacodynamic and pharmacokinetic (PK) properties of tramadol have not been systematically compared between patients of various ages."	( Pharmacokinetic and pharmacodynamic properties of tramadol IR and SR in elderly patients: a prospective, age-group-controlled study. Kager, I; Likar, R; Molnar, M; Sittl, R; Wittels, M; Ziervogel, G, 2006)	0.79
" Tramadol is a racemic mixture of 2 enantiomers that have comparable pharmacokinetic profile and this lack of difference is also observed with their main active metabolite, O-demethyl tramadol (M1)."	( [Pharmacokinetics of tramadol in children]. Habre, W; Saudan, S, 2007)	1.57
" The mean total clearance (CL) predicted by the model was lower (19 L/h) and the half-life longer (5."	( Impact of CYP2D6 genetic polymorphism on tramadol pharmacokinetics and pharmacodynamics. Gan, SH; Ismail, R; Wan Adnan, WA; Zulmi, W, 2007)	0.61
" Pharmacokinetic parameters were derived using noncompartmental methods."	( Pharmacokinetics and dose proportionality of three Tramadol Contramid OAD tablet strengths. Bouchard, S; Dupain, T; El-Jammal, A; Gaulin, D; Karhu, D, 2007)	0.59
" The related pharmacokinetic parameters such as C(max), T(max), AUC((0-t)), AUC((0-infinity)), T(1/2) and Cl/F were calculated and compared between the two genders."	( Pharmacokinetics of tramadol and its three main metabolites in healthy male and female volunteers. Ardakani, YH; Rouini, MR, 2007)	0.66
" administration, the apparent volume of distribution of the central compartment, the apparent volume of distribution at steady-state, the clearance, and the terminal half-life (mean +/- SEM) were 1553+/-118 mL/kg, 3103+/-132 mL/kg, 20."	( Pharmacokinetics of tramadol, and its metabolite O-desmethyl-tramadol, in cats. Ilkiw, JE; Pypendop, BH, 2008)	0.67
" The concentration of tramadol and its M1 metabolite were determined in the obtained plasma samples by use of an LC/MS/MS method and were used for pharmacokinetic calculations."	( Pharmacokinetics of tramadol in horses after intravenous, intramuscular and oral administration. Britzi, M; Eytan, B; Lifschitz, T; Shilo, Y; Soback, S; Steinman, A, 2008)	0.98
" In conclusion, pharmacokinetic differences between EMs and UMs were smaller than expected; nevertheless, UMs were more sensitive to tramadol than EMs."	( Effects of the CYP2D6 gene duplication on the pharmacokinetics and pharmacodynamics of tramadol. Bauer, S; Brockmöller, J; Keulen, JT; Kirchheiner, J; Roots, I, 2008)	0.77
" The findings suggest that the SR formulation of tramadol may not have suitable pharmacokinetic characteristics to be administered once-a-day as an effective and safe treatment for pain in the dog."	( Pharmacokinetic evaluation of tramadol and its major metabolites after single oral sustained tablet administration in the dog: a pilot study. Giorgi, M; Kowalski, C; Lebkowska-Wieruszewska, B; Saccomanni, G, 2009)	0.9
" On the basis of computer-generated pharmacokinetic models, one can easily transition patients who are receiving short-acting tramadol for chronic/persistent pain to tramadol ER, by calculating the current total daily dose of short-acting tramadol and starting tramadol ER at the nearest lower 100-mg-dose increment."	( Extended-release Tramadol (ULTRAM ER): a pharmacotherapeutic, pharmacokinetic, and pharmacodynamic focus on effectiveness and safety in patients with chronic/persistent pain. Barkin, RL, )	0.68
"The authors have studied the pharmacokinetic profile of oral tramadol (50 mg) capsule in 20 patients with liver carcinoma (10 with primary carcinoma on top of chronic hepatitis C and 10 with secondary metastatic liver malignancy as a result of other primary) compared with 10 healthy controls."	( Pharmacokinetics of oral tramadol in patients with liver cancer. Abd El-Rahman, AM; Fares, KM; Fouad, IA; Kotb, HI; Mostafa, MG, )	0.68
" Also, a significant difference in Cmax and Tmax was found between patients with malignant liver and control."	( Pharmacokinetics of oral tramadol in patients with liver cancer. Abd El-Rahman, AM; Fares, KM; Fouad, IA; Kotb, HI; Mostafa, MG, )	0.43
" Mean +/- SD half-life of tramadol after administration was 145."	( Pharmacokinetics of orally administered tramadol in domestic rabbits (Oryctolagus cuniculus). Cox, SK; Greenacre, CB; Souza, MJ, 2008)	0.91
" The pharmacokinetic behaviour of tramadol in rat plasma and cerebrospinal fluid (CSF) after intranasal administration was determined and compared with those after intravenous and oral administration."	( Pharmacokinetics of tramadol in rat plasma and cerebrospinal fluid after intranasal administration. Chai, X; Chen, Q; He, N; Pi, J; Tao, T; Wu, J; Zhao, Y, 2008)	0.95
" Pharmacodynamic evaluations were performed at the time of patient sampling and included assessment of sedation, and evaluation for depression of heart and respiratory rates."	( Pharmacokinetics of intravenous tramadol in dogs. Clark, CR; Dowling, PM; Duke, T; Livingston, A; McMillan, CJ; Taylor, SM; Terlinden, R, 2008)	0.63
" The clinical efficacy and pharmacokinetic profile of intravenous (i."	( Pharmacokinetics and efficacy of intravenous and extradural tramadol in dogs. Beccaglia, M; Cagnardi, P; Gallo, M; Isola, M; Montesissa, C; Ravasio, G; Vettorato, E; Villa, R; Zonca, A, 2010)	0.6
" The aim of this study was to develop a population pharmacokinetic model for the (+)- and (-)-enantiomers of tramadol and its O-demethyl tramadol metabolite (M1) in children."	( Population pharmacokinetics of the two enantiomers of tramadol and O-demethyl tramadol after surgery in children. Bressolle, F; Capdevila, X; Dadure, C; Khier, S; Ouaki, J; Rochette, A, 2009)	0.81
"To compare the rectal and I/V administration of tramadol in dogs, to assess both its pharmacokinetic properties and absolute bioavailability."	( Pharmacokinetics of tramadol and its major metabolites following rectal and intravenous administration in dogs. Del Carlo, S; Giorgi, M; Kowalski, CJ; Saccomanni, G; Łebkowska-Wieruszewska, B, 2009)	0.93
"In the dog, rectal pharmaceutical formulation of tramadol would have a different pharmacokinetic behaviour than in humans."	( Pharmacokinetics of tramadol and its major metabolites following rectal and intravenous administration in dogs. Del Carlo, S; Giorgi, M; Kowalski, CJ; Saccomanni, G; Łebkowska-Wieruszewska, B, 2009)	0.93
"The aim of the present paper was to test the oral administration of oral immediate release capsules of tramadol in dogs, to asses both its pharmacokinetic properties and its urine profile."	( Pharmacokinetic and urine profile of tramadol and its major metabolites following oral immediate release capsules administration in dogs. Del Carlo, S; Giorgi, M; Kowalski, CJ; Saccomanni, G; Łebkowska-Wieruszewska, B, 2009)	0.84
"The determination of the pharmacokinetic parameters of tramadol in plasma and a better characterization of its metabolites after oral administration to horses is necessary to design dosage regimens to achieve target plasma concentrations that are associated with analgesia."	( Determination of oral tramadol pharmacokinetics in horses. Cox, S; Doherty, T; Villarino, N, 2010)	0.92
"The main pharmacokinetic parameters of tramadol and its metabolite O-demethyltramadol (M(1)) in groups 1 and 2 were not significantly different."	( Relationship of CYP2D6 genetic polymorphisms and the pharmacokinetics of tramadol in Chinese volunteers. Guo, Y; Li, Q; Wang, R; Wang, S; Wen, S; Xu, L, 2010)	0.86
" The pharmacokinetic profile of the drug and its O-desmethyl metabolite were determined in 8 animals (4 males), while intraoperative effects and postoperative analgesia, estimated by subjective pain score (0-24), were evaluated in all."	( Pharmacokinetics, intraoperative effect and postoperative analgesia of tramadol in cats. Beccaglia, M; Cagnardi, P; Carli, S; Fonda, D; Gallo, M; Luvoni, GC; Ravasio, G; Vettorato, E; Villa, R; Zonca, A, 2011)	0.6
"Tramadol (M) is metabolized by O-demethylation (cytochrome P450 [CYP] 2D6) to the pharmacodynamic active metabolite O-demethyl tramadol (M1)."	( Developmental pharmacology of tramadol during infancy: ontogeny, pharmacogenetics and elimination clearance. Allegaert, K; Rochette, A; Veyckemans, F, 2011)	2.1
"A pooled pharmacokinetic analysis of earlier reported time-concentration profiles in neonates and infants was performed with subsequent simulation of the impact of ontogeny, polymorphisms and renal elimination clearance during infancy."	( Developmental pharmacology of tramadol during infancy: ontogeny, pharmacogenetics and elimination clearance. Allegaert, K; Rochette, A; Veyckemans, F, 2011)	0.66
" The pharmacokinetic cross-over study was carried out on 6 healthy male beagle dogs."	( Pharmacokinetics of tramadol and metabolites after injective administrations in dogs. Del Carlo, S; Giorgi, M; Kowalski, CJ; Saccomanni, G; Łebkowska-Wieruszewska, B, 2010)	0.68
" The method developed and validated here was applied to a pharmacokinetic study in rats."	( Simultaneous analysis of tramadol, O-desmethyltramadol, and N-desmethyltramadol enantiomers in rat plasma by high-performance liquid chromatography-tandem mass spectrometry: application to pharmacokinetics. Carvalho, TM; De Moraes, NV; Godoy, AL; Lanchote, VL; Marques, MP; Martinez, EZ, 2011)	0.67
"The aim of this investigation was to demonstrate that nonlinear mixed-effects population pharmacokinetic (PK) modeling can be used to evaluate data from studies of drug transport/excretion into human milk and hence to estimate infant exposure."	( Population pharmacokinetic modeling of tramadol and its O-desmethyl metabolite in plasma and breast milk. Ilett, KF; Paech, MJ; Page-Sharp, M; Salman, S; Sy, SK, 2011)	0.64
" The pharmacokinetic parameters of tramadol and M1 in plasma were examined following intravenous and intramuscular administration to six healthy male llamas."	( Pharmacokinetics of intravenous and intramuscular tramadol in llamas. Cox, S; Doherty, T; Martin-Jimenez, T; van Amstel, S, 2011)	0.9
"The aim of this study was to explore the pharmacokinetic profiles of the new ER tramadol/acetaminophen fixed-dose combination and compare them with those of a conventional immediate-release (IR) formulation after multiple dosing as a Phase I clinical exploratory trial."	( Pharmacokinetics of extended-release versus conventional tramadol/acetaminophen fixed-dose combination tablets: an open-label, 2-treatment, multiple-dose, randomized-sequence crossover study in healthy korean male volunteers. Cho, JY; Chung, YJ; Jang, IJ; Kim, TE; Shin, HS; Shin, SG; Yi, S; Yoon, SH; Yu, KS, 2011)	0.84
" Tramadol and acetaminophen concentrations in plasma were determined simultaneously using LC-MS/MS, and the pharmacokinetic properties were analyzed by noncompartmental method."	( Pharmacokinetics of extended-release versus conventional tramadol/acetaminophen fixed-dose combination tablets: an open-label, 2-treatment, multiple-dose, randomized-sequence crossover study in healthy korean male volunteers. Cho, JY; Chung, YJ; Jang, IJ; Kim, TE; Shin, HS; Shin, SG; Yi, S; Yoon, SH; Yu, KS, 2011)	1.52
" Pharmacokinetic parameters were calculated."	( Pharmacokinetics of tramadol and its major metabolites in alpacas following intravenous and oral administration. Boothe, DM; Duran, SH; Edmondson, MA; Ravis, WR; Stewart, AJ, 2012)	0.7
" The plasma concentration-time course of tramadol was measured by high-performance liquid chromatography and the pharmacokinetic estimated."	( Pharmacokinetics of tramadol in a diverse healthy Chinese population. Guo, T; Li, XL; Su, XY; Wang, YH; Xia, DY; Zhao, LS, 2012)	0.97
" Tramadol is thought to have limited abuse potential compared to mu opioid agonists, but laboratory data indicate that it shares some of their pharmacodynamic effects."	( Pharmacodynamic profile of tramadol in humans: influence of naltrexone pretreatment. Craig, LB; Lofwall, MR; Nuzzo, PA; Siegel, AJ; Stoops, WW; Walsh, SL, 2012)	1.59
"This study evaluated the effect of mu opioid receptor blockade with naltrexone on the pharmacodynamic action of tramadol in humans."	( Pharmacodynamic profile of tramadol in humans: influence of naltrexone pretreatment. Craig, LB; Lofwall, MR; Nuzzo, PA; Siegel, AJ; Stoops, WW; Walsh, SL, 2012)	0.89
" Pharmacodynamic effects were measured before and for 7 h after initial drug administration."	( Pharmacodynamic profile of tramadol in humans: influence of naltrexone pretreatment. Craig, LB; Lofwall, MR; Nuzzo, PA; Siegel, AJ; Stoops, WW; Walsh, SL, 2012)	0.68
" Pharmacodynamic study was performed in rat after intravenous administration."	( Protein functionalized tramadol-loaded PLGA nanoparticles: preparation, optimization, stability and pharmacodynamic studies. Lalan, M; Lalani, J; Misra, A; Rathi, M, 2013)	0.7
" For the 3, 6, and 9 mg/kg dose groups, Cmax , Tmax, and the t1/2λ were 43."	( Pharmacokinetics and pharmacodynamics of tramadol in horses following oral administration. Corado, CR; Knych, HK; McKemie, DS; Sams, R; Scholtz, E, 2013)	0.66
" Depending on the dose administered, the tramadol clearance, volume of distribution and half-life ranged from 24."	( Pharmacokinetics and selected pharmacodynamic effects of tramadol following intravenous administration to the horse. Corado, CR; Knych, HK; McKemie, DS; Steffey, EP, 2013)	0.9
"The paper aims to explore the studying method for the pharmacokinetics of drugs in target organs, the pharmacokinetic process of tramadol hydrochloride in the extracellular fluid of frontal cortex (FrCx) of mice was investigated."	( [Pharmacokinetics of tramadol hydrochloride in the extracellular fluid of mouse frontal cortex studied by in vivo microdialysis]. Fang, H; Hong, ZY; Ma, ZQ; Tao, F; Xu, T, 2013)	0.91
" Pharmacokinetic analyses were performed using non-compartmental methods."	( Effect of the cytochrome P450 2D6*10 genotype on the pharmacokinetics of tramadol in post-operative patients. Cai, L; Cai, XJ; Jiang, B; Lv, XQ; Wang, GX; Xu, J; Xu, YY; Zhang, XC, 2014)	0.63
" The association between genetic polymorphisms in CYP2D6, OPRM1 and ABCB1 and pharmacokinetic and pharmacodynamic properties of TRA was studied."	( Pharmacogenetic aspects of tramadol pharmacokinetics and pharmacodynamics after a single oral dose. Bastami, S; Haage, P; Kronstrand, R; Kugelberg, FC; Uppugunduri, S; Zackrisson, AL, 2014)	0.7
" The objective of this study was to determine the pharmacokinetic parameters of tramadol and its primary metabolite, O-desmethyltramadol (M1), after oral administration of tramadol hydrochloride (HCl) in African penguins (Spheniscus demersus)."	( Pharmacokinetics of tramadol and its primary metabolite O-desmethyltramadol in African penguins (Spheniscus demersus). Bronson, E; Cox, SK; Kilburn, JJ; Kottyan, J; Wack, AN, 2014)	0.95
"Patients with T1DM showed reduced Cmax of both tramadol enantiomers."	( Effects of type 1 and type 2 diabetes on the pharmacokinetics of tramadol enantiomers in patients with neuropathic pain phenotyped as cytochrome P450 2D6 extensive metabolizers. de Moraes, NV; Lanchote, VL; Lauretti, GR, 2014)	0.9
" Pharmacokinetic parameters were derived using a non-compartmental approach."	( Pharmacokinetics of tramadol after subcutaneous administration in a critically ill population and in a healthy cohort. Chapman, MJ; Dooney, NM; Ludbrook, GL; O'Connor, SN; Ong, J; Ramkumar, T; Somogyi, AA; Sundararajan, K; Upton, RN, 2014)	0.73
"This study aimed to develop a population pharmacokinetic model for tramadol that combines different input rates with disposition characteristics."	( Population pharmacokinetic modelling of tramadol using inverse Gaussian function for the assessment of drug absorption from prolonged and immediate release formulations. Brvar, N; Grabnar, I; Mateović-Rojnik, T, 2014)	0.91
"The serum pharmacokinetic profile and urinary excretion of tramadol and its metabolites (O-desmethyltramadol [M1], N-desmethyltramadol [M2] and N,O-desmethyltramadol [M5]) was investigated in a multidrug anaesthetic and analgesic approach for orchiectomy in horses."	( Clinical pharmacokinetics of tramadol and main metabolites in horses undergoing orchiectomy. Cagnardi, P; Ferraresi, C; Pecile, A; Ravasio, G; Villa, R; Zani, DD; Zonca, A, 2014)	0.94
" A population pharmacokinetic analysis was performed using a two-compartment model for tramadol and two additional M1 compartments."	( Tramadol and o-desmethyl tramadol clearance maturation and disposition in humans: a pooled pharmacokinetic study. Allegaert, K; Anderson, BJ; Beier, H; de Hoon, JN; Holford, N; Holford, S; Pedersen, RS; Rochette, A; Stamer, U; Stuber, F; Trocóniz, IF, 2015)	2.08
" Noncompartmental pharmacokinetic analysis was performed."	( Pharmacokinetics of tramadol following intravenous and oral administration in male rhesus macaques (Macaca mulatta). Christe, KL; Kelly, KR; Pypendop, BH, 2015)	0.74
" Terbinafine increased the peak concentration (C max) of tramadol by 53 % (P < 0."	( Effects of terbinafine and itraconazole on the pharmacokinetics of orally administered tramadol. Backman, JT; Hagelberg, NM; Laine, K; Neuvonen, PJ; Olkkola, KT; Saari, TI; Saarikoski, T; Scheinin, M, 2015)	0.89
" This study aimed to evaluate the pharmacokinetic profiles of an SR 75-mg tramadol/650-mg acetaminophen formulation after a single dose compared with an immediate release (IR) 37."	( An assessment of the pharmacokinetics of a sustained-release formulation of a tramadol/acetaminophen combination in healthy subjects. Chae, SW; Im, YJ; Jeon, JY; Kim, EY; Kim, MG; Kim, Y; Oh, DJ; Shin, DH; Yoo, JS, 2015)	0.88
"Two clinical trials were conducted: (1) an open-label, randomized, 3-period, 3-treatment, crossover study to assess the pharmacokinetic SR (one 75-mg tramadol/650-mg acetaminophen combination tablet) formulation profiles after a single dose and IR (one 37."	( An assessment of the pharmacokinetics of a sustained-release formulation of a tramadol/acetaminophen combination in healthy subjects. Chae, SW; Im, YJ; Jeon, JY; Kim, EY; Kim, MG; Kim, Y; Oh, DJ; Shin, DH; Yoo, JS, 2015)	0.84
" The metabolite M1 was formed in both the treatment groups, showing similar pharmacokinetic trends, although the amount of M1 was significantly higher (20%) in the hindlimb vs."	( Pharmacokinetic/pharmacodynamic assessments of 10 mg/kg tramadol intramuscular injection in yellow-bellied slider turtles (Trachemys scripta scripta). De Vito, V; Demontis, MP; Giorgi, M; Owen, H; Salvadori, M; Varoni, MV, 2015)	0.66
" After oral administration, the half-life of tramadol administered at 5 and 10 mg/kg was 20."	( PHARMACOKINETICS OF TRAMADOL AND O-DESMETHYLTRAMADOL IN LOGGERHEAD SEA TURTLES (CARETTA CARETTA). Cox, S; Hupp, A; Kaylor, M; Nelson, SE; Norton, TM; Sladky, KK; Thomas, R, 2015)	1
" Pharmacokinetic parameters fitted a two- and a non-compartmental model for tramadol and M1, respectively."	( Pharmacokinetics and antinociceptive effects of tramadol and its metabolite O-desmethyltramadol following intravenous administration in sheep. Bortolami, E; De Benedictis, GM; Della Rocca, G; Di Salvo, A; Giorgi, M; Isola, M; Kim, TW, 2015)	0.9
"This paper focuses on the retrospective evaluation of physiologically based pharmacokinetic (PBPK) techniques used to mechanistically predict clearance throughout pediatric life."	( Physiologically Based Pharmacokinetic Predictions of Tramadol Exposure Throughout Pediatric Life: an Analysis of the Different Clearance Contributors with Emphasis on CYP2D6 Maturation. Allegaert, K; Annaert, P; Boussery, K; Cuyckens, F; Mannens, G; Michelet, R; Snoeys, J; T'jollyn, H; Van Bocxlaer, J; Van Peer, A; Vermeulen, A, 2015)	0.67
" Blood samples were collected for pharmacokinetic analysis of study drugs and their metabolites over an 8-hour period beginning after the second dose of the study medication."	( Pharmacokinetics of hydrocodone and tramadol administered for control of postoperative pain in dogs following tibial plateau leveling osteotomy. Benitez, ME; KuKanich, B; McMurphy, R; Roush, JK, 2015)	0.69
" The terminal half-life for hydrocodone was 15."	( Pharmacokinetics of hydrocodone and tramadol administered for control of postoperative pain in dogs following tibial plateau leveling osteotomy. Benitez, ME; KuKanich, B; McMurphy, R; Roush, JK, 2015)	0.69
" Pharmacodynamic studies are warranted to determine if tramadol provides analgesic effects in this species."	( PHARMACOKINETICS OF TRAMADOL HYDROCHLORIDE AND ITS METABOLITE O-DESMETHYLTRAMADOL FOLLOWING A SINGLE, ORALLY ADMINISTERED DOSE IN CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS). Barbosa, L; Boonstra, JL; Cox, SK; Gulland, FM; Johnson, SP; Martin-Jimenez, T; Van Bonn, WG, 2015)	0.99
" Samples were analyzed with LC-MS/MS and the pharmacokinetic correlations between matrices were investigated."	( First report on the pharmacokinetics of tramadol and O-desmethyltramadol in exhaled breath compared to plasma and oral fluid after a single oral dose. Beck, O; Meyer, MR; Rosenborg, S; Stenberg, M, 2015)	0.68
"Tramadol is frequently used in geriatric patients; however, pharmacokinetic (PK) publications on tramadol and O-desmethyltramadol (ODM) in elderly patients are rare."	( Pharmacokinetics of Tramadol and O-Desmethyltramadol Enantiomers Following Administration of Extended-Release Tablets to Elderly and Young Subjects. Bouchard, S; Fradette, C; Mouksassi, MS; Skinner-Robertson, S; Varin, F, 2015)	2.18
" The population analysis identified age as a covariate of V/F (young 305 L; elderly 426 L), with a 50% longer mean elimination half-life in the elderly."	( Pharmacokinetics of Tramadol and O-Desmethyltramadol Enantiomers Following Administration of Extended-Release Tablets to Elderly and Young Subjects. Bouchard, S; Fradette, C; Mouksassi, MS; Skinner-Robertson, S; Varin, F, 2015)	0.74
" There was not a significant difference in the elimination half-life between age groups (1."	( Effects of age on the pharmacokinetics of tramadol and its active metabolite, O-desmethyltramadol following intravenous administration to foals. Knych, HK; McKemie, DS; Steffey, EP; White, AM, 2016)	0.7
"Combined analyses from 2 open-label, phase-1 studies-the pharmacokinetic profile of tramadol and its metabolite (M1) following a single oral dose of tramadol extended release (ER) (25 to 100 mg) in children (7 to 11 years old; study 1: n = 37) and adolescents (12 to 17 years old; study 2: n = 38) with painful conditions-were historically compared with that of healthy adults following similar dosing."	( Single-Dose Pharmacokinetic Study of Tramadol Extended-Release Tablets in Children and Adolescents. Richards, H; Van Peer, A; Vandenbossche, J, 2016)	0.93
"In these combined analyzes from 3 open-label, phase-1 studies, the pharmacokinetic profile of tramadol and its metabolite (M1) following administration of tramadol immediate-release (IR) tablets in children and adolescents, 7-16 years old (studies 1 and 2: n = 38; study 3: n = 21) with painful conditions following single oral dose of tramadol IR (25-100 mg) (studies 1 and 2) or multiple oral doses of tramadol IR tablets every 6 hours for 3 days (study 3) were compared with that of healthy adults following similar treatment."	( Single- and multiple-dose pharmacokinetic studies of tramadol immediate-release tablets in children and adolescents. Richards, H; Solanki, B; Van Peer, A; Vandenbossche, J, )	0.6
" In the present study, a pharmacokinetic approach was applied using two groups of five male Wistar rats administered a 20mg/kg dose of tramadol via intravenous (i."	( Evaluation of the route dependency of the pharmacokinetics and neuro-pharmacokinetics of tramadol and its main metabolites in rats. Gholami, M; Lavasani, H; Rouini, M; Sheikholeslami, B, 2016)	0.86
" The values of predicted pharmacokinetic parameters like Cmax (maximum blood drug level), Tmax (time required to attain maximum blood drug level), and AUC (area under blood drug concentration curve) ranged between 80."	( PREDICTIVE PHARMACOKINETICS OF TRAMADOL HYDROCHLORIDE FLOATING TABLETS. Guo, Z; Li, Z; Ma, X; Tao, Q; Wang, J; Wang, Y; Zhang, Y; Zhou, W, )	0.42
" The pharmacokinetic and elimination pattern of tramadol and its major phase I metabolites following oral or intramuscular administration in zebrafish tissues was achieved using electrospray ionization‑quadrupole‑time of flight/mass spectrometry (ESI‑Q‑TOF/MS) and gas chromatography/mass spectrometry (GC‑MS)."	( Distribution, pharmacokinetics and primary metabolism model of tramadol in zebrafish. Huang, H; Jin, H; Peng, H; Zhuo, H, 2016)	0.93
" Plasma concentrations of tramadol rapidly decreased in the first 2 hours for both doses with an elimination half-life of more than 40 minutes."	( Cardiovascular effects and intraoperative pharmacokinetics of tramadol in sheep undergoing spinal surgery. Bellini, L; De Benedictis, GM; De Vito, V; Della Rocca, G; Depase, A; Giorgi, M, 2017)	1
" The pharmacokinetic variables may be used to plan the dosage regime during general anaesthesia."	( Cardiovascular effects and intraoperative pharmacokinetics of tramadol in sheep undergoing spinal surgery. Bellini, L; De Benedictis, GM; De Vito, V; Della Rocca, G; Depase, A; Giorgi, M, 2017)	0.7
"This work proposes an application of a minimal complexity physiologically based pharmacokinetic model to predict tramadol concentration vs time profiles in horses."	( A physiologically based model for tramadol pharmacokinetics in horses. Abbiati, RA; Cagnardi, P; Manca, D; Ravasio, G; Villa, R, 2017)	0.94
"We compared the pharmacokinetic (PK) profiles of co-crystal of tramadol-celecoxib (CTC) vs."	( Pharmacokinetics of multiple doses of co-crystal of tramadol-celecoxib: findings from a four-way randomized open-label phase I clinical trial. Encina, G; Escriche, M; Gascón, N; Lahjou, M; Plata-Salamán, C; Sans, A; Sicard, E; Soler, L; Sust, M; Vaqué, A; Videla, S, 2018)	0.97
"The accuracy of physiologically based pharmacokinetic (PBPK) model prediction in children, especially those younger than 2 years old, has not been systematically evaluated."	( Predictive Performance of Physiologically Based Pharmacokinetic (PBPK) Modeling of Drugs Extensively Metabolized by Major Cytochrome P450s in Children. Al-Huniti, N; Bui, KH; Cheung, SYA; Johnson, TN; Li, J; Xu, H; Zhou, D; Zhou, W, 2018)	0.48
"1) At the dose administered, high plasma concentrations of tramadol and M1 were obtained, with half-life depending on the administration route."	( Preliminary pharmacokinetics of tramadol hydrochloride after administration via different routes in male and female B6 mice. Arras, M; Avenel, F; Bergadano, A; Draganov, DI; Evangelista Vaz, R; Rapp, C; Steiner, G, 2018)	1.01
"Four randomized, double-blind, placebo-controlled, 4-period drug-drug interaction studies were conducted in healthy subjects to evaluate the pharmacokinetic and pharmacodynamic (PD) interactions between mirogabalin and commonly used central nervous system depressants."	( Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Mirogabalin When Coadministered With Lorazepam, Zolpidem, Tramadol, or Ethanol: Results From Drug-Drug Interaction Studies in Healthy Subjects. Currie, A; Dishy, V; Dow, J; He, L; Ishizuka, H; Jansen, M; Mendell, J; Merante, D; Zahir, H, 2018)	0.69
" Tramadol's pharmacokinetic exposure was comparable between cohorts after adjusting for body weight; the pharmacokinetic exposure of O-desmethyltramadol and celecoxib was increased in Japanese subjects."	( Pharmacokinetics of Tramadol and Celecoxib in Japanese and Caucasian Subjects Following Administration of Co-Crystal of Tramadol-Celecoxib (CTC): A Randomised, Open-Label Study. Bennett, C; Dooner, H; Encabo, M; Encina, G; Escriche, M; Lorch, U; Mersmann, S; Mundin, G; Smith, K, 2019)	1.75
"Combination therapy of pregabalin and tramadol is used to treat chronic neuropathic pain; however, the pharmacokinetic (PK) interactions of these drugs has not been studied."	( A pharmacokinetic drug-drug interaction study between pregabalin and tramadol in healthy volunteers. Cho, JY; Chung, JY; Im, G; Kim, Y; Lee, JJS; Lee, S; Yoon, S, 2018)	0.99
" An increase in the elimination half-life and reduced clearance rate of tramadol were seen in the acetaminophen and ethanol groups, in comparison to the control group."	( Pharmacokinetic changes of tramadol in rats with hepatotoxicity induced by ethanol and acetaminophen in perfused rat liver model. Ardakani, YH; Esmaeili, Z; Ghazi-Khansari, M; Hassanzadeh, G; Lavasani, H; Mohammadi, S; Nezami, A; Rouini, MR, 2019)	1.04
" Interestingly, the PBPK model with the shortest CYP2D6 maturation half-life (PK-Sim) agreed best with the in vivo CYP2D6 maturation model."	( PBPK and its Virtual Populations: the Impact of Physiology on Pediatric Pharmacokinetic Predictions of Tramadol. T'jollyn, H; Van Bocxlaer, J; Vermeulen, A, 2018)	0.7
" Pharmacokinetic parameters were calculated using a one-compartment model with first-order input."	( Pharmacokinetics of orally administered tramadol in Muscovy ducks (Cairina moschata domestica). Allender, MC; Bailey, RS; Chinnadurai, SK; Papich, MG; Sheldon, JD, 2019)	0.78
" Cmax of tramadol for most CP patients was within the therapeutic range associated with its analgesic activity."	( Ketoprofen and tramadol pharmacokinetics in patients with chronic pancreatitis. Adrych, K; Grabowski, T; Grześkowiak, E; Karbownik, A; Mziray, M; Porażka, J; Siepsiak-Połom, M; Szałek, E, 2019)	1.28
" Recently, a number of studies have explored the associations of the CYP2D6*10 C188T polymorphism with pharmacokinetic and clinical outcomes of tramadol."	( The Associations Between CYP2D6*10 C188T Polymorphism and Pharmacokinetics and Clinical Outcomes of Tramadol: A Systematic Review and Meta-analysis. Cai, WK; He, GH; Lin, XQ; Wen, QH; Zhang, Z, 2020)	0.97
" In addition, we also found that CYP2D6*10 C188T had effects on the pharmacokinetic parameters of the metabolite of tramadol, O-desmethyltramadol, by sensitive analysis."	( The Associations Between CYP2D6*10 C188T Polymorphism and Pharmacokinetics and Clinical Outcomes of Tramadol: A Systematic Review and Meta-analysis. Cai, WK; He, GH; Lin, XQ; Wen, QH; Zhang, Z, 2020)	0.98
" Methods A pharmacokinetic and metabolic study was developed in cases of tramadol poisoned (n=96)."	( Assessment of tramadol pharmacokinetics in correlation with CYP2D6 and clinical symptoms. Ahmadimanesh, M; Ghazi-Khansari, M; Naeini, MB; Rouini, MR; Shadnia, S, 2020)	1.15
" However, the pharmacokinetic parameter calculation corrected by dose analysis identified no proportional increase with dose for the AUC of tramadol (T2: 2,663 ± 1,827 vs."	( Pharmacokinetic properties of tramadol and M1 metabolite in Northeast Brazilian donkeys (Equus asinus). Alves, LP; Araujo-Silva, G; de Macêdo, LB; de Oliveira Lima, I; de Oliveira, MGC; de Paula, VV; Mouta, AN; Pérez-Urizar, J, 2021)	1.11
"The objective of this study was to establish physiologically based pharmacokinetic (PBPK) models of tramadol and its active metabolite O-desmethyltramadol (M1) and to explore the influence of CYP2D6 gene polymorphism on the pharmacokinetics of tramadol and M1."	( Physiologically based pharmacokinetic modeling of tramadol to inform dose adjustment and drug-drug interactions according to CYP2D6 phenotypes. Jiang, X; Wang, L; Xu, M; Xu, W; Zeng, J; Zheng, L, 2021)	1.09
" This study describes the pharmacokinetic profile of tramadol when a single subcutaneous bolus of 2 mg/kg was initially administered to two koalas."	( Pharmacokinetic profile of injectable tramadol in the koala (Phascolarctos cinereus) and prediction of its analgesic efficacy. Govendir, M; Kimble, B; Valtchev, P; Vogelnest, L, 2021)	1.14
" Both primary and secondary pharmacokinetic parameters were similar."	( Evaluation of tramadol human pharmacokinetics and safety after co-administration of magnesium ions in randomized, single- and multiple-dose studies. Bujalska-Zadrożny, M; Buś-Kwaśnik, K; Filist, M; Gilant, E; Jarus-Dziedzic, K; Leś, A; Nagraba, Ł; Rudzki, PJ; Sasinowska-Motyl, M, 2021)	0.98
" A physiologically based pharmacokinetic model for tramadol and O-desmethyltramadol was developed and verified in PK-Sim version 8 and linked to respective models of quinidine and metoprolol to evaluate the impact of allosteric and competitive CYP2D6 inhibition on tramadol and O-desmethyltramadol exposure."	( Physiologically Based Pharmacokinetic Modeling to Assess the Impact of CYP2D6-Mediated Drug-Drug Interactions on Tramadol and O-Desmethyltramadol Exposures via Allosteric and Competitive Inhibition. Cicali, B; Cristofoletti, R; Dow, P; Long, T; Michaud, V; Schmidt, S; Turgeon, J, 2022)	1.18
"5 mg/kg to treat severe pain in children but the assay for tramadol in plasma samples for pharmacokinetic and toxicology studies does not often consider concurrently administered medications."	( HPLC-UV assay of tramadol and O-desmethyltramadol in human plasma containing other drugs potentially co-administered to participants in a paediatric population pharmacokinetic study. Hua, AJ; Lim, LY; Nguyen, MN; Salman, S; Tang, EKY; von Ungern Sternberg, BS; Yoo, O, 2021)	1.2

Excerpt	Reference	Relevance
" The case report questions the long term use of pain killers combined with psycho-active drugs in chronic non malignant pain, especially if pain is under control."	( Nightmares and hallucinations after long-term intake of tramadol combined with antidepressants. De Laat, M; Devulder, J; Dumoulin, K; Renson, A; Rolly, G, 1996)	0.54
"A sensitive and automated method for the separation and individual determination of tramadol enantiomers in plasma has been developed using solid-phase extraction (SPE) on disposable extraction cartridges (DECs) in combination with chiral liquid chromatography (LC)."	( Automated determination of tramadol enantiomers in human plasma using solid-phase extraction in combination with chiral liquid chromatography. Ceccato, A; Chiap, P; Crommen, J; Hubert, P, 1997)	0.82
" Few data are available concerning dose requirements of epidural ROPI when combined with morphine."	( A comparison of 0.1% and 0.2% ropivacaine and bupivacaine combined with morphine for postoperative patient-controlled epidural analgesia after major abdominal surgery. Joris, JL; Lahaye-Goffart, B; Lamy, ML; Ledoux, D; Senard, M; Toussaint, PJ, 2002)	0.31
"Dexmedetomidine in combination with morphine PCA provided better analgesia for ESWL and was associated with higher patients' and urologist's satisfaction when compared with a tramadol/midazolam PCA combination."	( Dexmedetomidine in combination with morphine PCA provides superior analgesia for shockwave lithotripsy. Alhashemi, JA; Kaki, AM, 2004)	0.52
"Our objective was to investigate the frequency of potential drug-drug interactions between the prodrugs losartan, codeine, and tramadol and drugs known to inhibit their activation in hospitalized patients."	( Drug interactions with the potential to prevent prodrug activation as a common source of irrational prescribing in hospital inpatients. Laine, K; Tirkkonen, T, 2004)	0.53
"Liquid phase microextraction by back extraction (LPME-BE) combined with high performance liquid chromatography (HPLC)-fluorescence detection was developed for the determination of tramadol in human plasma."	( Determination of tramadol in human plasma and urine samples using liquid phase microextraction with back extraction combined with high performance liquid chromatography. Ebrahimzadeh, H; Rouini, MR; Sedighi, A; Yamini, Y, 2008)	0.88
"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)	0.81
"The aim of this work was to investigate the effect on antioxidant potential of some commonly used drugs (morphine, tramadol, bromocriptine, haloperidol and azithromycin) on immobilization stress (IS) combined with cold restraint stress (CRS) in the rat."	( Antioxidant effects of some drugs on immobilization stress combined with cold restraint stress. Janicijevic-Hudomal, S; Kaurinovic, B; Popovic, M; Rasic, J; Trivic, S; Vojnović, M, 2009)	0.56
"This double blind, randomized, controlled trial investigated whether a single preoperative intravenous (iv) dose of tramadol (100 mg) given 30 min before abdominal hysterectomy resulted in improved analgesic efficacy, reduced postoperative morphine patient-controlled analgesia (PCA) use and reduced side effects when combined with a postoperative small-dose tramadol infusion."	( Preoperative tramadol combined with postoperative small-dose tramadol infusion after total abdominal hysterectomy: a double-blind, randomized, controlled trial. Liu, Y; Shen, X; Wang, F; Xu, S, )	0.71
"A simple, rapid and sensitive analytical method for preconcentration and determination of tramadol in different biological samples have been developed using solvent bar microextraction (SBME) combined with gas chromatography-mass spectrometry (GC-MS)."	( Optimization of solvent bar microextraction combined with gas chromatography mass spectrometry for preconcentration and determination of tramadol in biological samples. Ghasemi, E, 2012)	0.8
"To evaluate the effectiveness and safety of epidural lidocaine in combination with either tramadol or neostigmine for perineal analgesia in horses."	( Efficacy of epidural lidocaine combined with tramadol or neostigmine on perineal analgesia in the horse. DeRossi, R; Maciel, FB; Módolo, TJ; Pagliosa, RC, 2013)	0.87
"To compare the effects of tramadol alone, or in combination with dipyrone or meloxicam, on postoperative pain and analgesia requirement after unilateral mastectomy with or without ovariohysterectomy in dogs."	( Effects of tramadol alone, in combination with meloxicam or dipyrone, on postoperative pain and the analgesic requirement in dogs undergoing unilateral mastectomy with or without ovariohysterectomy. Bressan, TF; Campagnol, D; Coelho, K; Monteiro, BS; Monteiro, ER; Teixeira, RC, 2013)	1.08
" Before the end of surgery, dogs were randomly assigned to receive intravenous tramadol alone (3 mg kg(-1), group T), combined with dipyrone (30 mg kg(-1), group TD) or meloxicam (0."	( Effects of tramadol alone, in combination with meloxicam or dipyrone, on postoperative pain and the analgesic requirement in dogs undergoing unilateral mastectomy with or without ovariohysterectomy. Bressan, TF; Campagnol, D; Coelho, K; Monteiro, BS; Monteiro, ER; Teixeira, RC, 2013)	1.01
"Under the conditions of this study, tramadol alone or in combination with dypyrone or meloxicam provided effective analgesia for 24 hours in most dogs after unilateral mastectomy with or without ovariohysterectomy."	( Effects of tramadol alone, in combination with meloxicam or dipyrone, on postoperative pain and the analgesic requirement in dogs undergoing unilateral mastectomy with or without ovariohysterectomy. Bressan, TF; Campagnol, D; Coelho, K; Monteiro, BS; Monteiro, ER; Teixeira, RC, 2013)	1.05
"To investigate the clinical efficacy of X-ray imaging combined with skin stimulation potential-guided percutaneous radiofrequency thermocoagulation of the Gasserian ganglion for treatment of primary trigeminal neuralgia."	( A prospective study of X-ray imaging combined with skin stimulation potential-guided percutaneous radiofrequency thermocoagulation of the Gasserian ganglion for treatment of trigeminal neuralgia. Chen, J; Chen, Y; Nie, F; Qin, W; Shi, Y; Su, D; Wang, H; Wang, S, 2014)	0.4
" In the study group, the patients underwent X-ray imaging combined with skin stimulation potential-guided percutaneous radiofrequency thermocoagulation of the Gasserian ganglion."	( A prospective study of X-ray imaging combined with skin stimulation potential-guided percutaneous radiofrequency thermocoagulation of the Gasserian ganglion for treatment of trigeminal neuralgia. Chen, J; Chen, Y; Nie, F; Qin, W; Shi, Y; Su, D; Wang, H; Wang, S, 2014)	0.4
" All individual drugs and dexmedetomidine combination with either tramadol or amitriptyline were effective in reducing mechanical allodynia and hyperalgesia."	( The effects of dexmedetomidine alone and in combination with tramadol or amitriptyline in a neuropathic pain model. Abd-Ellatief, RB; Farghaly, HS; Khedr, EM; Kotb, HI; Moftah, MZ; Mostafa, MG, )	0.61
"To investigate the extent to which clinicians avoid well-established drug-drug interactions associated with warfarin."	( Adherence to guidelines for avoiding drug interactions associated with warfarin--a Nationwide Swedish Register Study. Andersson, ML; Lindh, JD; Mannheimer, B, 2014)	0.4
" Alfaxalone, alone or in combination with tramadol, did not produce satisfactory results for use as an anaesthetic for this species."	( Anaesthetic effects in the ferret of alfaxalone alone and in combination with medetomidine or tramadol: a pilot study. García-Olmo, DC; Giral, M; Gómez de Segura, IA; Gómez-Juárez, M, 2014)	0.89
"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)	0.81
"We present a database of prescription drugs and international normalized ratio (INR) data and the applied methodology for its use to assess drug-drug interactions with vitamin K antagonists (VKAs)."	( Pharmacoepidemiological assessment of drug interactions with vitamin K antagonists. dePont Christensen, R; Gagne, JJ; Hallas, J; Larsen, TB; Pottegård, A; Wang, SV, 2014)	0.4
"Seventy-four patients undergoing TURBT were randomly allocated to receive either glycopyrrolate 10 μg/kg (glycopyrrolate group, n = 37) or atropine 15 μg/kg (atropine group, n = 37) in combination with neostigmine 25 μg/kg at the end of surgery for reversal of neuromuscular blockade."	( Effect of glycopyrrolate versus atropine coadministered with neostigmine for reversal of rocuronium on postoperative catheter-related bladder discomfort in patients undergoing transurethral resection of bladder tumor: a prospective randomized study. Kim, HC; Lim, SM; Park, HP; Seo, H, 2015)	0.42
"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)	0.86
" 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)	0.65
"This study was aimed to evaluate the efficacy of preemptive analgesia (PA) by using celecoxib combined with low-dose tramadol/acetaminophen (tramadol/APAP) in treating post-operative pain of patients undergoing unilateral total knee arthroplasty (TKA)."	( Preemptive analgesia by using celecoxib combined with tramadol/APAP alleviates post-operative pain of patients undergoing total knee arthroplasty. Luo, J; Xu, Z; Zhang, H; Zhang, J; Zhou, A, 2017)	0.91
" The magnitude of drug-drug interaction between dextromethorphan and paroxetine was higher in homozygous than in heterozygous subjects (14."	( Impact of CYP2D6 Functional Allelic Variations on Phenoconversion and Drug-Drug Interactions. Daali, Y; Desmeules, J; Lenglet, S; Matthey, A; Storelli, F; Thomas, A, 2018)	0.48
"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
"Four randomized, double-blind, placebo-controlled, 4-period drug-drug interaction studies were conducted in healthy subjects to evaluate the pharmacokinetic and pharmacodynamic (PD) interactions between mirogabalin and commonly used central nervous system depressants."	( Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Mirogabalin When Coadministered With Lorazepam, Zolpidem, Tramadol, or Ethanol: Results From Drug-Drug Interaction Studies in Healthy Subjects. Currie, A; Dishy, V; Dow, J; He, L; Ishizuka, H; Jansen, M; Mendell, J; Merante, D; Zahir, H, 2018)	0.69
" There are several randomized controlled trials (RCTs) of dexmedetomidine (DEX) combined with tramadol for PCIA in Chinese surgical patients."	( Efficacy and safety of dexmedetomidine combined with tramadol for patient-controlled intravenous analgesia in Chinese surgical patients: A systematic review and meta-analysis. Chen, F; Chen, P; Lei, J; Zhou, B, 2020)	1.03
"The RCTs of DEX combined with tramadol for PCIA were gathered from the PubMed, Excerpta Medica Database, Cochrane Library, Cochrane Library, China National Knowledge Infrastructure database, and VIP databases."	( Efficacy and safety of dexmedetomidine combined with tramadol for patient-controlled intravenous analgesia in Chinese surgical patients: A systematic review and meta-analysis. Chen, F; Chen, P; Lei, J; Zhou, B, 2020)	1.1
"To investigate the effect of local usage of prilocaine and ıts combination with tramadol on the pain and anxiety levels of patients during nasal packing removal."	( Effect of prilocaine and its combination with tramadol on anxiety and pain during nasal packing removal. Arslan, E; Tulaci, KG; Tulaci, RG; Yazici, H, 2020)	1.04
" Patients whose Merocel nasal packings infiltrated with prilocaine (P group), prilocaine combined with tramadol 1 mg/kg (P + T1 group), prilocaine combined with tramadol 2 mg/kg (P + T2 group), or normal saline solution (Control group) before nasal packing removal were compared for their pain, sedation, and anxiety related to this removal procedure."	( Effect of prilocaine and its combination with tramadol on anxiety and pain during nasal packing removal. Arslan, E; Tulaci, KG; Tulaci, RG; Yazici, H, 2020)	1.03
"This study aimed to explore the effect of patient-controlled intravenous analgesia (PCIA) using tramadol combined with butorphanol on uterine cramping pain in women undergoing repeat caesarean section."	( The analgesic effect of tramadol combined with butorphanol on uterine cramping pain after repeat caesarean section: a randomized, controlled, double-blind study. Cai, L; Cai, Q; Chen, W; Fan, M; Gong, H, 2020)	1.08
" PCIA using tramadol combined with butorphanol or sufentanil was randomly performed for postoperative pain control."	( The analgesic effect of tramadol combined with butorphanol on uterine cramping pain after repeat caesarean section: a randomized, controlled, double-blind study. Cai, L; Cai, Q; Chen, W; Fan, M; Gong, H, 2020)	1.24
"PCIA using tramadol combined with butorphanol provided a better analgesic effect and accelerated postoperative rehabilitation compared with sufentanil, and may be an optimal analgesic strategy for women undergoing repeat caesarean section."	( The analgesic effect of tramadol combined with butorphanol on uterine cramping pain after repeat caesarean section: a randomized, controlled, double-blind study. Cai, L; Cai, Q; Chen, W; Fan, M; Gong, H, 2020)	1.25
" Furthermore, we used PBPK modeling to prospectively predict the extent of drug-drug interactions (DDIs) in the presence of genetic polymorphisms when tramadol was co-administered with the CYP2D6 inhibitors duloxetine and paroxetine."	( Physiologically based pharmacokinetic modeling of tramadol to inform dose adjustment and drug-drug interactions according to CYP2D6 phenotypes. Jiang, X; Wang, L; Xu, M; Xu, W; Zeng, J; Zheng, L, 2021)	1.07
" We discuss the case of a hospitalized patient in the United States diagnosed with COVID-19 pneumonia who developed acute pain crisis secondary to a drug-drug interaction between tramadol and remdesivir, and we propose a possible mechanism of interaction."	( Acute Pain Crisis Caused by Tramadol Remdesivir Drug-Drug Interaction. Feely, M; Ho, I; Miller, G; Teoli, D; Thompson, V; Vlaminck, B; Wright, J, 2021)	1.11
" This study aimed to compare the analgesic effects of tramadol alone and combined with butorphanol or flurbiprofen axetil after a cesarean section."	( Analgesic outcomes of tramadol alone and in combination with Butorphanol or Flurbiprofen Axetil after cesarean section: a retrospective study with propensity score matching analysis. Bao, X; Deng, Q; Li, H; Liang, Y; Liu, W; Peng, J; Tan, D; Wu, Z; Yan, G; Yang, G, 2022)	1.28
" To evaluate the efficacy and safety of adding morphine to periarticular infiltration analgesia (PIA) combined with single-dose epidural morphine for the patients undergoing TKA."	( Effects of Adding Morphine to Periarticular Infiltration Analgesia Combined with Single Dose Epidural Morphine in Total Knee Arthroplasty: A Randomized Controlled Study. Cao, L; Gu, W; Guo, X; Li, Y; Wulamu, W; Yushan, N; Zhang, X, 2023)	0.91
"PIA combined with single-dose epidural morphine effectively reduces early postoperative pain and tramadol requirement as well as few complications, which can become a safe and effective measure to improve postoperative pain after TKA."	( Effects of Adding Morphine to Periarticular Infiltration Analgesia Combined with Single Dose Epidural Morphine in Total Knee Arthroplasty: A Randomized Controlled Study. Cao, L; Gu, W; Guo, X; Li, Y; Wulamu, W; Yushan, N; Zhang, X, 2023)	1.13
" Therefore, the current study investigated the immune effects induced in healthy mice by repeated administration of tramadol alone or in combination with acetaminophen or dexketoprofen."	( Immunomodulation by tramadol combined with acetaminophen or dexketoprofen: In vivo animal study. Bryniarski, K; Cieślik, M; Fedor, A; Filipczak-Bryniarska, I; Gębicka, M; Kozlowski, M; Kruk, G; Nazimek, K; Nowak, B; Pełka-Zakielarz, J; Skalska, P, 2023)	1.44

Excerpt	Reference	Relevance
"The absolute bioavailability of tramadol hydrochloride (rac-1(e)-(m-methoxyphenyl)-2-(e)-(dimethylaminomethyl)cyclohexan- 1(a)-ol hydrochloride, CG 315) after the oral administration of Tramal capsules was determined in a balanced cross-over study in 10 male volunteers."	( Bioavailability of enteral tramadol formulations. 1st communication: capsules. Barth, H; Lintz, W; Osterloh, G; Schmidt-Böthelt, E, 1986)	0.85
"The pharmacokinetics and the absolute bioavailability of tramadol hydrochloride (CAS 36282-47-0) after oral administration of Tramal drops (with ethanol) were determined in a balanced cross-over study in 8 (4 male and 4 female) volunteers in comparison with the intravenous injection."	( Pharmacokinetics of tramadol and bioavailability of enteral tramadol formulations. 2nd communication: drops with ethanol. Barth, H; Becker, R; Frankus, E; Lintz, W; Schmidt-Böthelt, E, 1998)	0.87
"The pharmacokinetics and the absolute bioavailability of tramadol hydrochloride (CAS 36282-47-0) after rectal administration of tramadol suppositories (Tramal) were determined in a balanced crossover study in 10 female volunteers in comparison with the intravenous injection."	( Pharmacokinetics of tramadol and bioavailability of enteral tramadol formulations. 3rd Communication: suppositories. Barth, H; Lintz, W; Osterloh, G; Schmidt-Böthelt, E, 1998)	0.87
" The investigation also showed an only slightly diminished bioavailability of the tramadol sustained release capsules compared to the instant release formulation."	( Pharmacokinetic properties of tramadol sustained release capsules. 2nd communication: investigation of relative bioavailability and food interaction. Bias-Imhoff, U; Momberger, H; Raber, M; Schulz, HU; Schürer, M, 1999)	0.82
" As a result of the statistical analysis of AUCss(48-72 h) after logarithmic transformation a bioavailability of 100% for the sustained release capsules compared with the instant release capsules was obtained."	( Pharmacokinetic properties of tramadol sustained release capsules. 3rd communication: investigation of relative bioavailability under steady state conditions. Krupp, S; Momberger, H; Raber, M; Schulz, HU; Schürer, M, 1999)	0.59
" The bioavailability of a new tramadol hydrochloride injection (Limadol) was compared with a commercially available reference product by intramuscular administration in twelve healthy Chinese male volunteers by a standard two-way cross-over trial."	( Bioequivalence study of tramadol by intramuscular administration in healthy volunteers. Chao, CK; Chen, CM; Liu, CM; Su, LL; Yang, TH; Yu, LL, 2000)	0.9
"The aim of this study was to investigate the bioavailability of tramadol hydrochloride after oral administration of Tramadol--50 mg capsules, made in Synteza Pharmaceutical-Chemical Company in Poznań."	( Bioavailability of tramadol hydrochloride from tramadol--capsules 50 mg. Drobnik, L; Dyderski, S; Szkutnik, D; Zgrabczyńska, M, )	0.7
"the bioavailability of tramadol hydrochloride after administration of Tramadol is the same as after administration of Tramal, whose clinical efficacy was tested before."	( Bioavailability of tramadol hydrochloride from tramadol--capsules 50 mg. Drobnik, L; Dyderski, S; Szkutnik, D; Zgrabczyńska, M, )	0.77
" Following oral administration the bioavailability of tramadol is high (70-90%) and with new slow release preparations twice daily administration enables effective pain control."	( Tramadol--the impact of its pharmacokinetic and pharmacodynamic properties on the clinical management of pain. Klotz, U, 2003)	2.01
"9 hours and have a bioavailability of 87-95% compared with capsules."	( Clinical pharmacology of tramadol. Grond, S; Sablotzki, A, 2004)	0.63
" However, it should be noted that there is a difference in the bioavailability between the 2 formulations of up to 30%, which may explain the findings."	( The analgesic efficacy of intravenous versus oral tramadol for preventing postoperative pain after third molar surgery. Lirk, P; Ong, CK; Sow, BW; Tan, JM, 2005)	0.58
" Data of kinetics show a very high oral bioavailability and the sustained-release (SR) formulations assure a 24-h coverage through the constant blood levels."	( Tramadol. Focus on musculoskeletal and neuropathic pain. Coluzzi, F; Mattia, C, 2005)	1.77
" Tramadol SR capsules had identical bioavailability to tramadol immediate-release (IR) capsules with lower peak concentrations and less fluctuation in plasma concentrations."	( Tramadol sustained-release capsules. Keating, GM, 2006)	2.69
" There were no statistical differences between the absolute bioavailability of tramadol in EMs and PMs."	( Enantioselective pharmacokinetics of tramadol in CYP2D6 extensive and poor metabolizers. Brøsen, K; Damkier, P; Pedersen, RS, 2006)	0.83
" Following oral administration the bioavailability of tramadol is high and with new slow release preparations twice daily administration enables effective pain control."	( [An atypical opioid analgesic: tramadol]. Aydinli, I; Keskinbora, K, 2006)	0.87
"The aim of this study was to compare the pharmacokinetic profile and oral bioavailability of Tramadol Contramid once-daily (o."	( Comparative bioavailability between two Tramadol once-daily oral formulations. Encina, G; Hernandez-Lopez, C; Karhu, D; Martinez-Farnos, L; Perez-Campos, T; Rovira, S, )	0.62
" Tramadol ER administered once daily is equivalent in bioavailability to immediate-release tramadol administered four times daily, with prolonged absorption and lower peak plasma concentrations."	( Tramadol extended-release tablets. Curran, MP; Hair, PI; Keam, SJ, 2006)	2.69
"41 L kg(-1), and the mean systemic bioavailability (F) was 101."	( The pharmacokinetics, metabolism and urinary detection time of tramadol in camels. Abdel Hadi, AA; Al Masri, J; Barezaik, IM; Elghazali, M; Eltayeb, FM; Wasfi, IA, 2008)	0.59
" The mean absorption time was 72+/-22 min and the bioavailability 111+/-39%."	( Pharmacokinetics of tramadol in horses after intravenous, intramuscular and oral administration. Britzi, M; Eytan, B; Lifschitz, T; Shilo, Y; Soback, S; Steinman, A, 2008)	0.67
"Objective of this study was to investigate the rate and extent of tramadol bioavailability following evening versus morning administration."	( [Importance of the formulation for a chronopharmacologically optimised way of pain therapy. Results of a comparative bioavailability study of tramadol extended-release capsules after single-dose evening versus morning administration]. Blume, H; Schug, B; Vanderbist, F; Warnke, A, 2008)	0.78
"Tramadol bioavailability showed a substantial increase in patients with primary liver cancer and secondary metastatic than that of control (98 percent, 75 percent, and 68 percent, respectively)."	( Pharmacokinetics of oral tramadol in patients with liver cancer. Abd El-Rahman, AM; Fares, KM; Fouad, IA; Kotb, HI; Mostafa, MG, )	1.88
" The plasma absolute bioavailability values of tramadol after intranasal and oral administration were 73."	( Pharmacokinetics of tramadol in rat plasma and cerebrospinal fluid after intranasal administration. Chai, X; Chen, Q; He, N; Pi, J; Tao, T; Wu, J; Zhao, Y, 2008)	0.93
" In vivo study was also performed on six healthy human volunteers and various pharmacokinetic parameters (cmax, tmax, AUC0-24, MRT) and relative bioavailability were calculated."	( Development and biopharmaceutical evaluation of extended release formulation of tramadol hydrochloride based on osmotic technology. Kumar, P; Mishra, B; Singh, S, 2009)	0.58
"The objective of this study was to investigate the rate and extent of tramadol bioavailability following evening versus morning intake of an extended-release pellet system designed for once daily administration."	( Significance of the biopharmaceutical properties of tramadol sustained-release formulations for chrono-pharmacologically optimized treatment of pain from various sources. Blume, H; Schug, B; Vanderbist, F; Warnke, A, 2009)	0.84
" The absolute bioavailability of tramadol via rectal administration was 10 (SD 4)%."	( Pharmacokinetics of tramadol and its major metabolites following rectal and intravenous administration in dogs. Del Carlo, S; Giorgi, M; Kowalski, CJ; Saccomanni, G; Łebkowska-Wieruszewska, B, 2009)	0.96
" In addition, the oral bioavailability was 97."	( Pharmacokinetics of intravenous and oral tramadol in the bald eagle (Haliaeetus leucocephalus). Cox, SK; Jones, MP; Martin-Jimenez, T; Souza, MJ, 2009)	0.62
" The bioavailability of the drug, ranging between 84-102% (mean 92%), was within the generally accepted values for a positive bioequivalence decision of (80-125%)."	( Pharmacokinetics of tramadol and metabolites after injective administrations in dogs. Del Carlo, S; Giorgi, M; Kowalski, CJ; Saccomanni, G; Łebkowska-Wieruszewska, B, 2010)	0.68
" Because of the poor bioavailability and adverse effects noted in this study, the oral administration of tramadol in alpacas cannot be recommended without further research."	( Pharmacokinetics of tramadol and its major metabolites in alpacas following intravenous and oral administration. Boothe, DM; Duran, SH; Edmondson, MA; Ravis, WR; Stewart, AJ, 2012)	0.92
" An intravenous injection group to determine the pharmacokinetic parameters for estimation of the transdermal absorption rate in guinea pigs was also included."	( In-vitro and in-vivo transdermal iontophoretic delivery of tramadol, a centrally acting analgesic. Ito, M; Kinoshita, M; Kominami, K; Mafune, S; Sutoh, C; Takasuga, S; Yamamoto, R; Yoshida, Y, 2011)	0.61
" In the in-vivo pharmacokinetic study, plasma concentrations of tramadol steadily increased and reached steady state (336 ng/ml) 3 h after initiation of current supply, and the in-vivo steady-state transdermal absorption rate was 499 µg/cm(2) per h as calculated by a constrained numeric deconvolution method."	( In-vitro and in-vivo transdermal iontophoretic delivery of tramadol, a centrally acting analgesic. Ito, M; Kinoshita, M; Kominami, K; Mafune, S; Sutoh, C; Takasuga, S; Yamamoto, R; Yoshida, Y, 2011)	0.85
" Bioavailability of oral tramadol was reduced by rifampicin from 66 to 49 % (P = 0."	( Rifampicin markedly decreases the exposure to oral and intravenous tramadol. Hagelberg, NM; Laine, K; Neuvonen, M; Neuvonen, PJ; Olkkola, KT; Saari, TI; Saarikoski, T; Scheinin, M, 2013)	0.93
"In view of the changes in the pharmacokinetics of paracetamol and tramadol in the patients after gastric resection for both formulations compared the conventional tablet seems to be more appropriate due to the comparable rate of absorption of both substances, higher concentrations of tramadol and comparable exposure to paracetamol."	( The pharmacokinetics of the effervescent vs. conventional tramadol/paracetamol fixed-dose combination tablet in patients after total gastric resection. Burchardt, P; Cieśla, S; Grabowski, T; Grześkowiak, E; Karbownik, A; Kokot, ZJ; Murawa, D; Murawa, P; Połom, K; Szałek, E; Urbaniak, B; Więckiewicz, A; Wolc, A, 2014)	0.88
" Data used for the analysis were pooled from two phase I bioavailability studies with immediate (IR) and prolonged release (PR) formulations in healthy volunteers."	( Population pharmacokinetic modelling of tramadol using inverse Gaussian function for the assessment of drug absorption from prolonged and immediate release formulations. Brvar, N; Grabnar, I; Mateović-Rojnik, T, 2014)	0.67
" This study compared the bioavailability of tramadol after different administration routes in rats (oral, buccal and nasal)."	( Bioavailability of tramadol hydrochloride after administration via different routes in rats. Wang, X; Zhang, H; Zhang, Q; Zhao, Y, 2014)	0.99
" Bioavailability of tramadol was poor [3."	( Pharmacokinetics of tramadol following intravenous and oral administration in male rhesus macaques (Macaca mulatta). Christe, KL; Kelly, KR; Pypendop, BH, 2015)	1.06
" A one-compartment population model of total tramadol concentration was parameterized with clearance (CL/F), volume of distribution (V/F), and mixed order absorption (first-order and zero-order absorption rate constants with lag times)."	( Pharmacokinetics of Tramadol and O-Desmethyltramadol Enantiomers Following Administration of Extended-Release Tablets to Elderly and Young Subjects. Bouchard, S; Fradette, C; Mouksassi, MS; Skinner-Robertson, S; Varin, F, 2015)	1
" In-vivo absorption study showed a significant increase in bioavailability (7."	( In vitro and preclinical assessment of factorial design based nanoethosomes transgel formulation of an opioid analgesic. Ahmed, S; Ali, A; Aqil, M; Gull, A; Sarim Imam, S; Zafar, A, 2016)	0.43
" The purpose of this study was to determine if administration of oral tramadol with suspected metabolism inhibitors (ketoconazole, cimetidine) would lead to improved bioavailability of tramadol and M1."	( The effects of ketoconazole and cimetidine on the pharmacokinetics of oral tramadol in greyhound dogs. Black, J; KuKanich, B; KuKanich, K, 2017)	0.92
"When tramadol administered intraperitoneally, the absorption rate of this drug was reduced, and a lower Cmax (40%) with longer Tmax (eight-fold) was achieved."	( Evaluation of the Ecstasy influence on tramadol and its main metabolite plasma concentration in rats. Hosseinzadeh Ardakani, Y; Jamali, B; Lavasani, H; Rouini, MR; Sheikholeslami, B, 2017)	1.24
" This randomised, open-label, crossover study compared the bioavailability of both components after CTC administration under fed and fasting conditions."	( The Effect of Food on Tramadol and Celecoxib Bioavailability Following Oral Administration of Co-Crystal of Tramadol-Celecoxib (CTC): A Randomised, Open-Label, Single-Dose, Crossover Study in Healthy Volunteers. Encabo, M; Encina, G; Escriche, M; Gascon, N; Lahjou, M; Plata-Salamán, C; Sicard, E; Smith, K; Videla, S, 2018)	0.8
"As reported for standard-formulation celecoxib, food increased the bioavailability of celecoxib from single-dose CTC."	( The Effect of Food on Tramadol and Celecoxib Bioavailability Following Oral Administration of Co-Crystal of Tramadol-Celecoxib (CTC): A Randomised, Open-Label, Single-Dose, Crossover Study in Healthy Volunteers. Encabo, M; Encina, G; Escriche, M; Gascon, N; Lahjou, M; Plata-Salamán, C; Sicard, E; Smith, K; Videla, S, 2018)	0.8
"Failure to recognize the impact of various situations described throughout this work, including the bioavailability due to loss of oral route, due to pharmacokinetics and pharmacodynamics of the various drugs, either in the context of the impaired metabolism or excretion, or in due to pharmacological interactions, conditions a serious risk of subtreatment of pain and consequent impact in terms of quality of life."	( [Opioids for Cancer Pain and its Use under Particular Conditions: A Narrative Review]. Brás, M; Fragoso, M; Vieira, C, 2019)	0.51
"The objective of this study was to develop a novel acetaminophen and tramadol hydrochloride-loaded soft capsule (ATSC) with enhanced bioavailability of tramadol."	( Acetaminophen and tramadol hydrochloride-loaded soft gelatin capsule: preparation, dissolution and pharmacokinetics in beagle dogs. Cho, JH; Choi, HG, 2021)	1.19
"Bioequivalence tests are fundamental step in assessing the equivalence in bioavailability between a test and reference product."	( Multivariate Assessment for Bioequivalence Based on the Correlation of Random Effect. An, H; Shin, D, 2021)	0.62
" 1-H-benzotriazole, carbamazepine, citalopram, lamotrigine, sucralose, tramadol, and venlafaxine (>80 % frequency of appearance in effluents) were assessed with respect to their bioavailability in soil as part of different scenarios of irrigation with reclaimed water following a qualitative approach."	( Multiclass target analysis of contaminants of emerging concern including transformation products, soil bioavailability assessment and retrospective screening as tools to evaluate risks associated with reclaimed water reuse. Beretsou, VG; Fatta-Kassinos, D; Lundy, L; Manoli, K; Michael, C; Nika, MC; Revitt, DM; Sui, Q; Thomaidis, NS, 2022)	0.95

Excerpt	Relevance	Reference
" The first dosage was 100 mg of all substances."	( [Use of tramadol versus pethidine versus denaverine suppositories in labor--a contribution to noninvasive therapy of labor pain]. Bredow, V, 1992)	0.72
" Subjective, behavioral and miotic changes were assessed prior to dosing and intermittently for 12 h after drug administration."	( Abuse potential and pharmacological comparison of tramadol and morphine. Jasinski, DR; Preston, KL; Testa, M, 1991)	0.53
"Tramadol at the dosage of 1 mg per kg body weight was given intravenously to 110 adult patients who developed postoperative shivering."	( The use of tramadol hydrochloride in the treatment of post-anesthetic shivering. Jirasirithum, S; Pausawasdi, S; Phanarai, C, 1990)	2.11
"This paper compares 2 dosage regimens using the new analgesic Tramadol for outpatient interval laparoscopic sterilization."	( The efficacy of tramadol in the interval laparoscopic sterilization: a comparison of two dosage regimen. Chaturachinda, K; Padmasuta, K; Pausawasdi, S; Tangtrakul, S, 1988)	0.86
" The severity and the duration of this intoxication are not explained solely by the high dosage of Tramadol."	( [Acute poisoning with a narcotic (Tramadol) in an infant of five weeks]. Beutler, A; Bianchetti, MG; Ferrier, PE, 1988)	0.77
" ED50 values were derived from the dose-response lines."	( Intrathecal injection of codeine, buprenorphine, tilidine, tramadol and nefopam depresses the tail-flick response in rats. Bernatzky, G; Jurna, I, 1986)	0.51
" The daily dosage was limited to 400 mg."	( Clinical investigation on the development of dependence during oral therapy with tramadol. Barth, H; Flohé, L; Giertz, H; Richter, W, 1985)	0.5
" With the dosage used in this experiment, there is no difference in the analgesic effect of tramadol and pethidine."	( [Characterization of the effect of analgesics on the assessment of experimental pain in man. Pethidine and tramadol in a double-blind comparison]. Madler, C; Morawetz, RF; Parth, P, 1984)	0.7
" Although a higher dosage of Tramadol reduces significantly the supplementary barbiturate dosage per kilogram bodyweight per minute which is required, it has no effect on the incidence of reflex movements, nor does it prevent the marked intraoperative rise of diastolic blood pressure."	( [The clinical usefulness of Tramadol-infusion anaesthesia (author's transl)]. Rothhammer, A; Skrobek, W; Weis, KH, 1981)	0.85
" To achieve an excellent pain relief by higher dosage of DHE and tramadol need further randomized investigation."	( [Influence of dihydroetorphine hydrochloride and tramadol on labor pain and umbilical blood gas]. Li, E; Weng, L, 1995)	0.78
" Remedication with the same drug at the same dosage was allowed if pain relief was unsatisfactory."	( Efficacy and safety of oral tramadol and pentazocine for postoperative pain following prolapsed intervertebral disc repair. Adriaensen, H; Callebaut, V; Camu, F; Coppejans, H; Debois, V; Kupers, R; Verborgh, C, 1995)	0.59
" The format provides a brief description of dosage and available dosage forms together with pharmaceutical aspects including preparation, administration and storage."	( Tramadol (zydol, Searle). MacConnachie, AM, 1995)	1.73
"Prosidol, a new Russian narcotic analgesic, was used in various dosage forms (buccal and oral tablets, injection solution) in 113 cancer patients for the treatment of chronic pain, as a component of total anesthesia, and for postoperative analgesia."	( [First experience in the use of a new Russian narcotic analgesic prosidol in oncology]. Beresnev, VA; Loseva, NA; Novikov, GA; Osipova, NA; Prokhorov, BM; Smolina, TA; Vetsheva, MS; Zemskaia, SIu, )	0.13
" Tramadol in 100 mg/2 ml vials and Nisidin in 2 ml vials were administered parenterally at a dosage of three vials a day during the first three days of the post-operative period."	( Post-operative analgesia with tramadol: a controlled study compared with an analgesic combination. Canepa, G; Cerruti, S; Di Somma, C; Ghia, M; Reali, M; Stasi, M; Trezzi, P; Vadalà, A, 1993)	1.48
" We conclude that a single dose of 150 mg tramadol given at the end of surgery provided postoperative analgesia equivalent to that provided by this dosage regimen of epidural morphine for the initial postoperative period."	( Intravenous tramadol versus epidural morphine for postthoracotomy pain relief: a placebo-controlled double-blind trial. Gordon, PC; Heijke, SA; James, MF, 1996)	0.94
" The recommended dosage is 50 to 100 mg every 4 to 6 hours; however, regular administration is an alternative, particularly for chronic pain states such as osteoarthritis, where the use of the recently developed sustained release formulation may represent an important advantage."	( Pharmacology and clinical experience with tramadol in osteoarthritis. Katz, WA, 1996)	0.56
" Repetitive dosing (1/4 of the greatest dose every 30 min) was as effective as a single bolus dose for both drugs."	( Attenuation of c-Fos expression in the rat lumbosacral spinal cord by morphine or tramadol following noxious colorectal distention. Gebhart, GF; Stitt, S; Traub, RJ, 1995)	0.52
" The tramadol dosage had recently been increased, resulting in what was believed to be serotonergic syndrome."	( Possible serotonin syndrome associated with tramadol and sertraline coadministration. Blackburn, KH; Mason, BJ, 1997)	1.07
"Serotonin syndrome is a toxic hyperserotonergic state that develops soon after initiation or dosage increments of the offending agent."	( Possible serotonin syndrome associated with tramadol and sertraline coadministration. Blackburn, KH; Mason, BJ, 1997)	0.56
"The pharmacology, pharmacokinetics, efficacy, adverse effects, and dosage and administration of tramadol are reviewed."	( Tramadol: a new centrally acting analgesic. Han, NH; Lewis, KS, 1997)	1.96
" Tramadol showed a dose-response for analgesia in both postsurgical and dental pain patients."	( Single-patient data meta-analysis of 3453 postoperative patients: oral tramadol versus placebo, codeine and combination analgesics. McQuay, JH; Moore, AR, 1997)	1.44
" After 3 weeks' treatment the dosage in both groups remained almost constant for the rest of the 6-week treatment phase (mean daily dose: tramadol 250 to 290mg; clomipramine 59."	( [Treatment of post-herpes zoster pain with tramadol. Results of an open pilot study versus clomipramine with or without levomepromazine]. Göbel, H; Stadler, T, 1997)	0.76
" Patients were randomized into one of four treatment groups for 14 days: placebo, or tramadol dosage titrated at 1, 4, or 10 days to achieve the study target dosage of 200 mg/day."	( Slowing the initial titration rate of tramadol improves tolerability. Ruoff, GE, 1999)	0.8
" Sample pre-treatment of the dosage forms involved dilution or extraction of I with water (for suppositories the extraction was carried out in an ultrasonic bath at 40 degrees C for 10 min)."	( Determination of tramadol in various dosage forms by capillary isotachophoresis. Jokl, V; Polásek, M; Pospísilová, M, 1998)	0.64
" Dose-response relationships show that higher doses of ibuprofen may be particularly effective."	( Postoperative analgesia and vomiting, with special reference to day-case surgery: a systematic review. McQuay, HJ; Moore, RA, 1998)	0.3
" Patients were randomized to one of three groups using a 10-, 16- or a 13-day titration schedule in order to achieve a target dosage of either 200 mg/day (10- and 16-day titration groups) or 150 mg/day (13-day titration group)."	( Slowing the titration rate of tramadol HCl reduces the incidence of discontinuation due to nausea and/or vomiting: a double-blind randomized trial. Kamin, M; Olson, W; Petrone, D, 1999)	0.59
"To demonstrate that in patients receiving naproxen for the pain of osteoarthritis (OA), the addition of tramadol will allow a reduction in the naproxen dosage without compromising pain relief."	( Tramadol allows reduction of naproxen dose among patients with naproxen-responsive osteoarthritis pain: a randomized, double-blind, placebo-controlled study. Kamin, M; Olson, WH; Schnitzer, TJ, 1999)	1.96
" The MEND was defined as 250 mg above the naproxen daily dosage at which pain relief was no longer adequate."	( Tramadol allows reduction of naproxen dose among patients with naproxen-responsive osteoarthritis pain: a randomized, double-blind, placebo-controlled study. Kamin, M; Olson, WH; Schnitzer, TJ, 1999)	1.75
"040) in the treatment effect between the naproxen responders and nonresponders, thus demonstrating a difference in the way responders and nonresponders react to a decrease in naproxen dosage after the addition of tramadol."	( Tramadol allows reduction of naproxen dose among patients with naproxen-responsive osteoarthritis pain: a randomized, double-blind, placebo-controlled study. Kamin, M; Olson, WH; Schnitzer, TJ, 1999)	1.93
"In patients with painful OA of the knee responding to naproxen 1,000 mg/day, the addition of tramadol 200 mg/day allows a significant reduction in the dosage of naproxen without compromising pain relief."	( Tramadol allows reduction of naproxen dose among patients with naproxen-responsive osteoarthritis pain: a randomized, double-blind, placebo-controlled study. Kamin, M; Olson, WH; Schnitzer, TJ, 1999)	1.97
"This report reviews the causes of ocular pain and discusses the pharmacology, pharmacokinetics, efficacy, adverse effects, and dosage of tramadol, a novel non-narcotic oral analgesic."	( Analgesics in ophthalmic practice: a review of the oral non-narcotic agent tramadol. Barkin, RL; Gaynes, BI, 1999)	0.74
" Four patients had to be excluded from the study (2 postoperative confusion, 1 elevated piritramid dosage caused by chronic pain therapy, 1 stressed by PCA pump handling)."	( Pain therapy following joint replacement.A randomized study of patient-controlled analgesia versus conventional pain therapy. Forst, J; Forst, R; Thamm, P; Wolff, S, 1999)	0.3
" There was no dose-response relationship for bromfenac."	( Comparison of tilidine/naloxone, tramadol and bromfenac in experimental pain: a double-blind randomized crossover study in healthy human volunteers. Högger, P; Rohdewald, P, 1999)	0.58
"Various monoolein-water systems containing tramadol HCl, a potent analgesic, were formulated to obtain sustained-release dosage forms which could be administered by subcutaneous, intramuscular or intrathecal injections."	( In vitro/in vivo characterization of a tramadol HCl depot system composed of monoolein and water. Fontaine, J; Malonne, H; Moës, A, 2000)	0.84
" This dosage of paracetamol is lower than the current recommended dosage, which is 40 mg kg(-1) loading dose followed by 20 mg kg(-1) 8 h(-1)."	( Double-blind randomized study of tramadol vs. paracetamol in analgesia after day-case tonsillectomy in children. Dort, JP; Pendeville, PE; Veyckemans, F; Von Montigny, S, 2000)	0.59
" Simple hints are given how to best use tramadol by selecting the right patients and choosing the right dosing strategy."	( Treatment of pain in osteoarthritis. Pavelka, K, 2000)	0.57
"A prophylactic approach to the management of postoperative pain is described: ketoprofen, a nonsteroid antiinflammatory drug, was used, which possesses numerous advantages and a variety of dosage forms."	( [Ketoprofen (ketonal): a drug for preventing and treating postoperative pain]. Beresnev, VA; Dolgopolova, TV; Osipova, NA; Vetsheva, MS, )	0.13
" We concluded that both tramadol and meperidine show a significantly faster response rate in the treatment of postepidural anesthetic shivering when compared with amitriptyline in the dosage used; tramadol had a decreased incidence of somnolence when compared with meperidine."	( A comparison of tramadol, amitriptyline, and meperidine for postepidural anesthetic shivering in parturients. Chu, KS; Tsai, YC, 2001)	0.96
" This article will address the safety and efficacy of acetaminophen, aspirin, and ibuprofen independently and in combination with currently available prescription dosage forms with a focus on pharmacology, pharmacotherapeutics, pharmacodynamics, and pharmacokinetics, including drug interactions at the CYP450 system."	( Acetaminophen, aspirin, or Ibuprofen in combination analgesic products. Barkin, RL, )	0.13
" After a multiple dosage schedule, the serum concentrations of (+)-trans-T, (-)-trans-T, (+)-M1, and (-)-M1 were determined in serum by high performance capillary electrophoresis (HPCE)."	( Pharmacokinetics of enantiomers of trans-tramadol and its active metabolite, trans-O-demethyltramadol, in human subjects. Hou, YN; Liu, HC; Liu, TJ; Yang, YY, 2001)	0.58
" This dosage strategy will also minimise the usual opioid-type adverse effects encountered with tramadol."	( Tramadol in musculoskeletal pain--a survey. Reig, E, 2002)	1.98
"An extraction and measurement technique (gas chromatograph equipped with a nitrogen phosphorus detector) was used to measure plasma and brain levels of tramadol and M1 at intervals 10-300 min after oral dosing of tramadol hydrochloride to mice and rats."	( Differential tramadol and O-desmethyl metabolite levels in brain vs. plasma of mice and rats administered tramadol hydrochloride orally. Borenstein, MR; Codd, EE; Coogan, TP; Desai-Krieger, D; Liao, S; Raffa, RB; Stone, DJ; Tao, Q, 2002)	0.88
" The two methods have been applied successfully to commercial capsule and ampoule dosage form."	( Kinetic spectrophotometric determination of tramadol hydrochloride in pharmaceutical formulation. Abdellatef, HE, 2002)	0.58
" The efficacy of the OD tramadol over the 24 h dosing interval was confirmed by the low sleep disturbance, absence of "end of dose" effects in morning pain scores, and low escape medication use."	( A comparison of once-daily tramadol with normal release tramadol in the treatment of pain in osteoarthritis. Adler, L; McDonald, C; O'Brien, C; Wilson, M, 2002)	0.92
" However, OD tramadol offers the advantage of a reduced dosing regimen, which is especially valuable in the elderly population."	( A comparison of once-daily tramadol with normal release tramadol in the treatment of pain in osteoarthritis. Adler, L; McDonald, C; O'Brien, C; Wilson, M, 2002)	0.98
"To investigate the influence of dosing time on acute toxicity, action and pharmacokinetics of tramadol in mice to find the circadian rhythms of the drug."	( [Chronopharmacology of tramadol in mice]. Liu, XP; Song, JG, 2001)	0.84
"Intraarterial administration of lidocaine before and during chemoembolization is a safe and effective method for preventing or reducing peri- and post-procedural pain and dosage of narcotic analgesics in patients with HCC."	( Chemoembolization for hepatocellular carcinoma: effect of intraarterial lidocaine in peri- and post-procedural pain and hospitalization. Giojelli, A; Romano, M; Salvatore, M; Tamburrini, O, 2003)	0.32
" Tramadol was administered at an average dosage of 275."	( Tramadol in post-herpetic neuralgia: a randomized, double-blind, placebo-controlled trial. Boureau, F; Kabir-Ahmadi, M; Legallicier, P, 2003)	2.67
" The electrochemical methods developed were successfully applied to the determination of tramadol in pharmaceutical dosage forms, without any pre-treatment of the samples."	( Development of electrochemical methods for determination of tramadol--analytical application to pharmaceutical dosage forms. Borges, F; Delerue-Matos, C; Garrido, EM; Garrido, JM, 2003)	0.78
"200 mg daily dosage of sustained release tramadol could be a good option for pain control in musculoskeletal and postoperative pain conditions, especially when non-steroidal anti-inflammatory drugs are contraindicated."	( Three-week open multi-centre study of sustained-release tramadol in various pain conditions. Bernik, N; Curković, B, 2003)	0.83
" Dose-response curves (s."	( Interaction between metamizol and tramadol in a model of acute visceral pain in rats. Planas, E; Pol, O; Poveda, R; Puig, MM; Romero, A; Sánchez, S, 2003)	0.6
" Likewise, if kidney (creatinine clearance below 30 ml/min) or hepatic function is severely impaired, some dosage reduction (approximately by 50%) or extension of the dosage interval should be considered."	( Tramadol--the impact of its pharmacokinetic and pharmacodynamic properties on the clinical management of pain. Klotz, U, 2003)	1.76
"To compare the pharmacokinetic profile of a new modified release formulation of tramadol (Tramadol LP 200 mg, SMB Technology, Marche-en-Famenne, Belgium) with that of an immediate release capsule (Topalgic) 50 mg, Grünenthal, Aachen, Germany) after single and multiple dosing and to assess the potential effect of food on its relative bioavailability."	( Pharmacokinetic evaluation of a new oral sustained release dosage form of tramadol. De Niet, S; Lebrun, S; Malonne, H; Sereno, A; Sonet, B; Streel, B; Vanderbist, F, 2004)	0.78
" Thus, the mean AUC infinity of (+/-)tramadol obtained after multiple dosing were 4611 +/- 1944 and 5105 +/- 2101 ngh ml-1 after Topalgic 4 x 50mg and Tramadol LP 200 mg, respectively (95%CI 102-123%)."	( Pharmacokinetic evaluation of a new oral sustained release dosage form of tramadol. De Niet, S; Lebrun, S; Malonne, H; Sereno, A; Sonet, B; Streel, B; Vanderbist, F, 2004)	0.83
" Mean total pain relief and the sum of pain intensity difference were also similar in the early period after dosing (0-4 hours)."	( Onset of analgesia and analgesic efficacy of tramadol/acetaminophen and codeine/acetaminophen/ibuprofen in acute postoperative pain: a single-center, single-dose, randomized, active-controlled, parallel-group study in a dental surgery pain model. Cha, IH; Jung, YS; Kim, DK; Kim, HJ; Kim, MK; Lee, EW, 2004)	0.58
"5 mg/kg of the study drug was injected and this dosage was added to the total amount."	( The postoperative analgesic effect of tramadol when used as subcutaneous local anesthetic. Altunkaya, H; Babuccu, O; Demirel, CB; Hosnuter, M; Kargi, E; Ozer, Y; Ozkocak, I, 2004)	0.59
" The effects of individual and fixed-ratio combinations of locally (subcutaneous) and systemically (intraperitoneal) dosed tramadol were evaluated using the formalin test in rats."	( Evidence of self-synergism in the antinociceptive effect of tramadol in rats. Aguirre-Bañuelos, P; Arellano-Guerrero, A; de Pozos-Guillén, AJ; Hoyo-Vadillo, C; Pérez-Urizar, J, 2004)	0.77
" In the second part, a 40:3 tramadol:morphine dosing ratio was used."	( The median effective dose of tramadol and morphine for postoperative patients: a study of interactions. Benhamou, D; Marcou, TA; Marque, S; Mazoit, JX, 2005)	0.91
"Two newly developed simple and sensitive methods for determination of tramadol hydrochloride in ampoule dosage forms were described and validated."	( Determination of tramadol hydrochloride in ampoule dosage forms by using UV spectrophotometric and HPLC-DAD methods in methanol and water media. Kadioğlu, Y; Küçük, A, 2005)	0.9
" Dosage ranged from a taste amount to 5000 mg."	( Tramadol exposures reported to statewide poison control system. Albertson, TE; Alsop, JA; Marquardt, KA, 2005)	1.77
"It is concluded that paroxetine at a dosage of 20 mg once daily for 3 consecutive days significantly inhibits the metabolism of tramadol to its active metabolite M1 and reduces but does not abolish the hypoalgesic effect of tramadol in human experimental pain models, particularly in opioid-sensitive tests."	( Paroxetine, a cytochrome P450 2D6 inhibitor, diminishes the stereoselective O-demethylation and reduces the hypoalgesic effect of tramadol. Brøsen, K; Enggaard, TP; Laugesen, S; Pedersen, RS; Sindrup, SH, 2005)	0.74
" The maximum mean differences from placebo after dosing with 50, 100 and 150 mg tramadol-HCL were -0."	( The effects of tramadol on static and dynamic pupillometry in healthy subjects--the relationship between pharmacodynamics, pharmacokinetics and CYP2D6 metaboliser status. Fliegert, F; Göhler, K; Kurth, B, 2005)	0.91
" Tramadol has not been compared with codeine, ibuprofen, or correctly dosed paracetamol (step-1 analgesic)."	( Tramadol oral solution: new drug. Poorly evaluated and potentially dangerous in children. , 2005)	2.68
" Despite this difference in pharmacokinetics between neonates and adults, the intramuscular application of tramadol at the recommended dosage range during delivery appears to effective in the relief of labour pain."	( Different pharmacokinetics of tramadol in mothers treated for labour pain and in their neonates. Claahsen-van der Grinten, HL; Kollée, LA; Sporken, JM; van den Berg, PP; Verbruggen, I, 2005)	0.83
" Appropriately dosed and monitored use of opioids for OA pain, when more conservative methods have failed, has potentially fewer life-threatening complications associated with it than the more commonly and often less successfully employed pharmacotherapeutic approaches to care."	( The use of opioids in the treatment of osteoarthritis: when, why, and how? Bajwa, ZH; Goodwin, JL; Kraemer, JJ, 2005)	0.33
" Dose-response curves were also obtained with tramadol combined with ondansetron or droperidol at 1:1 fixed ratios."	( Interaction between tramadol and two anti-emetics on nociception and gastrointestinal transit in mice. Dürsteler, C; Fernandez, V; Mases, A; Pol, O; Puig, MM, 2006)	0.92
" In clinical practice, combinations are usually given at the above-mentioned dosage three to four times a day."	( Comparative trial of tramadol/paracetamol and codeine/paracetamol combination tablets on the vigilance of healthy volunteers. Dubray, C; Estrade, M; Pickering, G, 2005)	0.65
" Treatment response was higher for tramadol/APAP than a placebo at 2 hours after dosing (55."	( Tramadol/acetaminophen for the treatment of acute migraine pain: findings of a randomized, placebo-controlled trial. Fisher, AC; Freitag, FG; Hewitt, DJ; Jordan, DM; Kudrow, DB; Rosenthal, NR; Rozen, TD; Silberstein, SD, )	1.85
" The effect of an IV injection of 100 mg tramadol on experimental pain was studied 15-90 min after dosing in volunteers, 10 extensive metabolizers with CYP2D6 and 10 poor metabolizers without CYP2D6 in 2 placebo-controlled trials."	( The analgesic effect of tramadol after intravenous injection in healthy volunteers in relation to CYP2D6. Arendt-Nielsen, L; Brøsen, K; Enggaard, TP; Ossig, J; Poulsen, L; Sindrup, SH, 2006)	0.91
" Starting treatment with tramadol SR capsules at a dosage of 50 mg twice daily with subsequent dose escalation resulted in improved tolerability in patients with moderate to severe chronic pain."	( Tramadol sustained-release capsules. Keating, GM, 2006)	2.08
" In endothelium-intact rings precontracted with phenylephrine with or without naloxone, dose-response curves for acetylcholine, histamine, and calcium ionophore A23187 were generated in the presence and absence of tramadol (racemic, R(-) and S(+))."	( A supraclinical dose of tramadol stereoselectively attenuates endothelium-dependent relaxation in isolated rat aorta. Chang, KC; Choi, JY; Chung, YK; Lee, HK; Park, KE; Shin, IW; Sohn, JT, 2006)	0.83
" Once-daily tramadol offers the advantage of a reduced dosing regimen that improves patient compliance."	( Once-daily tramadol in rheumatological pain. Coluzzi, F; Mattia, C, 2006)	1.1
" A 30% dosage reduction from warfarin 60 to 42 mg/week was eventually needed."	( Successful anticoagulation and continuation of tramadol therapy in the setting of a tramadol-warfarin interaction. Dumo, PA; Kielbasa, LA, 2006)	0.59
" The antinociceptive efficacies were evaluated using several dose-response curves and time courses."	( Evaluation of the antinociceptive effect of Rosmarinus officinalis L. using three different experimental models in rodents. Déciga-Campos, M; González-Trujano, ME; Guevara-Fefer, P; López-Muñoz, FJ; Martínez, AL; Moreno, J; Peña, EI, 2007)	0.34
" This modeling and simulation analysis was conducted to support dosing recommendations for switching patients receiving immediate-release tramadol (tramadol IR) to tramadol ER."	( Pharmacokinetic model and simulations of dose conversion from immediate- to extended-release tramadol. Brett, V; Danyluk, AP; Moskovitz, BL; Murthy, BP; Skee, DM; Vorsanger, GJ, 2007)	0.76
" The mean dosage of meperidine used was 76."	( The effect of tramadol or clonidine added to intraperitoneal bupivacaine on postoperative pain in total abdominal hysterectomy. Karamanlioglu, B; Memis, D; Pamukçu, Z; Tükenmez, B; Turan, A, )	0.49
" This paper presents a synthetic review of the present knowledge regarding the efficacy, dosage and possible routes of administration of tramadol to children in the postoperative period."	( [Tramadol for acute postoperative pain in children]. Pendeville, PE; Veyckemans, F, 2007)	1.45
"The effects of tramadol (racemic, R(-) and S(+): 10(-6), 10(-5), 5 x 10(-5) M), and glibenclamide on the levcromakalim dose-response curve were assessed in aortic rings that had been pre-contracted with phenylephrine."	( Inhibitory effect of tramadol on vasorelaxation mediated by ATP-sensitive K+ channels in rat aorta. Chang, KC; Cho, HC; Chung, YK; Lee, HK; Lee, JW; Park, KE; Shin, IW; Sohn, JT, 2007)	1.01
" Diagnosis of inappropriate antidiuretic hormone secretion was based on blood and urinary analysis and dosage of antidiuretic hormone."	( [Hyponatremia due to tramadol]. Algayres, JP; Béchade, D; Coutant, G; Desramé, J; Le Berre, JP; Lecoules, S, 2007)	0.66
"Both gabapentin and pregabalin are approved for the management of postherpetic neuralgia (PHN), although dosing and pharmacokinetic differences between these medications may affect their use in actual practice."	( A retrospective evaluation of the use of gabapentin and pregabalin in patients with postherpetic neuralgia in usual-care settings. Gore, M; Sadosky, A; Stacey, B; Tai, KS, 2007)	0.34
" Thirty-five patients were treated conventionally with increasing transdermal fentanyl dosage as required (group F) and 35 patients received oral tramadol added to their transdermal fentanyl before each increment of the transdermal opioid dosage (group T)."	( Improved cancer pain treatment using combined fentanyl-TTS and tramadol. Aloisio, L; Bajocco, C; Ciccozzi, A; Coaccioli, S; Colangeli, A; Marinangeli, F; Paladini, A; Varrassi, G, 2007)	0.78
" Tramadol once-daily formulations are more effective than placebo and at least as effective and well tolerated as immediate-release formulations in the treatment of pain due to osteoarthritis, and offer a reduced dosing regimen, which is especially valuable in elderly patients."	( Tramadol extended-release formulations in the management of pain due to osteoarthritis. Mongin, G, 2007)	2.69
" Because once-daily tramadol ER results in less frequent fluctuations in plasma concentrations than equivalent daily doses of short-acting tramadol, it may benefit patients experiencing pain throughout the dosing interval."	( Extended-release Tramadol (ULTRAM ER): a pharmacotherapeutic, pharmacokinetic, and pharmacodynamic focus on effectiveness and safety in patients with chronic/persistent pain. Barkin, RL, )	0.79
"Time-point of administration does not have any relevant impact on the rate and extent of absorption in the investigated dosage form."	( [Importance of the formulation for a chronopharmacologically optimised way of pain therapy. Results of a comparative bioavailability study of tramadol extended-release capsules after single-dose evening versus morning administration]. Blume, H; Schug, B; Vanderbist, F; Warnke, A, 2008)	0.55
" Intrathecal pumping higher dosage tramadol (50microg/h) suppresses T lymphocyte proliferation and alteres T lymphocyte subset phenotype but does not affect NK cell activity."	( [Effect of intrathecal pumping tramadol on the immune function in rats with formalin pain]. Cai, J; Guo, QL; Wang, E; Wang, YC; Xu, DM; Yang, HW; Zou, WY, 2008)	0.91
"Tramadol has been reported to cause seizures in therapeutic dosing and in overdose."	( Pediatric tramadol ingestion resulting in seizurelike activity: a case series. Feldman, KW; Mazor, SS; Sotero, M; Sugar, NF, 2008)	2.19
"Drugs were tested in a repeated dosing paradigm (four daily injections)."	( Experimental studies of potential analgesics for the treatment of chemotherapy-evoked painful peripheral neuropathies. Bennett, GJ; Naso, L; Xiao, W, )	0.13
"Neonatal drug dosing needs to be based on the physiological characteristics of the newborn, the pharmacokinetic parameters of the drug and has to take maturational aspects of drug disposition into account."	( Neonatal clinical pharmacology: recent observations of relevance for anaesthesiologists. Allegaert, K; de Hoon, J; Naulaers, G; Van De Velde, M, 2008)	0.35
" Patients were randomized in a 1:1 ratio to receive either low-dose 7-day buprenorphine patches (patch strengths of 5, 10, and 20 microg/h, with a maximum dosage of 20 microg/h) or twice-daily prolonged-release tramadol tablets (tablet strengths of 75, 100, 150, and 200 mg, with a maximum dosage of 400 mg/d) over a 12-week open-label treatment period."	( Efficacy and safety of low-dose transdermal buprenorphine patches (5, 10, and 20 microg/h) versus prolonged-release tramadol tablets (75, 100, 150, and 200 mg) in patients with chronic osteoarthritis pain: a 12-week, randomized, open-label, controlled, pa Berggren, AC; Karlsson, M, 2009)	0.75
" Statistical analyses, based on conventional bioequivalence approach, revealed no evidence of any impact of the time-point of administration on the biopharmaceutical performance of the dosage form investigated here."	( Significance of the biopharmaceutical properties of tramadol sustained-release formulations for chrono-pharmacologically optimized treatment of pain from various sources. Blume, H; Schug, B; Vanderbist, F; Warnke, A, 2009)	0.6
"Two parallel, placebo-controlled phase III clinical trials were analyzed; patients were randomized to a fixed dosage of Tramadol Contramid once a day (OAD) 100, 200, and 300 mg daily, or placebo."	( Women with pain due to osteoarthritis: the efficacy and safety of a once-daily formulation of tramadol. Bouchard, S; Kean, WF; Roderich Gossen, E, 2009)	0.78
"023) treatment arms; however, the 200-mg dosage was not significant (53."	( Women with pain due to osteoarthritis: the efficacy and safety of a once-daily formulation of tramadol. Bouchard, S; Kean, WF; Roderich Gossen, E, 2009)	0.57
"To assess clinical equivalence of 20 mg controlled-release oxycodone (Oxygesic; Mundipharma, Limburg, Germany) and 200 mg controlled-release tramadol (Tramal long; Grunenthal, Aachen, Germany) on a 12-hour dosing schedule in a randomized, double-blinded study of 54 ASA I-III physical status (American Society of Anesthesiologists classification of physical status) patients undergoing surgery for breast cancer."	( Clinical equivalence of controlled-release oxycodone 20 mg and controlled-release tramadol 200 mg after surgery for breast cancer. Dagtekin, O; Kampe, S; Landwehr, S; Shaheen, S; Warm, M; Wolter, K, 2009)	0.78
" After single-dose administration, the mean tramadol concentration at 1 hour postdose was within the range associated with analgesic efficacy (>100 ng/mL), and the mean concentration remained above this level for the remainder of the dosing interval."	( Comparative pharmacokinetics of a once-daily tramadol extended-release tablet and an immediate-release reference product following single-dose and multiple-dose administration. Ferreira, MM; Fradette, C; Karhu, D; Potgieter, MA; Terblanché, J, 2010)	0.88
"Coating, as a processing technique, applied to active pharmaceutical ingredient (API) crystals or particles (carriers) with an appropriate polymer allows to obtain a modified-release pharmaceutical dosage form."	( Hot tabletting of slow-release tramadol hydrochloride microcapsules with cores obtained via compaction. Jakubowska, I; Mazgalski, J; Sawicki, W, 2010)	0.65
"Multi-unit dosage forms can be obtained in a relatively simple way by combining three processes: (i) obtaining TH microcapsule cores by compaction, (ii) coating, and (iii) hot tabletting."	( Hot tabletting of slow-release tramadol hydrochloride microcapsules with cores obtained via compaction. Jakubowska, I; Mazgalski, J; Sawicki, W, 2010)	0.65
" The aim of this article is to summarize the data regarding pharmacodynamics, pharmacokinetics, possible drug interactions, adverse effects, dosing guidelines, equipotency with other opioid analgesics and clinical studies comparing efficacy, adverse reactions and safety of tramadol to other opioids in cancer pain treatment."	( Tramadol as an analgesic for mild to moderate cancer pain. Leppert, W, )	1.75
" Oral tapentadol HCI is administered in doses of 50 to 100 mg every four to six hours (dose and dosing interval being selected on the basis of pain intensity)."	( Is tapentadol an advance on tramadol? Guay, DR, 2009)	0.65
"The determination of the pharmacokinetic parameters of tramadol in plasma and a better characterization of its metabolites after oral administration to horses is necessary to design dosage regimens to achieve target plasma concentrations that are associated with analgesia."	( Determination of oral tramadol pharmacokinetics in horses. Cox, S; Doherty, T; Villarino, N, 2010)	0.92
" To determine the pharmacokinetics of tramadol and its major metabolite O-desmethyltramadol (M1) in eagles, 6 bald eagles (Haliaeetus leucocephalus) were each dosed with tramadol administered intravenously (4 mg/kg) and orally (11 mg/kg) in a crossover study."	( Pharmacokinetics of intravenous and oral tramadol in the bald eagle (Haliaeetus leucocephalus). Cox, SK; Jones, MP; Martin-Jimenez, T; Souza, MJ, 2009)	0.89
" The combination of diclofenac sodium and metamizole sodium is acceptable, although, at a lower dosage of metamizole, the duration of analgesia is shortened."	( Evidence-based intravenous pain treatment with analgesic infusion regimens. Cihal, P; Kamyar, MR; Lemmens-Gruber, R; Nemec, K; Timin, E, 2010)	0.36
" In Phase 2, the dose-response curve shifted to the left with the combination of tramadol and each dose of caffeine."	( Tramadol and caffeine produce synergistic interactions on antinociception measured in a formalin model. Carrillo-Munguía, N; Díaz-Reval, MI; González-Trujano, ME; Martínez-Casas, M, 2010)	2.03
" In both (placebo and morphine pellets), dose-response curves for M, FEN and TRM, individually and combined were obtained, and the doses that produced 50% inhibition (ED(50)) were determined."	( Antinociceptive effects of morphine, fentanyl, tramadol and their combination, in morphine-tolerant mice. Miranda, HF; Puig, MM; Romero, A, 2010)	0.62
"This casuistic reports on a 59-year-old pain patient taking normal dosage Tramadol as analgetic drug, who suffered from chronic dizziness leading to immobilisation for more than 9 months."	( [Chronic dizziness in a pain patient--pharmacogenomic identification of tramadol as cause]. Barth, J; Eichhorn, A, 2010)	0.82
" The dosage of the drugs was unknown."	( Distribution of metoprolol, tramadol, and midazolam in human autopsy material. Arenz, N; Goltz, L; Kirch, W; Oertel, R; Pietsch, J; Zeitz, SG, 2011)	0.66
" Two sensitive, selective, and rapid spectrophotometric methods are described for the determination of tramadol in its dosage forms and in spiked human urine."	( Use of two sulfonthalein dyes in the extraction-free spectrophotometric assay of tramadol in dosage forms and in spiked human urine based on ion-pair reaction. Basavaiah, K; Rajendraprasad, N; Ramesh, PJ; Revannasiddappa, HD; Vinay, KB; Xavier, CM, 2012)	0.82
"An evaluation of dose-response relationship and an attempt to define predictive factors."	( Radiotherapy of painful vertebral hemangiomas: the single center retrospective analysis of 137 cases. Miszczyk, L; Tukiendorf, A, 2012)	0.38
"The aim of this study was to explore the pharmacokinetic profiles of the new ER tramadol/acetaminophen fixed-dose combination and compare them with those of a conventional immediate-release (IR) formulation after multiple dosing as a Phase I clinical exploratory trial."	( Pharmacokinetics of extended-release versus conventional tramadol/acetaminophen fixed-dose combination tablets: an open-label, 2-treatment, multiple-dose, randomized-sequence crossover study in healthy korean male volunteers. Cho, JY; Chung, YJ; Jang, IJ; Kim, TE; Shin, HS; Shin, SG; Yi, S; Yoon, SH; Yu, KS, 2011)	0.84
" dosage with a large inter-subject variation."	( Pharmacokinetics of tramadol and its major metabolites in alpacas following intravenous and oral administration. Boothe, DM; Duran, SH; Edmondson, MA; Ravis, WR; Stewart, AJ, 2012)	0.7
" Dose-response curves for DEX and TRM, individually and combined in a 1 : 1 proportion based on their potency were obtained, and the doses that produced a 50% inhibition calculated."	( Antinociceptive and anti-exudative synergism between dexketoprofen and tramadol in a model of inflammatory pain in mice. Miranda, HF; Puig, MM; Romero, MA, 2012)	0.61
" However, dosing and differential effects on peripheral and central hyperalgesia are still to be determined."	( Dose response of tramadol and its combination with paracetamol in UVB induced hyperalgesia. Gustorff, B; Margeta, K; Ortner, CM; Schulz, M; Steiner, I, 2012)	0.72
" Benefits of the compounded tramadol product over the commercially available film-coated tablets include palatability and more accurate dosing for the feline species."	( Case studies of compounded Tramadol use in cats. Boggess, D; Clark, J; Fackler, B; Jordan, D; Pinelli, C; Ray, J, )	0.72
" Three OIH types were defined: 1) in the context of maintenance dosing and withdrawal, 2) at very high or escalating doses, and 3) at ultra-low doses."	( Tramadol induced paradoxical hyperalgesia. Cho, SY; Choi, JI; Kim, WM; Lee, HG; Lee, SH; Yoon, MH, 2013)	1.83
"We compared an approach using scheduled analgesic dosing with as-needed analgesic dosing in patients after hip fracture surgery, to compare these approaches in terms of (1) resting and dynamic pain intensity, (2) postoperative patient mobility, and (3) functional end points."	( Scheduled analgesic regimen improves rehabilitation after hip fracture surgery. Cheung, LP; Chin, RP; Ho, CH, 2013)	0.39
" All data were recorded concerning the initial and total dosage of analgesic and the presence of complications within 24 hrs."	( [A comparison of the effects of intraoperative tramadol and ketamine usage for postoperative pain relief in patients undergoing tonsillectomy]. Çelik, JB; Kara, I; Sizer, Ç; Topal, A, 2013)	0.65
" Paracetamol dosage was significantly higher in the control group (p<0."	( [A comparison of the effects of intraoperative tramadol and ketamine usage for postoperative pain relief in patients undergoing tonsillectomy]. Çelik, JB; Kara, I; Sizer, Ç; Topal, A, 2013)	0.65
"Tramadol hydrochloride was administered to each parrot at a dosage of 30 mg/kg, PO, every 12 hours for 5 days."	( Pharmacokinetics of repeated oral administration of tramadol hydrochloride in Hispaniolan Amazon parrots (Amazona ventralis). Cox, S; Gerhardt, L; Souza, MJ, 2013)	2.08
"On the basis of these results and modeling of the data, tramadol at a dosage of 30 mg/kg, PO, will likely need to be administered every 6 to 8 hours to maintain therapeutic plasma concentrations in Hispaniolan Amazon parrots."	( Pharmacokinetics of repeated oral administration of tramadol hydrochloride in Hispaniolan Amazon parrots (Amazona ventralis). Cox, S; Gerhardt, L; Souza, MJ, 2013)	0.89
" The purpose of this study was to investigate the antinociceptive and constipation effects of tramadol and metamizole alone or in combination in rats and to discern among the types of drug interactions that exist using dose-response curves and an isobolographic analysis."	( Enhancement of antinociception but not constipation by combinations containing tramadol and metamizole in arthritic rats. Bravo, G; Déciga-Campos, M; Domínguez-Ramírez, AM; Guevara-López, U; López-Muñoz, FJ; Moreno-Rocha, LA, 2013)	0.84
" Each patient's demographic and clinical characteristics, the need for ventilatory support, the use and dosage of medications, the number of nursing staff per bed, the time elapsed from admission to the intensive care unit until the effective start of enteral feeding, and the causes for nonadministration were recorded."	( Nurse to bed ratio and nutrition support in critically ill patients. Azevedo, LC; Bafi, AT; Castro, I; Freitas, FG; Honda, CK; Machado, FR; Mazza, BF; Nascente, AP; Stanich, P, 2013)	0.39
" Conclusion Achievement of daily calorie goals was inadequate, and the main factors associated with this failure were the use and dosage of midazolam and the number of nurses available."	( Nurse to bed ratio and nutrition support in critically ill patients. Azevedo, LC; Bafi, AT; Castro, I; Freitas, FG; Honda, CK; Machado, FR; Mazza, BF; Nascente, AP; Stanich, P, 2013)	0.39
"The present study examines how drug's inherent properties and product design influence the evaluation and applications of in vitro-in vivo correlation (IVIVC) for modified-release (MR) dosage forms consisting of extended-release (ER) and immediate-release (IR) components with bimodal drug release."	( Influence of drug property and product design on in vitro-in vivo correlation of complex modified-release dosage forms. Duan, JZ; Li, X; Qiu, Y, 2014)	0.4
" Individual dose-response curves of the antinociceptive effect of these compounds were built to calculate the ED50, as well as the pharmacological interaction, by using isobolographic analysis."	( Isobolographic analysis of the antinociceptive interaction between ursolic acid and diclofenac or tramadol in mice. Cortés, A; Déciga-Campos, M; Díaz-Reval, I; González-Trujano, ME; Pellicer, F, 2014)	0.62
" Blood samples were collected prior to dosing and up to 72h after drug intake."	( Pharmacogenetic aspects of tramadol pharmacokinetics and pharmacodynamics after a single oral dose. Bastami, S; Haage, P; Kronstrand, R; Kugelberg, FC; Uppugunduri, S; Zackrisson, AL, 2014)	0.7
" When comparing all three groups, a statistically significant dose-response relationship was seen for present, average and worst pain intensity after 8 h and on the following morning."	( Dexamethasone for pain after outpatient shoulder surgery: a randomised, double-blind, placebo-controlled trial. Bjørnholdt, KT; Mønsted, PN; Nikolajsen, L; Søballe, K, 2014)	0.4
"Although our data supported a dose-response relationship, increasing the dexamethasone dose from 8 to 40 mg did not improve analgesia significantly after outpatient shoulder surgery."	( Dexamethasone for pain after outpatient shoulder surgery: a randomised, double-blind, placebo-controlled trial. Bjørnholdt, KT; Mønsted, PN; Nikolajsen, L; Søballe, K, 2014)	0.4
" These results indicate that the same dosing regimens for subcutaneous tramadol administration may therefore be used in both healthy subjects and severely ill patients."	( Pharmacokinetics of tramadol after subcutaneous administration in a critically ill population and in a healthy cohort. Chapman, MJ; Dooney, NM; Ludbrook, GL; O'Connor, SN; Ong, J; Ramkumar, T; Somogyi, AA; Sundararajan, K; Upton, RN, 2014)	0.96
" Increased dosing might result in a ceiling effect, and thus less analgesia than expected."	( Nalbuphine for postoperative pain treatment in children. Pogatzki-Zahn, E; Reichl, SU; Schnabel, A; Zahn, PK, 2014)	0.4
"Decomposed bone and plasma samples of rats exposed to tramadol (TRAM) under different dosing patterns were analyzed."	( Analysis of tramadol and O-desmethyltramadol in decomposed skeletal tissues following acute and repeated tramadol exposure by gas chromatography mass spectrometry. Watterson, JH; Wiebe, TR, 2014)	1.03
" 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)	0.88
"The aim of this study was an in vitro - in vivo evaluation of a new oral dosage form of tramadol hydrochloride (TH), controlled-release capsules filled with coated pellets, 100 mg (TC), compared to the sustained release tablets, Tramal Retard, 100 mg (TR)."	( In vitro - in vivo evaluation of a new oral dosage form of tramadol hydrochloride--controlled-release capsules filled with coated pellets. Balcerkiewicz, M; Grabowski, T; Grześkowiak, E; Mazgalski, J; Sawicki, W; Szkutnik-Fiedler, D; Urjasz, H, )	0.6
" There was no difference in the mean frequency or dosage of rescue medication required by both groups, and the majority of patients in both the TA-ER and TA-IR groups rated their pain improvement as 'much' or 'somewhat better'."	( A randomized study to compare the efficacy and safety of extended-release and immediate-release tramadol HCl/acetaminophen in patients with acute pain following total knee replacement. Bin, SI; Chang, N; Cho, SD; Choi, CH; Ha, CW; Kang, SB; Kyung, HS; Lee, JH; Lee, MC; Park, YB; Rhim, HY; Seo, SS, 2015)	0.64
"This study was aimed at a biopharmaceutical evaluation of a new oral dosage form of tramadol hydrochloride (TH)--slow release tablets obtained by hot tableting of coated pellets, 100 mg (TP), compared to the conventional slow release tablets, Tramal Retard, 100 mg (TR)."	( Biopharmaceutical evaluation of new slow release tablets obtained by hot tableting of coated pellets with tramadol hydrochloride. Balcerkiewicz, M; Grabowski, T; Grześkowiak, E; Mazgalski, J; Sawicki, W; Szkutnik-Fiedler, D, )	0.57
"8 points (NRS-11, 11-point pain scale, n = 96) at the end of observation, using an average dosage of 218."	( [Conversion to tapentadol PR improves analgesia and quality of life in patients with severe and chronic pain despite using tramadol > 300 mg/d]. Lehmann, U; Richter, U; Waldmann-Rex, S, 2015)	0.62
" The proposed procedure was successfully applied to quantify tramadol and metabolites in real hair samples submitted to our laboratory: three cases of tramadol assumption within the therapeutic dosage (3 × 2 segments) and one case of tramadol abuse in a binge pattern (8 segments)."	( Tramadol chronic abuse: an evidence from hair analysis by LC tandem MS. Ferrari, A; Licata, M; Marchesi, F; Palazzoli, F; Rustichelli, C; Vandelli, D; Verri, P, 2015)	2.1
"Eligible patients were randomized (1:1) to receive low-dose 7-day BTDS (5, 10, and 20 μg/h, maximum dosage of 20 μg/h) or sustained-release tramadol tablets (100 mg, maximum dosage of 400 mg/d) over an 8-week double-blind treatment period (3-week titration, 5-week maintenance)."	( Effectiveness and Safety of Transdermal Buprenorphine Versus Sustained-release Tramadol in Patients With Moderate to Severe Musculoskeletal Pain: An 8-Week, Randomized, Double-Blind, Double-Dummy, Multicenter, Active-controlled, Noninferiority Study. Dai, K; Leng, X; Li, Z; Liu, Y; Lv, H; Yan, X; Yao, C; Zeng, X; Zheng, Y, 2015)	0.85
" Its recommended dosing adjustments, potential ceiling effect, cost, pertinent drug interactions, and risk for significant adverse drug reactions may limit its chronic use in patients with significant pain."	( Tramadol in palliative care #290. Arnold, RM; Pruskowski, J, 2015)	1.86
"5%) injection into the upper lip to characterize the dose-response curve of each individual drug in the orofacial pain test in mice."	( Synergism between tramadol and parecoxib in the orofacial formalin test. Aragon-Martinez, OH; Castañeda-Santana, DI; de la Rosa-Coronado, M; Isiordia-Espinoza, MA; Zapata-Morales, JR, 2015)	0.75
" Recent evidence suggests that on-demand dosing of tramadol is effective at increasing intra-vaginal ejaculatory latency time (IELT) and improving subjective measures of satisfaction."	( Tramadol for the management of premature ejaculation: a timely systematic review. Carson, CC; Coward, RM; Kirby, EW, 2015)	2.11
" Finally, the SOS/umu test showed that the genotoxicity of TRA chlorination products increased with increasing dosage of chlorine, which was mostly attributed to the formation of some chlorine substitution products."	( Chlorination of tramadol: Reaction kinetics, mechanism and genotoxicity evaluation. Chang, Y; Cheng, H; Liu, H; Qu, J; Song, D, 2015)	0.76
" Based on dosing simulations, a dose of 4 mg/kg q8 hr or q12 hr, on average, may represent an adequate compromise, but further studies are needed using a larger sample size."	( PHARMACOKINETICS OF TRAMADOL HYDROCHLORIDE AND ITS METABOLITE O-DESMETHYLTRAMADOL FOLLOWING A SINGLE, ORALLY ADMINISTERED DOSE IN CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS). Barbosa, L; Boonstra, JL; Cox, SK; Gulland, FM; Johnson, SP; Martin-Jimenez, T; Van Bonn, WG, 2015)	0.74
" However, dosage adjustments of tramadol are typically not practiced in the clinic when treating patients who are homozygous extensive metabolizers, heterozygous extensive metabolizers, or poor metabolizers."	( Differential Consequences of Tramadol in Overdosing: Dilemma of a Polymorphic Cytochrome P450 2D6-Mediated Substrate. Srinivas, NR, 2015)	0.99
"Metabolism is an essential factor in the clearance of many drugs and as such plays a major role in the establishment of dosage regimens and withdrawal times."	( Evidence for polymorphism in the cytochrome P450 2D50 gene in horses. Corado, CR; Knych, HK; McKemie, DS; Young, A, 2016)	0.43
" depression), so these results should be complied in analgesic dosage adjustment."	( Impairment in Pain Perception in Adult Rats Lesioned as Neonates with 5.7-Dihydroxytryptamine. Lewkowicz, Ł; Malinowska-Borowska, J; Muchacki, R; Nowak, PG; Szkilnik, R; Żelazko, A, )	0.13
" Here we used a recently validated operant orofacial pain assay to determine dose-response curves for buprenorphine and tramadol when mixed in nut paste and administered to male and female rats."	( Analgesic Activity of Tramadol and Buprenorphine after Voluntary Ingestion by Rats (Rattus norvegicus). Andrutis, KA; Battles, AH; Neubert, JK; Ramirez, HE; Taylor, BF, 2016)	0.96
" Dose-response curves (DRC) and isobolographic analysis were used to confirm their synergistic antihyperalgesic and anti-allodynic responses in a rat neuropathic pain model involving chronic constriction injury of the sciatic nerve and in von Frey and acetone tests."	( The Antinociceptive Effects of Tramadol and/or Gabapentin on Rat Neuropathic Pain Induced by a Chronic Constriction Injury. Corona-Ramos, JN; De la O-Arciniega, M; Déciga-Campos, M; Domínguez-Ramírez, AM; Espinosa-Juárez, JV; Jaramillo-Morales, OA; López-Muñoz, FJ; Medina-López, JR, 2016)	0.72
"The objective of this study was to develop and validate a simple method for estimation of tramadol hydrochloride (TH) in pure and pharmaceutical dosage forms using a colorimeter."	( A simple colorimetric method for estimation of tramadol hydrochloride in pure and tablet dosage forms. Sankar, HK; Thomas, SP, )	0.61
" Drug content estimation and recovery studies carried out on commercial tablet dosage forms demonstrated the accuracy of the method and that excipients do not cause interference."	( A simple colorimetric method for estimation of tramadol hydrochloride in pure and tablet dosage forms. Sankar, HK; Thomas, SP, )	0.39
" This literature review reveals that variants in ABCB1, OPRM1, and COMT have been replicated for opioid dosing and variants in ABCB1 have been replicated for both treatment response and adverse effects."	( Pharmacogenomics and Patient Treatment Parameters to Opioid Treatment in Chronic Pain: A Focus on Morphine, Oxycodone, Tramadol, and Fentanyl. Hall, C; Hotham, E; Lloyd, RA; Suppiah, V; Williams, M, 2017)	0.66
" The pharmacokinetic variables may be used to plan the dosage regime during general anaesthesia."	( Cardiovascular effects and intraoperative pharmacokinetics of tramadol in sheep undergoing spinal surgery. Bellini, L; De Benedictis, GM; De Vito, V; Della Rocca, G; Depase, A; Giorgi, M, 2017)	0.7
" We included information about the number of participants treated and demographic details, type of cancer, drug and dosing regimen, study design (placebo or active control) and methods, study duration and follow-up, analgesic outcome measures and results, withdrawals, and adverse events."	( Tramadol with or without paracetamol (acetaminophen) for cancer pain. Derry, S; Moore, RA; Wiffen, PJ, 2017)	1.9
" One study compared tramadol with placebo and a combination of cobrotoxin, tramadol, and ibuprofen, but the dosing schedule poorly explained."	( Tramadol with or without paracetamol (acetaminophen) for cancer pain. Derry, S; Moore, RA; Wiffen, PJ, 2017)	2.22
" There was a dose-response effect of single and multiple doses of follitropin epsilon on follicular growth, which was shown for the biomarker inhibin B as well as for the mean number and size of follicles."	( A new fully human recombinant FSH (follitropin epsilon): two phase I randomized placebo and comparator-controlled pharmacokinetic and pharmacodynamic trials. Abd-Elaziz, K; Dietrich, B; Duijkers, I; Eckert, K; Goletz, S; Klipping, C; Stöckl, L, 2017)	0.46
" To conclude, tramadol and M1 concentrations were low and variable in dogs after oral dosing of tramadol, even in combination with cimetidine or ketoconazole, but effective concentrations in dogs have not been defined."	( The effects of ketoconazole and cimetidine on the pharmacokinetics of oral tramadol in greyhound dogs. Black, J; KuKanich, B; KuKanich, K, 2017)	1.05
" There was a significant increase in activity with the 2-mg/kg dosage of tramadol, compared with activity when cats received the placebo."	( Evaluation of tramadol for treatment of osteoarthritis in geriatric cats. Guedes, AGP; Johnson, EG; Meadows, JM; Pypendop, BH, 2018)	1.07
"In this study, we tested our working hypothesis that inhibiting the activation of microglia by systemic minocycline treatments can decrease the dosage of local tramadol injection in inflammatory pain."	( Pain-Relieving Effectiveness of Co-Treatment with Local Tramadol and Systemic Minocycline in Carrageenan-Induced Inflammatory Pain Model. Mert, T; Sahin, E; Sahin, M; Yaman, S, 2018)	0.92
" Analysed dosage forms contained cyproheptadine and dexamethasone in concentrations higher than therapeutic doses."	( Determination of synthetic pharmaceutical adulterants in herbal weight gain supplements sold in herb shops, Tehran, Iran. Akhgari, M; Bahmanabadi, L; Bazmi, E; Mousavi, Z; Saberi, N, 2018)	0.48
"The present study involved segmental testing of hair in two clinical cases with known dosage histories."	( Segmental Hair Analysis-Interpretation of the Time of Drug Intake in Two Patients Undergoing Drug Treatment. Johansen, SS; Linnet, K; Nielsen, MKK; Wang, X, 2019)	0.51
"Gabapentin is currently used 'off-label' in children and adolescents with chronic neuropathic pain, and reliable evidence of its effects and optimal dosing are lacking."	( Non-inferiority double-blind randomised controlled trial comparing gabapentin versus tramadol for the treatment of chronic neuropathic or mixed pain in children and adolescents: the GABA-1 trial-a study protocol. Alberti, C; Bonifazi, D; Ceci, A; de Leeuw, TG; de Wildt, SN; Della Pasqua, O; Felisi, M; Kaguelidou, F; Le Roux, E; Lundin, R; Mangiarini, L; Tibboel, D, 2019)	0.74
" In the absence of CYP inhibition (trial A), 20 mg desmetramadol and 50 mg tramadol dosed every 6 hours gave equivalent steady-state (+)-M1, similar adverse events, and analgesia significantly greater than placebo, but equal to each other."	( Desmetramadol Has the Safety and Analgesic Profile of Tramadol Without Its Metabolic Liabilities: Consecutive Randomized, Double-Blind, Placebo- and Active Comparator-Controlled Trials. Johnson, MS; Kahn, SJ; Maeda, DY; Schuler, AD; Searle, SL; Webster, LR; Zebala, JA, 2019)	1.27
" Patients hospitalized for opioid use disorder or those receiving substandard dosing of tramadol were excluded."	( Efficacy of Tramadol for Pain Management in Patients Receiving Strong Cytochrome P450 2D6 Inhibitors. Frost, DA; Kaiser, R; Neugebauer, RE; Soric, MM, 2019)	1.12
" The present study tested the hypothesis that multimodal analgesia with combined ropivacaine wound infiltration and intravenous flurbiprofen axetil after radical thyroidectomy provided better analgesia than a single dosage of tramadol."	( Multimodal analgesia with ropivacaine wound infiltration and intravenous flurbiprofen axetil provides enhanced analgesic effects after radical thyroidectomy: a randomized controlled trial. Li, X; Tan, H; Yang, J; Yu, L, 2019)	0.7
" However, there have not been studies comparing the pharmacokinetics (PK) of IV dosing regimens to that of oral tramadol."	( Comparing the Pharmacokinetics of 2 Novel Intravenous Tramadol Dosing Regimens to Oral Tramadol: A Randomized 3-Arm Crossover Study. Atiee, GJ; Harnett, M; Lu, L; Reines, SA; Ryan, M, 2020)	1.02
" Further research into standardizing the dosing of IPT to optimize its effectiveness and further reduce the additional analgesic requirement is indicated."	( Intraperitoneal Tramadol in Abdominal Surgery: A Systematic Review. Autagavaia, V; Barazanchi, AWH; Hill, AG; MacFater, WS; Otutaha, B; Xia, W, 2020)	0.9
" This method involves manipulating pharmaceutical active ingredients to a suitable dosage and formulation for administration to humans or animals."	( Stability of Extemporaneous Oral Tramadol, Fluoxetine, and Doxycycline Suspensions in SyrSpend SF pH4. Espana, B; Jaquet, C; Joseph-Tornabène, F; Perrot, S; Prouillac, C, )	0.41
"Findings will provide timely information on the safety, efficacy, and optimal dosing of t-PA to treat moderate/severe COVID-19-induced ARDS, which can be rapidly adapted to a phase III trial (NCT04357730; FDA IND 149634)."	( Abbasi, S; Abd El-Wahab, A; Abdallah, M; Abebe, G; Aca-Aca, G; Adama, S; Adefegha, SA; Adidigue-Ndiome, R; Adiseshaiah, P; Adrario, E; Aghajanian, C; Agnese, W; Ahmad, A; Ahmad, I; Ahmed, MFE; Akcay, OF; Akinmoladun, AC; Akutagawa, T; Alakavuklar, MA; Álava-Rabasa, S; Albaladejo-Florín, MJ; Alexandra, AJE; Alfawares, R; Alferiev, IS; Alghamdi, HS; Ali, I; Allard, B; Allen, JD; Almada, E; Alobaid, A; Alonso, GL; Alqahtani, YS; Alqarawi, W; Alsaleh, H; Alyami, BA; Amaral, BPD; Amaro, JT; Amin, SAW; Amodio, E; Amoo, ZA; Andia Biraro, I; Angiolella, L; Anheyer, D; Anlay, DZ; Annex, BH; Antonio-Aguirre, B; Apple, S; Arbuznikov, AV; Arinsoy, T; Armstrong, DK; Ash, S; Aslam, M; Asrie, F; Astur, DC; Atzrodt, J; Au, DW; Aucoin, M; Auerbach, EJ; Azarian, S; Ba, D; Bai, Z; Baisch, PRM; Balkissou, AD; Baltzopoulos, V; Banaszewski, M; Banerjee, S; Bao, Y; Baradwan, A; Barandika, JF; Barger, PM; Barion, MRL; Barrett, CD; Basudan, AM; Baur, LE; Baz-Rodríguez, SA; Beamer, P; Beaulant, A; Becker, DF; Beckers, C; Bedel, J; Bedlack, R; Bermúdez de Castro, JM; Berry, JD; Berthier, C; Bhattacharya, D; Biadgo, B; Bianco, G; Bianco, M; Bibi, S; Bigliardi, AP; Billheimer, D; Birnie, DH; Biswas, K; Blair, HC; Bognetti, P; Bolan, PJ; Bolla, JR; Bolze, A; Bonnaillie, P; Borlimi, R; Bórquez, J; Bottari, NB; Boulleys-Nana, JR; Brighetti, G; Brodeur, GM; Budnyak, T; Budnyk, S; Bukirwa, VD; Bulman, DM; Burm, R; Busman-Sahay, K; Butcher, TW; Cai, C; Cai, H; Cai, L; Cairati, M; Calvano, CD; Camacho-Ordóñez, A; Camela, E; Cameron, T; Campbell, BS; Cansian, RL; Cao, Y; Caporale, AS; Carciofi, AC; Cardozo, V; Carè, J; Carlos, AF; Carozza, R; Carroll, CJW; Carsetti, A; Carubelli, V; Casarotta, E; Casas, M; Caselli, G; Castillo-Lora, J; Cataldi, TRI; Cavalcante, ELB; Cavaleiro, A; Cayci, Z; Cebrián-Tarancón, C; Cedrone, E; Cella, D; Cereda, C; Ceretti, A; Ceroni, M; Cha, YH; Chai, X; Chang, EF; Chang, TS; Chanteux, H; Chao, M; Chaplin, BP; Chaturvedi, S; Chaturvedi, V; Chaudhary, DK; Chen, A; Chen, C; Chen, HY; Chen, J; Chen, JJ; Chen, K; Chen, L; Chen, Q; Chen, R; Chen, SY; Chen, TY; Chen, WM; Chen, X; Chen, Y; Cheng, G; Cheng, GJ; Cheng, J; Cheng, YH; Cheon, HG; Chew, KW; Chhoker, S; Chiu, WN; Choi, ES; Choi, MJ; Choi, SD; Chokshi, S; Chorny, M; Chu, KI; Chu, WJ; Church, AL; Cirrincione, A; Clamp, AR; Cleff, MB; Cohen, M; Coleman, RL; Collins, SL; Colombo, N; Conduit, N; Cong, WL; Connelly, MA; Connor, J; Cooley, K; Correa Ramos Leal, I; Cose, S; Costantino, C; Cottrell, M; Cui, L; Cundall, J; Cutaia, C; Cutler, CW; Cuypers, ML; da Silva Júnior, FMR; Dahal, RH; Damiani, E; Damtie, D; Dan-Li, W; Dang, Z; Dasa, SSK; Davin, A; Davis, DR; de Andrade, CM; de Jong, PL; de Oliveira, D; de Paula Dorigam, JC; Dean, A; Deepa, M; Delatour, C; Dell'Aiera, S; Delley, MF; den Boer, RB; Deng, L; Deng, Q; Depner, RM; Derdau, V; Derici, U; DeSantis, AJ; Desmarini, D; Diffo-Sonkoue, L; Divizia, M; Djenabou, A; Djordjevic, JT; Dobrovolskaia, MA; Domizi, R; Donati, A; Dong, Y; Dos Santos, M; Dos Santos, MP; Douglas, RG; Duarte, PF; Dullaart, RPF; Duscha, BD; Edwards, LA; Edwards, TE; Eichenwald, EC; El-Baba, TJ; Elashiry, M; Elashiry, MM; Elashry, SH; Elliott, A; Elsayed, R; Emerson, MS; Emmanuel, YO; Emory, TH; Endale-Mangamba, LM; Enten, GA; Estefanía-Fernández, K; Estes, JD; Estrada-Mena, FJ; Evans, S; Ezra, L; Faria de, RO; Farraj, AK; Favre, C; Feng, B; Feng, J; Feng, L; Feng, W; Feng, X; Feng, Z; Fernandes, CLF; Fernández-Cuadros, ME; Fernie, AR; Ferrari, D; Florindo, PR; Fong, PC; Fontes, EPB; Fontinha, D; Fornari, VJ; Fox, NP; Fu, Q; Fujitaka, Y; Fukuhara, K; Fumeaux, T; Fuqua, C; Fustinoni, S; Gabbanelli, V; Gaikwad, S; Gall, ET; Galli, A; Gancedo, MA; Gandhi, MM; Gao, D; Gao, K; Gao, M; Gao, Q; Gao, X; Gao, Y; Gaponenko, V; Garber, A; Garcia, EM; García-Campos, C; García-Donas, J; García-Pérez, AL; Gasparri, F; Ge, C; Ge, D; Ge, JB; Ge, X; George, I; George, LA; Germani, G; Ghassemi Tabrizi, S; Gibon, Y; Gillent, E; Gillies, RS; Gilmour, MI; Goble, S; Goh, JC; Goiri, F; Goldfinger, LE; 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Immordino, P; Isla, MI; Jacquemond, V; Jacques, T; Jankowska, E; Jansen, JA; Jäntti, T; Jaque-Fernandez, F; Jarvis, GA; Jatt, LP; Jeon, JW; Jeong, SH; Jhunjhunwala, R; Ji, F; Jia, X; Jia, Y; Jian-Bo, Z; Jiang, GD; Jiang, L; Jiang, W; Jiang, WD; Jiang, Z; Jiménez-Hoyos, CA; Jin, S; Jobling, MG; John, CM; John, T; Johnson, CB; Jones, KI; Jones, WS; Joseph, OO; Ju, C; Judeinstein, P; Junges, A; Junnarkar, M; Jurkko, R; Kaleka, CC; Kamath, AV; Kang, X; Kantsadi, AL; Kapoor, M; Karim, Z; Kashuba, ADM; Kassa, E; Kasztura, M; Kataja, A; Katoh, T; Kaufman, JS; Kaupp, M; Kehinde, O; Kehrenberg, C; Kemper, N; Kerr, CW; Khan, AU; Khan, MF; Khan, ZUH; Khojasteh, SC; Kilburn, S; Kim, CG; Kim, DU; Kim, DY; Kim, HJ; Kim, J; Kim, OH; Kim, YH; King, C; Klein, A; Klingler, L; Knapp, AK; Ko, TK; Kodavanti, UP; Kolla, V; Kong, L; Kong, RY; Kong, X; Kore, S; Kortz, U; Korucu, B; Kovacs, A; Krahnert, I; Kraus, WE; Kuang, SY; Kuehn-Hajder, JE; Kurz, M; Kuśtrowski, P; Kwak, YD; Kyttaris, VC; Laga, SM; Laguerre, A; Laloo, A; Langaro, MC; Langham, MC; Lao, X; Larocca, MC; Lassus, J; Lattimer, TA; Lazar, S; Le, MH; Leal, DB; Leal, M; Leary, A; Ledermann, JA; Lee, JF; Lee, MV; Lee, NH; Leeds, CM; Leeds, JS; Lefrandt, JD; Leicht, AS; Leonard, M; Lev, S; Levy, K; Li, B; Li, C; Li, CM; Li, DH; Li, H; Li, J; Li, L; Li, LJ; Li, N; Li, P; Li, T; Li, X; Li, XH; Li, XQ; Li, XX; Li, Y; Li, Z; Li, ZY; Liao, YF; Lin, CC; Lin, MH; Lin, Y; Ling, Y; Links, TP; Lira-Romero, E; Liu, C; Liu, D; Liu, H; Liu, J; Liu, L; Liu, LP; Liu, M; Liu, T; Liu, W; Liu, X; Liu, XH; Liu, Y; Liuwantara, D; Ljumanovic, N; Lobo, L; Lokhande, K; Lopes, A; Lopes, RMRM; López-Gutiérrez, JC; López-Muñoz, MJ; López-Santamaría, M; Lorenzo, C; Lorusso, D; Losito, I; Lu, C; Lu, H; Lu, HZ; Lu, SH; Lu, SN; Lu, Y; Lu, ZY; Luboga, F; Luo, JJ; Luo, KL; Luo, Y; Lutomski, CA; Lv, W; M Piedade, MF; Ma, J; Ma, JQ; Ma, JX; Ma, N; Ma, P; Ma, S; Maciel, M; Madureira, M; Maganaris, C; Maginn, EJ; Mahnashi, MH; Maierhofer, M; Majetschak, M; Malla, TR; Maloney, L; Mann, DL; Mansuri, A; Marelli, E; Margulis, CJ; Marrella, A; Martin, BL; Martín-Francés, L; Martínez de Pinillos, M; Martínez-Navarro, EM; Martinez-Quintanilla Jimenez, D; Martínez-Velasco, A; Martínez-Villaseñor, L; Martinón-Torres, M; Martins, BA; Massongo, M; Mathew, AP; Mathews, D; Matsui, J; Matsumoto, KI; Mau, T; Maves, RC; Mayclin, SJ; Mayer, JM; Maynard, ND; Mayr, T; Mboowa, MG; McEvoy, MP; McIntyre, RC; McKay, JA; McPhail, MJW; McVeigh, AL; Mebazaa, A; Medici, V; Medina, DN; Mehmood, T; Mei-Li, C; Melku, M; Meloncelli, S; Mendes, GC; Mendoza-Velásquez, C; Mercadante, R; Mercado, MI; Merenda, MEZ; Meunier, J; Mi, SL; Michels, M; Mijatovic, V; Mikhailov, V; Milheiro, SA; Miller, DC; Ming, F; Mitsuishi, M; Miyashita, T; Mo, J; Mo, S; Modesto-Mata, M; Moeller, S; Monte, A; Monteiro, L; Montomoli, J; Moore, EE; Moore, HB; Moore, PK; Mor, MK; Moratalla-López, N; Moratilla Lapeña, L; Moreira, R; Moreno, MA; Mörk, AC; Morton, M; Mosier, JM; Mou, LH; Mougharbel, AS; Muccillo-Baisch, AL; Muñoz-Serrano, AJ; Mustafa, B; Nair, GM; Nakanishi, I; Nakanjako, D; Naraparaju, K; Nawani, N; Neffati, R; Neil, EC; Neilipovitz, D; Neira-Borrajo, I; Nelson, MT; Nery, PB; Nese, M; Nguyen, F; Nguyen, MH; Niazy, AA; Nicolaï, J; Nogueira, F; Norbäck, D; Novaretti, JV; O'Donnell, T; O'Dowd, A; O'Malley, DM; Oaknin, A; Ogata, K; Ohkubo, K; Ojha, M; Olaleye, MT; Olawande, B; Olomo, EJ; Ong, EWY; Ono, A; Onwumere, J; Ortiz Bibriesca, DM; Ou, X; Oza, AM; Ozturk, K; Özütemiz, C; Palacio-Pastrana, C; Palaparthi, A; Palevsky, PM; Pan, K; Pantanetti, S; Papachristou, DJ; Pariani, A; Parikh, CR; Parissis, J; Paroul, N; Parry, S; Patel, N; Patel, SM; Patel, VC; Pawar, S; Pefura-Yone, EW; Peixoto Andrade, BCO; Pelepenko, LE; Peña-Lora, D; Peng, S; Pérez-Moro, OS; Perez-Ortiz, AC; Perry, LM; Peter, CM; Phillips, NJ; Phillips, P; Pia Tek, J; Piner, LW; Pinto, EA; Pinto, SN; Piyachaturawat, P; Poka-Mayap, V; Polledri, E; Poloni, TE; Ponessa, G; Poole, ST; Post, AK; Potter, TM; Pressly, BB; Prouty, MG; Prudêncio, M; Pulkki, K; Pupier, C; Qian, H; Qian, ZP; Qiu, Y; Qu, G; Rahimi, S; Rahman, AU; Ramadan, H; Ramanna, S; Ramirez, I; Randolph, GJ; Rasheed, A; Rault, J; Raviprakash, V; Reale, E; Redpath, C; Rema, V; Remucal, CK; Remy, D; Ren, T; Ribeiro, LB; Riboli, G; Richards, J; Rieger, V; Rieusset, J; Riva, A; Rivabella Maknis, T; Robbins, JL; Robinson, CV; Roche-Campo, F; Rodriguez, R; Rodríguez-de-Cía, J; Rollenhagen, JE; Rosen, EP; Rub, D; Rubin, N; Rubin, NT; Ruurda, JP; Saad, O; Sabell, T; Saber, SE; Sabet, M; Sadek, MM; Saejio, A; Salinas, RM; Saliu, IO; Sande, D; Sang, D; Sangenito, LS; Santos, ALSD; Sarmiento Caldas, MC; Sassaroli, S; Sassi, V; Sato, J; Sauaia, A; Saunders, K; Saunders, PR; Savarino, SJ; Scambia, G; Scanlon, N; Schetinger, MR; Schinkel, AFL; Schladweiler, MC; Schofield, CJ; Schuepbach, RA; Schulz, J; Schwartz, N; Scorcella, C; Seeley, J; Seemann, F; Seinige, D; Sengoku, T; Seravalli, J; Sgromo, B; Shaheen, MY; Shan, L; Shanmugam, S; Shao, H; Sharma, S; Shaw, KJ; Shen, BQ; Shen, CH; Shen, P; Shen, S; Shen, Y; Shen, Z; Shi, J; Shi-Li, L; Shimoda, K; Shoji, Y; Shun, C; Silva, MA; Silva-Cardoso, J; Simas, NK; Simirgiotis, MJ; Sincock, SA; Singh, MP; Sionis, A; Siu, J; Sivieri, EM; Sjerps, MJ; Skoczen, SL; Slabon, A; Slette, IJ; Smith, MD; Smith, S; Smith, TG; Snapp, KS; Snow, SJ; Soares, MCF; Soberman, D; Solares, MD; Soliman, I; Song, J; Sorooshian, A; Sorrell, TC; Spinar, J; Staudt, A; Steinhart, C; Stern, ST; Stevens, DM; Stiers, KM; Stimming, U; Su, YG; Subbian, V; Suga, H; Sukhija-Cohen, A; Suksamrarn, A; Suksen, K; Sun, J; Sun, M; Sun, P; Sun, W; Sun, XF; Sun, Y; Sundell, J; Susan, LF; Sutjarit, N; Swamy, KV; Swisher, EM; Sykes, C; Takahashi, JA; Talmor, DS; Tan, B; Tan, ZK; Tang, L; Tang, S; Tanner, JJ; Tanwar, M; Tarazi, Z; Tarvasmäki, T; Tay, FR; Teketel, A; Temitayo, GI; Thersleff, T; Thiessen Philbrook, H; Thompson, LC; Thongon, N; Tian, B; Tian, F; Tian, Q; Timothy, AT; Tingle, MD; Titze, IR; Tolppanen, H; Tong, W; Toyoda, H; Tronconi, L; Tseng, CH; Tu, H; Tu, YJ; Tung, SY; Turpault, S; Tuynman, JB; Uemoto, AT; Ugurlu, M; Ullah, S; Underwood, RS; Ungell, AL; Usandizaga-Elio, I; Vakonakis, I; van Boxel, GI; van den Beucken, JJJP; van der Boom, T; van Slegtenhorst, MA; Vanni, JR; Vaquera, A; Vasconcellos, RS; Velayos, M; Vena, R; Ventura, G; Verso, MG; Vincent, RP; Vitale, F; Vitali, S; Vlek, SL; Vleugels, MPH; Volkmann, N; Vukelic, M; Wagner Mackenzie, B; Wairagala, P; Waller, SB; Wan, J; Wan, MT; Wan, Y; Wang, CC; Wang, H; Wang, J; Wang, JF; Wang, K; Wang, L; Wang, M; Wang, S; Wang, WM; Wang, X; Wang, Y; Wang, YD; Wang, YF; Wang, Z; Wang, ZG; Warriner, K; Weberpals, JI; Weerachayaphorn, J; Wehrli, FW; Wei, J; Wei, KL; Weinheimer, CJ; Weisbord, SD; Wen, S; Wendel Garcia, PD; Williams, JW; Williams, R; Winkler, C; Wirman, AP; Wong, S; Woods, CM; Wu, B; Wu, C; Wu, F; Wu, P; Wu, S; Wu, Y; Wu, YN; Wu, ZH; Wurtzel, JGT; Xia, L; Xia, Z; Xia, ZZ; Xiao, H; Xie, C; Xin, ZM; Xing, Y; Xing, Z; Xu, S; Xu, SB; Xu, T; Xu, X; Xu, Y; Xue, L; Xun, J; Yaffe, MB; Yalew, A; Yamamoto, S; Yan, D; Yan, H; Yan, S; Yan, X; Yang, AD; Yang, E; Yang, H; Yang, J; Yang, JL; Yang, K; Yang, M; Yang, P; Yang, Q; Yang, S; Yang, W; Yang, X; Yang, Y; Yao, JC; Yao, WL; Yao, Y; Yaqub, TB; Ye, J; Ye, W; Yen, CW; Yeter, HH; Yin, C; Yip, V; Yong-Yi, J; Yu, HJ; Yu, MF; Yu, S; Yu, W; Yu, WW; Yu, X; Yuan, P; Yuan, Q; Yue, XY; Zaia, AA; Zakhary, SY; Zalwango, F; Zamalloa, A; Zamparo, P; Zampini, IC; Zani, JL; Zeitoun, R; Zeng, N; Zenteno, JC; Zepeda-Palacio, C; Zhai, C; Zhang, B; Zhang, G; Zhang, J; Zhang, K; Zhang, Q; Zhang, R; Zhang, T; Zhang, X; Zhang, Y; Zhang, YY; Zhao, B; Zhao, D; Zhao, G; Zhao, H; Zhao, Q; Zhao, R; Zhao, S; Zhao, T; Zhao, X; Zhao, XA; Zhao, Y; Zhao, Z; Zheng, Z; Zhi-Min, G; Zhou, CL; Zhou, HD; Zhou, J; Zhou, W; Zhou, XQ; Zhou, Z; Zhu, C; Zhu, H; Zhu, L; Zhu, Y; Zitzmann, N; Zou, L; Zou, Y, 2022)	0.72
" This paper provides a review of the pharmacokinetics (PK) of the IV tramadol dosing regimen being developed in the United States, its abuse potential as documented in the literature, and its safety record in clinical practice, and discusses how IV tramadol may become a useful option for patients in the United States with acute pain."	( IV tramadol: A novel option for US patients with acute pain-A review of its pharmacokinetics, abuse potential and clinical safety record. Harnett, M; Lu, L; Reines, SA, )	0.99
" The total postoperative dosage of tramadol hydrochloride, length of hospitalization, quality of life (QoL), and inflammation levels were recorded."	( Ultrasound-Guided Thoracic Paravertebral Nerve Block on Postoperative Pain, Quality of Life, and Recovery in Patients with Non-Small-Cell Lung Cancer. Wang, J; Xie, S; Zheng, C, 2021)	0.9
"In the design of abuse-deterrent formulations (ADFs), pharmaceutical strategies that do not modify the physical and chemical properties of opioid dosage forms should be investigated."	( Evaluation of the impact of abuse deterring agents on the physicochemical factors of tramadol-loaded tablet and the definition of new abuse deterrent index. Jin, G; Lee, BJ; Ngo, HV; Park, C; Park, G; Won, DG, 2021)	0.85
"0001) altered glutathione and malondialdehyde levels in the fetuses, pregnant, and nonpregnant animals (tissue homogenates) at all dosage levels were indicative of tramadol induced oxidative stress."	( Maternotoxicity and fetotoxicity in Rattus norvegicus albinus exposed to tramadol during the late phase of pregnancy. Abdel-Daim, MM; Akhtar, MF; Baig, MMFA; Rasul, A; Saleem, A; Saleem, M; Sharif, A; Younas, S, 2021)	1.05
" Tramadol is dosed at 1-1."	( HPLC-UV assay of tramadol and O-desmethyltramadol in human plasma containing other drugs potentially co-administered to participants in a paediatric population pharmacokinetic study. Hua, AJ; Lim, LY; Nguyen, MN; Salman, S; Tang, EKY; von Ungern Sternberg, BS; Yoo, O, 2021)	1.87
" We performed a dose-response analysis using the average daily dose."	( Association between tramadol use and seizures: A nationwide case-case-time-control study. Jeon, HL; Kim, JH; Lee, H; Park, S; Shin, JY, 2022)	1.04
"Strict adherence to pharmacological dosage regimens is a prerequisite to the success of most treatments, particularly for patients in drug abuse programs."	( Urinalysis based assessment of compliance and drug use patterns in patients prescribed tramadol: A cross-sectional study from a tertiary care centre. Ghosh, S; Jain, R; Saifi, N; Sarkar, S, 2022)	0.94
"To compare the effect of intermittent tramadol dosing vs tramadol administration via patient-controlled pump on pain after lumbar discectomy."	( Intermittent tramadol vs tramadol administration via patient-controlled pump after lumbar discectomy: a randomized controlled trial. Friganović, A; Kurtović, B; Milošević, M; Rotim, C; Rotim, K; Sajko, T, 2022)	1.36
"To develop and assess new dosage forms for the alternative to existing oral medication for peripheral neuropathy, a hydrogel film in the skin patch formation containing tramadol hydrochloride (TRA), a water-soluble drug used as an analgesic, was prepared and evaluated."	( Preparation and Evaluation of Hydrogel Film Containing Tramadol for Reduction of Peripheral Neuropathic Pain. Hanawa, T; Hiroki, A; Kawano, Y; Miyajima, A; Natori, N; Shibano, Y; Taguchi, M; Yoshizawa, K, 2023)	1.35
" The developed method was successfully applied to determine tramadol and paracetamol in various dosage forms and in urine biological samples."	( Capillary zone electrophoresis in combination with UV detection for simultaneous determination of tramadol and paracetamol in pharmaceutical and biological samples. Čižmárová, I; Horniaková, A; Matušková, M; Mikuš, P; Piešťanský, J; Štefánik, O, 2022)	1.18
" These should be used in reduced doses, avoiding tizanidine with liver disease and reducing baclofen dosing with kidney disease."	( Pharmacotherapy for Spine-Related Pain in Older Adults. Fu, JL; Perloff, MD, 2022)	0.72
" 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
" The sufentanil 5 µg/kg dosage in the PCA regimen is superior to sufentanil 4 µg/kg alone or combined with tramadol in lowering moderate to severe pain."	( Effectiveness of Sufentanil-Based Patient-Controlled Analgesia Regimen in Children and Incidence of Adverse Events Following Major Congenital Structure Repairs. Liu, F; Xie, D; Zuo, Y, 2023)	1.12
" The proposed spectrophotometric techniques could be applied for the routine analysis and quality control of the studied drugs in their dosage form."	( Eco-friendly simultaneous multi-spectrophotometric estimation of the newly approved drug combination of celecoxib and tramadol hydrochloride tablets in its dosage form. Belal, F; Hadad, GM; Ramadan, HS; Salam, RAA; Salim, MM, 2023)	1.12

Role	Description
delta-opioid receptor agonist	null
kappa-opioid receptor agonist	A compound that exhibits agonist activity at the kappa-opioid receptor.
mu-opioid receptor agonist	A compound that exhibits agonist activity at the mu-opioid receptor.
adrenergic uptake inhibitor	Adrenergic uptake inhibitors are drugs that block the transport of adrenergic transmitters into axon terminals or into storage vesicles within terminals. The tricyclic antidepressants and amphetamines are among the therapeutically important drugs that may act via inhibition of adrenergic transport. Many of these drugs also block transport of serotonin.
antitussive	An agent that suppresses cough. Antitussives have a central or a peripheral action on the cough reflex, or a combination of both. Compare with expectorants, which are considered to increase the volume of secretions in the respiratory tract, so facilitating their removal by ciliary action and coughing, and mucolytics, which decrease the viscosity of mucus, facilitating its removal by ciliary action and expectoration.
capsaicin receptor antagonist	Any substance which blocks the painful sensation of heat caused by capsaicin acting on the TRPV1 ion channel.
muscarinic antagonist	A drug that binds to but does not activate muscarinic cholinergic receptors, thereby blocking the actions of endogenous acetylcholine or exogenous agonists.
nicotinic antagonist	An antagonist at the nicotinic cholinergic receptor.
NMDA receptor antagonist	Any substance that inhibits the action of N-methyl-D-aspartate (NMDA) receptors. They tend to induce a state known as dissociative anesthesia, marked by catalepsy, amnesia, and analgesia, while side effects can include hallucinations, nightmares, and confusion. Due to their psychotomimetic effects, many NMDA receptor antagonists are used as recreational drugs.
opioid analgesic	A narcotic or opioid substance, synthetic or semisynthetic agent producing profound analgesia, drowsiness, and changes in mood.
serotonergic antagonist	Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or serotonergic agonists.
serotonin uptake inhibitor	A compound that specifically inhibits the reuptake of serotonin in the brain. This increases the serotonin concentration in the synaptic cleft which then activates serotonin receptors to a greater extent.
metabolite	Any intermediate or product resulting from metabolism. The term 'metabolite' subsumes the classes commonly known as primary and secondary metabolites.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Class	Description
2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol	A tertiary alcohol that is cyclohexanol substituted at positions 1 and 2 by 3-methoxyphenyl and dimethylaminomethyl groups respectively.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Pathway	Proteins	Compounds
Tramadol Metabolism Pathway	7	17
Tramadol Action Action Pathway	31	11

Protein	Taxonomy	Measurement	Average (µ)	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
glp-1 receptor, partial	Homo sapiens (human)	Potency	6.3096	0.0184	6.8060	14.1254	AID624172
TDP1 protein	Homo sapiens (human)	Potency	2.9093	0.0008	11.3822	44.6684	AID686979
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Protein	Taxonomy	Measurement	Average	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
Solute carrier family 22 member 1	Homo sapiens (human)	IC50 (µMol)	88.7600	0.2100	5.5537	10.0000	AID1526751
Mu-type opioid receptor	Homo sapiens (human)	Ki	2.4000	0.0000	0.4197	10.0000	AID1303084
Delta-type opioid receptor	Homo sapiens (human)	Ki	10.0000	0.0000	0.5978	9.9300	AID1303075
Kappa-type opioid receptor	Homo sapiens (human)	Ki	10.0000	0.0000	0.3624	10.0000	AID1303077
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Protein	Taxonomy	Measurement	Average	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
Mu-type opioid receptor	Homo sapiens (human)	EC50 (µMol)	1.0000	0.0000	0.3263	9.4000	AID1303079
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Process	via Protein(s)	Taxonomy
xenobiotic metabolic process	Solute carrier family 22 member 1	Homo sapiens (human)
neurotransmitter transport	Solute carrier family 22 member 1	Homo sapiens (human)
serotonin transport	Solute carrier family 22 member 1	Homo sapiens (human)
establishment or maintenance of transmembrane electrochemical gradient	Solute carrier family 22 member 1	Homo sapiens (human)
organic cation transport	Solute carrier family 22 member 1	Homo sapiens (human)
quaternary ammonium group transport	Solute carrier family 22 member 1	Homo sapiens (human)
prostaglandin transport	Solute carrier family 22 member 1	Homo sapiens (human)
monoamine transport	Solute carrier family 22 member 1	Homo sapiens (human)
putrescine transport	Solute carrier family 22 member 1	Homo sapiens (human)
spermidine transport	Solute carrier family 22 member 1	Homo sapiens (human)
acetylcholine transport	Solute carrier family 22 member 1	Homo sapiens (human)
dopamine transport	Solute carrier family 22 member 1	Homo sapiens (human)
norepinephrine transport	Solute carrier family 22 member 1	Homo sapiens (human)
thiamine transport	Solute carrier family 22 member 1	Homo sapiens (human)
xenobiotic transport	Solute carrier family 22 member 1	Homo sapiens (human)
epinephrine transport	Solute carrier family 22 member 1	Homo sapiens (human)
serotonin uptake	Solute carrier family 22 member 1	Homo sapiens (human)
norepinephrine uptake	Solute carrier family 22 member 1	Homo sapiens (human)
thiamine transmembrane transport	Solute carrier family 22 member 1	Homo sapiens (human)
metanephric proximal tubule development	Solute carrier family 22 member 1	Homo sapiens (human)
purine-containing compound transmembrane transport	Solute carrier family 22 member 1	Homo sapiens (human)
dopamine uptake	Solute carrier family 22 member 1	Homo sapiens (human)
monoatomic cation transmembrane transport	Solute carrier family 22 member 1	Homo sapiens (human)
transport across blood-brain barrier	Solute carrier family 22 member 1	Homo sapiens (human)
(R)-carnitine transmembrane transport	Solute carrier family 22 member 1	Homo sapiens (human)
acyl carnitine transmembrane transport	Solute carrier family 22 member 1	Homo sapiens (human)
spermidine transmembrane transport	Solute carrier family 22 member 1	Homo sapiens (human)
cellular detoxification	Solute carrier family 22 member 1	Homo sapiens (human)
xenobiotic transport across blood-brain barrier	Solute carrier family 22 member 1	Homo sapiens (human)
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	Mu-type opioid receptor	Homo sapiens (human)
adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway	Mu-type opioid receptor	Homo sapiens (human)
phospholipase C-activating G protein-coupled receptor signaling pathway	Mu-type opioid receptor	Homo sapiens (human)
sensory perception	Mu-type opioid receptor	Homo sapiens (human)
negative regulation of cell population proliferation	Mu-type opioid receptor	Homo sapiens (human)
sensory perception of pain	Mu-type opioid receptor	Homo sapiens (human)
G protein-coupled opioid receptor signaling pathway	Mu-type opioid receptor	Homo sapiens (human)
behavioral response to ethanol	Mu-type opioid receptor	Homo sapiens (human)
positive regulation of neurogenesis	Mu-type opioid receptor	Homo sapiens (human)
negative regulation of Wnt protein secretion	Mu-type opioid receptor	Homo sapiens (human)
positive regulation of ERK1 and ERK2 cascade	Mu-type opioid receptor	Homo sapiens (human)
calcium ion transmembrane transport	Mu-type opioid receptor	Homo sapiens (human)
cellular response to morphine	Mu-type opioid receptor	Homo sapiens (human)
regulation of cellular response to stress	Mu-type opioid receptor	Homo sapiens (human)
regulation of NMDA receptor activity	Mu-type opioid receptor	Homo sapiens (human)
neuropeptide signaling pathway	Mu-type opioid receptor	Homo sapiens (human)
immune response	Delta-type opioid receptor	Homo sapiens (human)
G protein-coupled receptor signaling pathway	Delta-type opioid receptor	Homo sapiens (human)
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	Delta-type opioid receptor	Homo sapiens (human)
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	Delta-type opioid receptor	Homo sapiens (human)
phospholipase C-activating G protein-coupled receptor signaling pathway	Delta-type opioid receptor	Homo sapiens (human)
adult locomotory behavior	Delta-type opioid receptor	Homo sapiens (human)
negative regulation of gene expression	Delta-type opioid receptor	Homo sapiens (human)
negative regulation of protein-containing complex assembly	Delta-type opioid receptor	Homo sapiens (human)
positive regulation of CREB transcription factor activity	Delta-type opioid receptor	Homo sapiens (human)
positive regulation of peptidyl-serine phosphorylation	Delta-type opioid receptor	Homo sapiens (human)
response to nicotine	Delta-type opioid receptor	Homo sapiens (human)
G protein-coupled opioid receptor signaling pathway	Delta-type opioid receptor	Homo sapiens (human)
eating behavior	Delta-type opioid receptor	Homo sapiens (human)
regulation of mitochondrial membrane potential	Delta-type opioid receptor	Homo sapiens (human)
regulation of calcium ion transport	Delta-type opioid receptor	Homo sapiens (human)
cellular response to growth factor stimulus	Delta-type opioid receptor	Homo sapiens (human)
cellular response to hypoxia	Delta-type opioid receptor	Homo sapiens (human)
cellular response to toxic substance	Delta-type opioid receptor	Homo sapiens (human)
neuropeptide signaling pathway	Delta-type opioid receptor	Homo sapiens (human)
immune response	Kappa-type opioid receptor	Homo sapiens (human)
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	Kappa-type opioid receptor	Homo sapiens (human)
phospholipase C-activating G protein-coupled receptor signaling pathway	Kappa-type opioid receptor	Homo sapiens (human)
chemical synaptic transmission	Kappa-type opioid receptor	Homo sapiens (human)
sensory perception	Kappa-type opioid receptor	Homo sapiens (human)
locomotory behavior	Kappa-type opioid receptor	Homo sapiens (human)
sensory perception of pain	Kappa-type opioid receptor	Homo sapiens (human)
adenylate cyclase-inhibiting opioid receptor signaling pathway	Kappa-type opioid receptor	Homo sapiens (human)
response to insulin	Kappa-type opioid receptor	Homo sapiens (human)
positive regulation of dopamine secretion	Kappa-type opioid receptor	Homo sapiens (human)
negative regulation of luteinizing hormone secretion	Kappa-type opioid receptor	Homo sapiens (human)
response to nicotine	Kappa-type opioid receptor	Homo sapiens (human)
G protein-coupled opioid receptor signaling pathway	Kappa-type opioid receptor	Homo sapiens (human)
maternal behavior	Kappa-type opioid receptor	Homo sapiens (human)
eating behavior	Kappa-type opioid receptor	Homo sapiens (human)
response to estrogen	Kappa-type opioid receptor	Homo sapiens (human)
estrous cycle	Kappa-type opioid receptor	Homo sapiens (human)
response to ethanol	Kappa-type opioid receptor	Homo sapiens (human)
regulation of saliva secretion	Kappa-type opioid receptor	Homo sapiens (human)
behavioral response to cocaine	Kappa-type opioid receptor	Homo sapiens (human)
sensory perception of temperature stimulus	Kappa-type opioid receptor	Homo sapiens (human)
defense response to virus	Kappa-type opioid receptor	Homo sapiens (human)
cellular response to lipopolysaccharide	Kappa-type opioid receptor	Homo sapiens (human)
cellular response to glucose stimulus	Kappa-type opioid receptor	Homo sapiens (human)
positive regulation of p38MAPK cascade	Kappa-type opioid receptor	Homo sapiens (human)
positive regulation of potassium ion transmembrane transport	Kappa-type opioid receptor	Homo sapiens (human)
response to acrylamide	Kappa-type opioid receptor	Homo sapiens (human)
positive regulation of eating behavior	Kappa-type opioid receptor	Homo sapiens (human)
conditioned place preference	Kappa-type opioid receptor	Homo sapiens (human)
neuropeptide signaling pathway	Kappa-type opioid receptor	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Process	via Protein(s)	Taxonomy
acetylcholine transmembrane transporter activity	Solute carrier family 22 member 1	Homo sapiens (human)
neurotransmitter transmembrane transporter activity	Solute carrier family 22 member 1	Homo sapiens (human)
dopamine:sodium symporter activity	Solute carrier family 22 member 1	Homo sapiens (human)
norepinephrine:sodium symporter activity	Solute carrier family 22 member 1	Homo sapiens (human)
protein binding	Solute carrier family 22 member 1	Homo sapiens (human)
monoamine transmembrane transporter activity	Solute carrier family 22 member 1	Homo sapiens (human)
secondary active organic cation transmembrane transporter activity	Solute carrier family 22 member 1	Homo sapiens (human)
organic anion transmembrane transporter activity	Solute carrier family 22 member 1	Homo sapiens (human)
organic cation transmembrane transporter activity	Solute carrier family 22 member 1	Homo sapiens (human)
prostaglandin transmembrane transporter activity	Solute carrier family 22 member 1	Homo sapiens (human)
pyrimidine nucleoside transmembrane transporter activity	Solute carrier family 22 member 1	Homo sapiens (human)
thiamine transmembrane transporter activity	Solute carrier family 22 member 1	Homo sapiens (human)
putrescine transmembrane transporter activity	Solute carrier family 22 member 1	Homo sapiens (human)
spermidine transmembrane transporter activity	Solute carrier family 22 member 1	Homo sapiens (human)
quaternary ammonium group transmembrane transporter activity	Solute carrier family 22 member 1	Homo sapiens (human)
toxin transmembrane transporter activity	Solute carrier family 22 member 1	Homo sapiens (human)
identical protein binding	Solute carrier family 22 member 1	Homo sapiens (human)
xenobiotic transmembrane transporter activity	Solute carrier family 22 member 1	Homo sapiens (human)
(R)-carnitine transmembrane transporter activity	Solute carrier family 22 member 1	Homo sapiens (human)
G-protein alpha-subunit binding	Mu-type opioid receptor	Homo sapiens (human)
G protein-coupled receptor activity	Mu-type opioid receptor	Homo sapiens (human)
beta-endorphin receptor activity	Mu-type opioid receptor	Homo sapiens (human)
voltage-gated calcium channel activity	Mu-type opioid receptor	Homo sapiens (human)
protein binding	Mu-type opioid receptor	Homo sapiens (human)
morphine receptor activity	Mu-type opioid receptor	Homo sapiens (human)
G-protein beta-subunit binding	Mu-type opioid receptor	Homo sapiens (human)
neuropeptide binding	Mu-type opioid receptor	Homo sapiens (human)
G protein-coupled opioid receptor activity	Delta-type opioid receptor	Homo sapiens (human)
protein binding	Delta-type opioid receptor	Homo sapiens (human)
receptor serine/threonine kinase binding	Delta-type opioid receptor	Homo sapiens (human)
G protein-coupled enkephalin receptor activity	Delta-type opioid receptor	Homo sapiens (human)
neuropeptide binding	Delta-type opioid receptor	Homo sapiens (human)
G protein-coupled opioid receptor activity	Kappa-type opioid receptor	Homo sapiens (human)
protein binding	Kappa-type opioid receptor	Homo sapiens (human)
receptor serine/threonine kinase binding	Kappa-type opioid receptor	Homo sapiens (human)
dynorphin receptor activity	Kappa-type opioid receptor	Homo sapiens (human)
neuropeptide binding	Kappa-type opioid receptor	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Process	via Protein(s)	Taxonomy
plasma membrane	Solute carrier family 22 member 1	Homo sapiens (human)
basal plasma membrane	Solute carrier family 22 member 1	Homo sapiens (human)
membrane	Solute carrier family 22 member 1	Homo sapiens (human)
basolateral plasma membrane	Solute carrier family 22 member 1	Homo sapiens (human)
apical plasma membrane	Solute carrier family 22 member 1	Homo sapiens (human)
lateral plasma membrane	Solute carrier family 22 member 1	Homo sapiens (human)
presynapse	Solute carrier family 22 member 1	Homo sapiens (human)
endosome	Mu-type opioid receptor	Homo sapiens (human)
endoplasmic reticulum	Mu-type opioid receptor	Homo sapiens (human)
Golgi apparatus	Mu-type opioid receptor	Homo sapiens (human)
plasma membrane	Mu-type opioid receptor	Homo sapiens (human)
axon	Mu-type opioid receptor	Homo sapiens (human)
dendrite	Mu-type opioid receptor	Homo sapiens (human)
perikaryon	Mu-type opioid receptor	Homo sapiens (human)
synapse	Mu-type opioid receptor	Homo sapiens (human)
plasma membrane	Mu-type opioid receptor	Homo sapiens (human)
neuron projection	Mu-type opioid receptor	Homo sapiens (human)
plasma membrane	Delta-type opioid receptor	Homo sapiens (human)
synaptic vesicle membrane	Delta-type opioid receptor	Homo sapiens (human)
dendrite membrane	Delta-type opioid receptor	Homo sapiens (human)
presynaptic membrane	Delta-type opioid receptor	Homo sapiens (human)
axon terminus	Delta-type opioid receptor	Homo sapiens (human)
spine apparatus	Delta-type opioid receptor	Homo sapiens (human)
postsynaptic density membrane	Delta-type opioid receptor	Homo sapiens (human)
neuronal dense core vesicle	Delta-type opioid receptor	Homo sapiens (human)
plasma membrane	Delta-type opioid receptor	Homo sapiens (human)
neuron projection	Delta-type opioid receptor	Homo sapiens (human)
nucleoplasm	Kappa-type opioid receptor	Homo sapiens (human)
mitochondrion	Kappa-type opioid receptor	Homo sapiens (human)
cytosol	Kappa-type opioid receptor	Homo sapiens (human)
plasma membrane	Kappa-type opioid receptor	Homo sapiens (human)
membrane	Kappa-type opioid receptor	Homo sapiens (human)
sarcoplasmic reticulum	Kappa-type opioid receptor	Homo sapiens (human)
T-tubule	Kappa-type opioid receptor	Homo sapiens (human)
dendrite	Kappa-type opioid receptor	Homo sapiens (human)
synaptic vesicle membrane	Kappa-type opioid receptor	Homo sapiens (human)
presynaptic membrane	Kappa-type opioid receptor	Homo sapiens (human)
perikaryon	Kappa-type opioid receptor	Homo sapiens (human)
axon terminus	Kappa-type opioid receptor	Homo sapiens (human)
postsynaptic membrane	Kappa-type opioid receptor	Homo sapiens (human)
plasma membrane	Kappa-type opioid receptor	Homo sapiens (human)
neuron projection	Kappa-type opioid receptor	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Assay ID	Title	Year	Journal	Article
AID504749	qHTS profiling for inhibitors of Plasmodium falciparum proliferation	2011	Science (New York, N.Y.), Aug-05, Volume: 333, Issue:6043	Chemical genomic profiling for antimalarial therapies, response signatures, and molecular targets.
AID651635	Viability Counterscreen for Primary qHTS for Inhibitors of ATXN expression
AID588497	High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set	2010	Current protocols in cytometry, Oct, Volume: Chapter 13	Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588497	High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set	2006	Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5	Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588497	High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set	2010	Assay and drug development technologies, Feb, Volume: 8, Issue:1	High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID588499	High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set	2010	Current protocols in cytometry, Oct, Volume: Chapter 13	Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588499	High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set	2006	Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5	Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588499	High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set	2010	Assay and drug development technologies, Feb, Volume: 8, Issue:1	High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID588501	High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set	2010	Current protocols in cytometry, Oct, Volume: Chapter 13	Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588501	High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set	2006	Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5	Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588501	High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set	2010	Assay and drug development technologies, Feb, Volume: 8, Issue:1	High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID504810	Antagonists of the Thyroid Stimulating Hormone Receptor: HTS campaign	2010	Endocrinology, Jul, Volume: 151, Issue:7	A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID504812	Inverse Agonists of the Thyroid Stimulating Hormone Receptor: HTS campaign	2010	Endocrinology, Jul, Volume: 151, Issue:7	A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID1745845	Primary qHTS for Inhibitors of ATXN expression
AID1689586	Displacement of [3H]-DAMGO from rat mu opioid receptor expressed in CHO cells at 1 uM incubated for 30 mins by liquid scintillation counting method relative to control	2020	European journal of medicinal chemistry, Mar-01, Volume: 189	Discovery of 3-((dimethylamino)methyl)-4-hydroxy-4-(3-methoxyphenyl)-N-phenylpiperidine-1-carboxamide as novel potent analgesic.
AID1573872	Antihyperalgesic activity in Sprague-Dawley rat model of cisplatin-induced peripheral neuropathy assessed as increase in paw withdrawal latency at 40 mg/kg, po administered once daily via gavage for 7 days measured 4 hrs post last dose by plantar test	2019	Bioorganic & medicinal chemistry letters, 01-15, Volume: 29, Issue:2	Discovery and evaluation of novel FAAH inhibitors in neuropathic pain model.
AID1526752	Passive membrane permeability by LC-MS/MS analysis based PAMPA	2019	Journal of medicinal chemistry, 11-14, Volume: 62, Issue:21	Opioids as Substrates and Inhibitors of the Genetically Highly Variable Organic Cation Transporter OCT1.
AID1303084	Displacement of [3H]naloxone from human MOR expressed in CHO-K1 cell membranes after 60 mins by microbeta scintillation counting method	2016	ACS medicinal chemistry letters, Apr-14, Volume: 7, Issue:4	Discovery of Potent and Selective Agonists of δ Opioid Receptor by Revisiting the "Message-Address" Concept.
AID1303079	Agonist activity at human MOR expressed in CHO cell membranes after 60 mins by [35S]GTP-gamma-S binding assay	2016	ACS medicinal chemistry letters, Apr-14, Volume: 7, Issue:4	Discovery of Potent and Selective Agonists of δ Opioid Receptor by Revisiting the "Message-Address" Concept.
AID1689587	Displacement of [3H]-DPDPE from rat delta opioid receptor expressed in CHO cells at 1 uM incubated for 30 mins by liquid scintillation counting method relative to control	2020	European journal of medicinal chemistry, Mar-01, Volume: 189	Discovery of 3-((dimethylamino)methyl)-4-hydroxy-4-(3-methoxyphenyl)-N-phenylpiperidine-1-carboxamide as novel potent analgesic.
AID1689592	Antinociceptive activity in Kunming mouse assessed as maximum possible effect by measuring latency threshold at 50 mg/kg, ip by hot plate test relative to control	2020	European journal of medicinal chemistry, Mar-01, Volume: 189	Discovery of 3-((dimethylamino)methyl)-4-hydroxy-4-(3-methoxyphenyl)-N-phenylpiperidine-1-carboxamide as novel potent analgesic.
AID1689588	Displacement of [3H]-U69593 from human kappa opioid receptor expressed in CHO cells at 1 uM incubated for 30 mins by liquid scintillation counting method relative to control	2020	European journal of medicinal chemistry, Mar-01, Volume: 189	Discovery of 3-((dimethylamino)methyl)-4-hydroxy-4-(3-methoxyphenyl)-N-phenylpiperidine-1-carboxamide as novel potent analgesic.
AID1303074	Displacement of [3H]DAMGO from human MOR expressed in CHO cell membranes at 1 uM after 60 mins	2016	ACS medicinal chemistry letters, Apr-14, Volume: 7, Issue:4	Discovery of Potent and Selective Agonists of δ Opioid Receptor by Revisiting the "Message-Address" Concept.
AID1526751	Inhibition of human OCT1 expressed in HEK293 cells assessed as reduction in ASP+ substrate uptake by microplate reader based analysis	2019	Journal of medicinal chemistry, 11-14, Volume: 62, Issue:21	Opioids as Substrates and Inhibitors of the Genetically Highly Variable Organic Cation Transporter OCT1.
AID1303075	Displacement of [3H]DPDPE from human DOR expressed in CHO cell membranes after 60 mins	2016	ACS medicinal chemistry letters, Apr-14, Volume: 7, Issue:4	Discovery of Potent and Selective Agonists of δ Opioid Receptor by Revisiting the "Message-Address" Concept.
AID1303077	Displacement of [3H]U69593 from human KOR expressed in CHO cell membranes after 60 mins	2016	ACS medicinal chemistry letters, Apr-14, Volume: 7, Issue:4	Discovery of Potent and Selective Agonists of δ Opioid Receptor by Revisiting the "Message-Address" Concept.
AID1159607	Screen for inhibitors of RMI FANCM (MM2) intereaction	2016	Journal of biomolecular screening, Jul, Volume: 21, Issue:6	A High-Throughput Screening Strategy to Identify Protein-Protein Interaction Inhibitors That Block the Fanconi Anemia DNA Repair Pathway.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Timeframe	Studies, This Drug (%)	All Drugs %
pre-1990	68 (1.99)	18.7374
1990's	309 (9.06)	18.2507
2000's	1033 (30.29)	29.6817
2010's	1422 (41.70)	24.3611
2020's	578 (16.95)	2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Publication Type	This drug (%)	All Drugs (%)
Trials	1,151 (30.92%)	5.53%
Reviews	330 (8.86%)	6.00%
Case Studies	350 (9.40%)	4.05%
Observational	46 (1.24%)	0.25%
Other	1,846 (49.58%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (302)

Trial Overview

Trial	Phase	Enrollment	Study Type	Start Date	Status
The Efficiency of DYPIRON and TRAMADOL in Addition to Local Anesthesia Prior to Incision and Drainage Procedure in Peritonsillar Abscess [NCT01227200]		32 participants (Anticipated)	Interventional	2011-11-30	Not yet recruiting
Comparative Study Between Intraperitoneal Administration of Either Bupivacaine and Tramadol Versus Bupivacaine and Dexmedetomedine for Analgesia After Abdominal Laparoscopic Cancer Surgeries. A Prospective Randomized Pilot Study [NCT04813016]	Phase 2/Phase 3	100 participants (Actual)	Interventional	2021-03-01	Completed
Oral Naproxen Versus Oral Tramadol for Analgesia After Cesarean Delivery - A Randomized Controlled Trial [NCT01165814]		120 participants (Actual)	Interventional	2006-08-31	Completed
A Phase 3, Multicenter, Randomized, Double-Blind, Three-Arm Study to Evaluate the Efficacy and Safety of Tramadol Infusion (AVE-901) Versus Placebo and Morphine in the Management of Postoperative Pain Following Abdominoplasty [NCT03774836]	Phase 3	360 participants (Anticipated)	Interventional	2018-12-14	Active, not recruiting
Single Site Pharmacokinetic Non-interaction Study With Open-label, Randomized, Single-dose, Three-period, Six-sequence, Crossover Design to Compare Tramadol Hydrochloride 25 mg Capsules (Tradol [Trade Mark], Product of Grünenthal Mexico S.A. de C.V.) and [NCT03767036]	Phase 1	30 participants (Actual)	Interventional	2017-06-05	Completed
A Randomized, Double-blind, Multi-site, Comparator-controlled, Phase III Trial to Evaluate the Efficacy and Safety of a Fixed-dose Combination of Tramadol Hydrochloride and Diclofenac Sodium in Acute Moderate to Severe Pain After Third Molar Extraction [NCT03714672]	Phase 3	1,151 participants (Actual)	Interventional	2017-08-26	Completed
Efficacy, Safety, Tolerability and Pharmacokinetics of Concomitant Administration of Tramadol With Duloxetine or Pregabalin: a Randomized Controlled Flexible-dose Study in Patients With Neuropathic Pain [NCT01116531]	Phase 4	0 participants (Actual)	Interventional	2010-04-30	Withdrawn
A Randomized Trial of the Analgesic Efficacy of Wound Infiltration With Tramadol After Cesarean Delivery Under General Anesthesia [NCT02518438]	Phase 4	60 participants (Actual)	Interventional	2012-05-31	Completed
Randomized, Prospective Study of the Assessment, Prevention and Management of Acute Post-herniotomy Pain [NCT01345162]	Phase 4	200 participants (Actual)	Interventional	2010-03-31	Completed
A Multi-center, Double-blinded, Randomized, Active-controlled, Parallel Design, phaseII Study to Investigate the Efficacy and Safety of YYC301 in Subject With Knee Osteoarthritis. [NCT03850587]	Phase 2	261 participants (Actual)	Interventional	2018-08-30	Completed
The Influence of Tramadol on Platelet Function [NCT05237492]	Phase 4	15 participants (Anticipated)	Interventional	2022-01-26	Recruiting
National, Multicenter, Randomized, Double-blind, Triple-dummy, Phase II Clinical Trial to Evaluate the Efficacy and Safety of Canadá Association in the Treatment of Chronic Pain [NCT05125978]	Phase 2	0 participants (Actual)	Interventional	2026-09-30	Withdrawn(stopped due to Strategy review)
National, Multicenter, Randomized, Double-blind, Triple-dummy, Phase II Clinical Trial to Evaluate the Efficacy and Safety of Tiradentes Association in the Treatment of Acute Pain [NCT04593329]	Phase 2	0 participants (Actual)	Interventional	2023-03-31	Withdrawn(stopped due to Strategy review)
Comparison Between the Effects of Intravenous Morphine, Tramadol and Ketorolac on Stress and Immune Responses in Patients Undergoing Modified Radical Mastectomy [NCT02449954]	Phase 2/Phase 3	60 participants (Actual)	Interventional	2014-06-30	Active, not recruiting
The Effect of Intrauterine Lidocaine Infusion and Oral Tramadol on Pain During Diagnostic Office Hysteroscopy in Postmenopausal Women: Randomized Double-Blind Controlled Study [NCT03701984]	Phase 4	156 participants (Actual)	Interventional	2018-10-15	Completed
Postoperative Analgesia With Buprenorphine Transdermal System (BTDS) Versus Tramadol for Postoperative Pain Control and Quality of Life After Spinal Surgery [NCT02416804]	Phase 4	69 participants (Actual)	Interventional	2015-01-31	Completed
Comparison of the Therapeutic Efficacy and Side Effects of Tramadol Per os (Tradonal Odis® Orodispersible Tablets) Versus an Optimised Dosis of Intravenous Tramadol for Postoperative Pain Relief in Ambulatory Surgery. [NCT00735748]	Phase 4	195 participants (Actual)	Interventional	2008-03-01	Completed
Effect of Quadratus Lumborum Block on Postoperative Analgesic Requirements in Pediatric Patients: A Randomized Controlled Double Blinded Study [NCT03693222]		40 participants (Actual)	Interventional	2016-05-15	Completed
Time to Detox: A Patient-Centered Comparison of Length of Detoxification Treatment and Time to Naltrexone Maintenance Therapy in Opioid-Dependent Individuals [NCT03678792]	Phase 3	0 participants (Actual)	Interventional	2019-11-15	Withdrawn(stopped due to Infeasible to conduct at this time.)
Conscious Sedation Efficacy of the Novel Medication, MKO Melt (Midazolam, Ketamine, Ondansetron), During Cataract Surgery [NCT03653520]		651 participants (Actual)	Interventional	2017-06-28	Completed
Multimodal Anesthesia and Analgesia for Total Shoulder and Reverse Total Shoulder Arthroplasty: A Randomized Controlled Trial [NCT03586934]	Phase 3	0 participants (Actual)	Interventional	2018-06-01	Withdrawn(stopped due to Difficult to enroll patients for the study)
Efficacy of the Combination Mepivacaine-Tramadol on the Success of Inferior Alveolar Nerve Block in Patients With Symptomatic Irreversible Pulpitis: a Randomized Clinical Trial. [NCT02110966]	Phase 4	56 participants (Actual)	Interventional	2014-04-30	Completed
A MULTICENTER, RANDOMIZED, CONTROLLED STUDY OF EPIDURAL ANALGESIA FOR SEVERE ACUTE PANCREATITIS [NCT02126332]	Phase 3	148 participants (Actual)	Interventional	2014-06-06	Completed
Prospective Controlled Study of Surgical Management of Unstable Thoracic Cage Injuries and Chest Wall Deformity in Trauma [NCT02132416]		92 participants (Actual)	Interventional	2014-05-31	Completed
The Relationship Between Patient Preferences, Analgesic Delivery Method and Pain Reduction in Spine Patients [NCT01263652]		0 participants (Actual)	Interventional	2010-12-31	Withdrawn(stopped due to inability to complete recruitment as planned)
Study of Non-pharmacokinetic Interaction Between Diclofenac 25 mg and 25 mg Tramadol With the Fixed-dose Combination Tablets of the Two Drugs Administered to Healthy Subjects of Both Genders in Fasting State [NCT03766984]	Phase 1	36 participants (Actual)	Interventional	2015-06-07	Completed
A Single Dose Pharmacokinetic, Tolerability, and Safety Study of ULTRAM ER at Two Dose Levels in Children Seven to Eleven Years Old, Inclusive, With Pain [NCT01586494]	Phase 1	37 participants (Actual)	Interventional	2007-10-31	Completed
[NCT00942565]	Phase 4	60 participants (Actual)	Interventional	2007-04-30	Completed
Multimodal Nonopioid Pain Protocol Following Shoulder Arthroplasty Surgery [NCT05488847]	Phase 4	80 participants (Anticipated)	Interventional	2022-06-25	Recruiting
[NCT00643383]	Phase 3	277 participants (Actual)	Interventional	2008-03-31	Completed
Effects of Midazolam or Tramadol Premedication on Early Cognitive Function in ERCP: a Randomized Controlled Double-Blind Study [NCT02436980]	Phase 4	40 participants (Actual)	Interventional	2009-01-31	Completed
Does Gabapentin Reduce Quadriceps Muscle Weakness After Anterior Cruciate Ligament Reconstruction? A Randomised Controlled Trial [NCT03496389]	Phase 2/Phase 3	30 participants (Anticipated)	Interventional	2018-07-01	Not yet recruiting
A Multi-Center, Randomized, Double-Blind, Placebo/Active-Controlled Phase III Clinical Study to Evaluate the Efficacy and Safety of HSK21542 Injection for Postoperative Pain Treatment [NCT05390905]	Phase 3	387 participants (Actual)	Interventional	2022-06-08	Completed
Comparing Protocols for Analgesia Following Elective Cesarean Section [NCT03622489]	Phase 4	120 participants (Anticipated)	Interventional	2017-03-01	Recruiting
Safety and Efficacy of Tramadol Adjuvant Therapy to Standard Care for COVID-19 Egyptian Patients: A Randomized Double Blind Controlled Clinical Trial [NCT04454307]	Phase 1/Phase 2	100 participants (Anticipated)	Interventional	2020-07-31	Not yet recruiting
Are Narcotic Pain Medications Necessary Following Thyroidectomy and Parathyroidectomy [NCT03640247]	Phase 1	126 participants (Actual)	Interventional	2018-11-15	Completed
National, Multicentre, Randomized, Double-blind, Triple-dummy Active-Controled Phase III Clinical Trial to Evaluate the Efficacy and Safety of APSCTC for the Treatment of Postsurgical Pain Due to Third Molar Extraction. [NCT04647435]	Phase 3	396 participants (Anticipated)	Interventional	2023-05-13	Recruiting
A Phase 1 Randomized, Double-Blind, Placebo-Controlled, Triple Cross-Over Study Investigating The Safety, Oral Steady-State Pharmacokinetics, And Clinical Activity Of 20 Mg Omnitram And 50 Mg Tramadol In Normal Human Subjects [NCT02205554]	Phase 1	43 participants (Actual)	Interventional	2014-08-31	Completed
[NCT02291705]	Phase 4	40 participants (Actual)	Interventional	2012-01-31	Completed
Radiofrequency Thoracic Sympathectomy for Chronic Postmastectomy Pain; Randomized Placebo Controlled Study [NCT03494426]		70 participants (Actual)	Interventional	2018-04-01	Completed
Analgesic Efficacy of Oral Dexketoprofen Trometamol/Tramadol Hydrochloride Versus Tramadol Hydrochloride/Paracetamol: a Randomised, Double-blind, Placebo and Active-controlled, Parallel Group Study in Moderate to Severe Acute Pain After Removal of Impacte [NCT02777970]	Phase 4	654 participants (Actual)	Interventional	2016-04-30	Completed
The Effect of Tramadol on Interscalene Brachial Plexus Block With Ropivacaine in Shoulder Surgery. [NCT02182752]	Phase 2	80 participants (Actual)	Interventional	2013-04-30	Completed
A Randomized, Double-Blind, Multicenter, Placebo- and Active Comparator-Controlled Study to Evaluate Efficacy and Safety of MR308 in the Treatment of Acute Pain After Abdominal Hysterectomy Surgery Under General Anaesthesia (STARDOM2). [NCT03062644]	Phase 3	1,138 participants (Actual)	Interventional	2017-04-05	Completed
Oral Tramadol Versus Oral Celecoxib for Post-perineal Repair Analgesia After Spontaneous Vaginal Birth in Obese Women: A Randomised Controlled Trial [NCT03694873]	Phase 4	200 participants (Anticipated)	Interventional	2018-10-10	Not yet recruiting
Comparison Between USG-Guided Infiltration Popliteal Artery Capsule Knee Block Versus Adductor Canal Block Application as Postoperative Analgesia in Total Knee Prosthesis Under General Anesthesia: Randomized Clinical Trial [NCT05956275]	Phase 4	20 participants (Actual)	Interventional	2020-12-08	Completed
Comparison of Tramadol vs. Tramadol With Paracetamol for Efficacy of Postoperative Pain Management in Lumbar Discectomy: A Randomised Controlled Trial [NCT03482492]		60 participants (Actual)	Interventional	2014-03-20	Completed
The Effect of Preoperative Anxiety Level to Postoperative Pain and Analgesic Consumption in Patients Who Had Laparoscopic Sleeve Gastrectomy [NCT04432558]		42 participants (Actual)	Observational [Patient Registry]	2017-04-12	Completed
Minimizing Narcotic Analgesics After Thyroid or Parathyroid Surgery [NCT03469310]	Phase 4	126 participants (Actual)	Interventional	2018-03-09	Completed
Risk of Phenoconversion in Genetic Extensive Metabolizers Healthy Volunteers Carriers of One Fully-Functional and One Non-Functional Allele Versus Carriers of Two Fully-Functional Alleles [NCT03054220]		34 participants (Actual)	Interventional	2016-07-31	Completed
Comparison of Post-Operative Analgesia With Peri Tract Local Anesthesia Infiltration and Oral Analgesia Versus Post-Operative Intravenous Analgesia After Percutaneous Nephrolithotomy. [NCT04835116]	Phase 4	68 participants (Actual)	Interventional	2019-04-11	Completed
Role of Tramadol 50mg in Reducing Pain Associated With Outpatient Hysteroscopy: A Randomized Double Blind Placebo Controlled Trial. [NCT02068209]	Phase 2	140 participants (Actual)	Interventional	2014-05-31	Completed
Analgesic Efficacy of Trans Abdominis Plane Block in Women Undergoing Cesarean Section: a Randomized Study. [NCT04809532]		60 participants (Anticipated)	Interventional	2021-02-25	Recruiting
Comparison of the Efficacy of Intravenous Dexmedetomidine and Tramadol in Control of Post Spinal Shivering in Obstetric Patients Undergoing Lower Segment Cesarean Section [NCT05616364]	Phase 2	100 participants (Anticipated)	Interventional	2023-03-31	Not yet recruiting
A Prospective Randomized Controlled Trial of Pain as Indication for Operative Treatment of Traumatic Rib Fractures. [NCT02094807]		0 participants (Actual)	Interventional	2014-04-30	Withdrawn(stopped due to Slow inclusion rate. Awaiting results from NCT02132416.)
A Randomized, Double-Blind, Placebo- and Positive-Controlled, Multiple Dose, Four Way Crossover Study to Evaluate the Effects of Tramadol Hydrochloride on Cardiac Repolarization in Healthy Subjects at Therapeutic and Supratherapeutic Dose Levels [NCT02307864]	Phase 1	68 participants (Actual)	Interventional	2014-12-04	Completed
Effect of Increased Pain Tolerance on Exercise Performance [NCT03934411]		16 participants (Actual)	Interventional	2018-03-01	Completed
[NCT00834912]	Phase 1	36 participants (Actual)	Interventional	2006-02-28	Completed
Efficacy and Safety of Intravenous Tramadol Versus Intravenous Paracetamol for Relief of Acute Pain of Primary Dysmenorrhea: A Randomized Controlled Trial [NCT03509740]	Phase 4	100 participants (Actual)	Interventional	2018-04-25	Completed
[NCT01178203]	Phase 1/Phase 2	0 participants	Interventional	2010-07-31	Completed
Pharmacokinetic Non-interaction Study Between Pregabalin 150 mg and Tramadol 50 mg, Administered Individually or in Combination, Single Dose in Healthy Subjects of Both Genders Under Fasting Conditions [NCT05389150]	Phase 1	30 participants (Actual)	Interventional	2019-01-17	Completed
A PHASE IV, OPEN LABEL, RANDOMIZED, TWO TREATMENT, TWO PERIOD, TWO SEQUENCE, CROSSOVER BIOEQUIVALENCE STUDY TO COMPARE AN ORAL FORMULATION OF TRAMADOL HYDROCHLORIDE 37.5 MG/PARACETAMOL 325 MG TABLETS (TEST PRODUCT OF PFIZER) VERSUS ULTRACET(REGISTERED) (T [NCT03803371]	Phase 4	60 participants (Actual)	Interventional	2019-03-26	Completed
Comparative Study Between Preemptive and Postoperative Intra-articualr Injection of Levobupivacaine and Tramadol [NCT03785041]		220 participants (Actual)	Interventional	2016-12-21	Completed
A Single Dose Pharmacokinetic, Tolerability, and Safety Study of ULTRAM ER at Two Dose Levels in Adolescents Twelve to Seventeen Years Old, Inclusive, With Pain [NCT01586507]	Phase 1	38 participants (Actual)	Interventional	2007-10-31	Completed
Is Postoperative Quality of Recovery After Unilateral Nephrectomy Related to the Type of Anesthesia and Analgesia? [NCT04521556]	Phase 4	80 participants (Actual)	Interventional	2019-04-01	Completed
Combined On-demand Sildenafil Citrate and Tramadol Hydrochloride for Treatment of Premature Ejaculation: A Randomized Placebo-controlled Double-blind Clinical Trial [NCT05183334]	Phase 4	160 participants (Anticipated)	Interventional	2021-12-30	Not yet recruiting
A Phase 3 Study of JNS013 in Patients With Chronic Pain [NCT00736853]	Phase 3	321 participants (Actual)	Interventional	2008-06-30	Completed
[NCT02674737]		80 participants (Anticipated)	Interventional	2016-01-31	Recruiting
Ultrasound-Guided Bilateral Thoracic Paravertebral Blocks as an Adjunct to General Anaesthesia in Patients Undergoing Reduction Mammoplasty: A Historical Cohort Study [NCT02671851]		64 participants (Actual)	Observational	2014-01-31	Completed
A Randomized Controlled Trial to Compare the Efficacy of Medicine Conservative Treatment and Surgical Treatment for Symptomatic Sacral Perineurial Cysts (Tarlov Cysts) and the Applied Value of Resting State Functional Magnetic Resonance Imaging (rfMRI). [NCT02595190]	Phase 4	96 participants (Anticipated)	Interventional	2015-03-31	Recruiting
A Randomized, Double-Blind, Placebo And Active Controlled Methodology Study Investigating The Effects Of Tramadol And Naproxen On The Pain Thresholds Of Patients With Severe Pain Due To Osteoarthritis Of The Thumb [NCT00743587]	Phase 1	36 participants (Actual)	Interventional	2008-09-30	Completed
Evaluation Of The Efficacy Of A Bolus Infiltration Of The Anaesthetic Tramadol Associated With Continuous Local Anaesthesia Administered Via A Wound Catheter Following Heart Surgery Via Sternotomy At Dijon Chu Single-Centre, Double-Blind, Randomized, Cont [NCT02851394]	Phase 4	160 participants (Actual)	Interventional	2015-10-31	Completed
A Randomized, Double-Blind, Placebo-Controlled Dose Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics Following Multiple Ascending Doses of Tramadol Hydrochloride in Healthy Male and Female Subjects [NCT01947920]	Phase 1	30 participants (Actual)	Interventional	2013-08-31	Completed
The Impact of Intravenous Anaesthesia on Angiogenesis in Patients With Breast Cancer [NCT02839668]	Phase 2	120 participants (Actual)	Interventional	2016-08-31	Completed
Clinical Trial to Compare the Pharmacokinetics Profile of YJAT Sustained Release Tablet and ULTRACET® Immediate Release Tablet After Oral Administration to Healthy Male Subjects [NCT01880125]	Phase 1	24 participants (Actual)	Interventional	2012-01-31	Completed
Effects of Sleep Quality on Melatonin Levels and Inflammatory Response After Major Abdominal Surgery in an Intensive Care Unit [NCT02824770]		40 participants (Anticipated)	Interventional	2017-01-01	Recruiting
Clinical Evaluation of Penthrox (Methoxyflurane)and Tramadol for the Singapore Emergency Ambulance Service [NCT01887951]	Phase 4	380 participants (Actual)	Interventional	2014-02-28	Completed
Tramadol for Labour Analgesia in Low Risk Primiparous Women. Double Blind, Randomized, Controlled Trial. [NCT01889979]	Phase 3	100 participants (Actual)	Interventional	2012-10-31	Completed
Cognitive Function and Addiction in Patients With Chronic Pain Under Opioid Tapering in a Multidisciplinary Pain Treatment [NCT03365817]	Phase 3	75 participants (Actual)	Interventional	2009-02-02	Completed
Comparison of Different Strategies in Preventing Discomfort Due to Urine Catheter in Urinary Surgery [NCT04314050]		135 participants (Actual)	Interventional	2020-03-10	Completed
A Phase 1b, Double-Blind, Randomized, Placebo-Controlled, Three Segment Cross-Over Study Investigating Oral Steady-State Pharmacokinetics And Hypoalgesic Effect Of 20 Mg Omnitram And 50 Mg Tramadol In Normal Human Subjects Made Cyp2d6 Deficient By Paroxet [NCT03312777]	Phase 1	60 participants (Actual)	Interventional	2017-10-31	Completed
Analgesic Effect of Ultrasound Guided Quadratus Lumborum Block Application After Laparoscopic Cholecystectomy Surgery [NCT03308955]		60 participants (Actual)	Interventional	2017-08-22	Completed
Confirmatory Efficacy and Safety Study of the Fixed-dose Combination of Etoricoxib / Tramadol Versus Acetaminophen / Tramadol for the Management of Acute Low Back Pain. [NCT04968158]	Phase 3	124 participants (Actual)	Interventional	2021-11-29	Completed
Tramadol Versus Celecoxib for Reducing Pain Associated With Outpatient Hysteroscopy: A Randomized Double Blind Placebo-Controlled Trial [NCT02071303]	Phase 2	210 participants (Actual)	Interventional	2014-05-31	Completed
Doses Tramadol With Bupivacaine in Penial Block Improve Efficiency of Postoperative Analgésia in Children in Circumcision [NCT03260439]		106 participants (Actual)	Interventional	2014-06-30	Completed
The Effect of Intravenous Paracetamol in Combination With NSAIDs for Postoperative Pain in Children [NCT02248493]	Phase 4	54 participants (Actual)	Interventional	2012-11-30	Completed
A Comparison of Postoperative Tramadol/Gabapentin/Ibuprofen Versus Tramadol/Placebo/Ibuprofen in Children Undergoing Tonsillectomy [NCT02076893]	Phase 4	64 participants (Actual)	Interventional	2014-03-31	Terminated(stopped due to Interim analysis results indicated need to recruit beyond scope of budget.)
Nefopam vs Tramadol in the Prevention of Post Anaesthetic Shivering Following Subarachnoid Block [NCT02441673]	Phase 2	130 participants (Anticipated)	Interventional	2018-10-12	Not yet recruiting
A Multicenter,Randomized, Double-blind, Dose Ranging , Active- and Placebo-controlled, Parallel Groups, Phase II Clinical Trial to Evaluate the Efficacy and Safety of HR18042 Tablets for the Treatment of Postoperative Pain of Impacted Tooth. [NCT04812860]	Phase 2	187 participants (Actual)	Interventional	2020-12-08	Active, not recruiting
Comparison of the Analgesic Effects of Tramadol, Pethidine and Morphine Under Erector Spinae Plane (ESP) Block in the Treatment of Pain After Elective Thoracic Surgery [NCT06172920]	Phase 4	45 participants (Anticipated)	Interventional	2023-12-31	Not yet recruiting
Effect of Continue Rhomboid Intercostal and Subserratus Plane Block in Thorocotomy [NCT04443556]		40 participants (Actual)	Interventional	2020-08-31	Completed
PROUD Study - Preventing Opioid Use Disorders [NCT04766996]	Phase 4	57 participants (Actual)	Interventional	2021-05-17	Terminated(stopped due to Loss of surgery team member deemed the study procedures impossible to achieve, and no replacement could be found in a timely manner to complete trial as initially planned.)
Randomised Double Blind Comparison of Prophylactic Tramadol and Tramadol Plus Ketamine for Prevention of Shivering After Spinal Anesthesia in Lower Segment Caeserian Section [NCT06134895]	Phase 4	190 participants (Anticipated)	Interventional	2023-08-16	Recruiting
Effect of Tramadol on Postoperative Sore Throat in Thyroid Surgery Under General Anesthesia With Endotracheal Intubation: A Randomized Controlled Trial [NCT04991493]	Phase 4	168 participants (Anticipated)	Interventional	2021-09-10	Recruiting
Open-label Study of the Safety and Effectiveness of Short-term Therapy With Extended-release Tramadol (TRAMADEX-OD) in the Management of Pain After Knee Arthroscopy. [NCT01024348]		100 participants (Anticipated)	Interventional	2009-12-31	Not yet recruiting
A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Efficacy and Safety of Two Doses of Tramadol Hydrochloride Orally Disintegrating Tablets in Male Subjects With Premature Ejaculation [NCT00983736]	Phase 3	1,050 participants (Anticipated)	Interventional	2009-10-31	Terminated(stopped due to This study was terminated because of recruitment difficulties.)
A Randomised Open Label Parallel Group Study Comparing Norspan Patch and Oral Tramadol [NCT01019265]	Phase 4	170 participants (Actual)	Interventional	2008-03-31	Completed
A Single-Centre, Open-Label, Randomised Study to Compare the Single Dose (Including the Effect of Food) and Multiple Dose Pharmacokinetic Profiles of Acetram Contramid® BID Tablets vs the Immediate-Release Tablet Reference Products Zaldiar® and Ultracet® [NCT00973232]	Phase 1	58 participants (Actual)	Interventional	2008-05-31	Completed
The Effect of Prolonged Multimodal Analgesic Regimen on Post Hospital Discharge Opioid Use and Pain Control After Primary Total Knee Arthroplasty [NCT04003350]		216 participants (Actual)	Interventional	2017-12-21	Completed
Demonstration of OTC Naproxen Sodium's (Aleve's) Anti-inflammatory Action in Dental Implant Surgery Patients [NCT04694300]	Phase 4	32 participants (Actual)	Interventional	2021-02-07	Completed
Paroxetines Effect on Tramadols Metabolism and Pharmakodynamics: a Dose Response Study [NCT00785603]	Phase 4	12 participants (Actual)	Interventional	2008-08-31	Active, not recruiting
Role of Oral Tramadol 50 mg in Reducing Pain During Colposcopy-directed Cervical Biopsy: A Randomised Double-blind Placebo-controlled Trial [NCT03532841]		250 participants (Anticipated)	Interventional	2018-05-15	Not yet recruiting
Comparison of Tramacet Versus Percocet in Post Surgical Patients [NCT02361567]	Phase 4	160 participants (Actual)	Interventional	2015-04-30	Completed
Oral Tramadol Versus Diclofenac For Pain Relief Before Outpatient Hysteroscopy: A Randomized Controlled Trial [NCT02760888]	Phase 3	102 participants (Anticipated)	Interventional	2016-05-31	Not yet recruiting
A Comparison of the Analgesic Efficacy and Safety of Once Daily Tramadol HCl / Contramid® Tablets to Twice Daily Tramadol HCl (SR) for the Treatment of Osteoarthritis of the Knee. [NCT00950651]	Phase 3	431 participants (Actual)	Interventional	2002-03-31	Completed
Intraoperative and Postoperative Effects of Adjuvant Dexmedetomidine and Tramadol in Subcostal Transversus Abdominis Plan Block [NCT05905757]		60 participants (Actual)	Interventional	2022-03-01	Completed
Effects of Duloxetine on Pain Relief After Total Knee Arthroplasty in Central Sensitization Patient : A Randomized, Controlled, Double-Blind Trial [NCT02600247]		100 participants (Anticipated)	Interventional	2015-11-30	Not yet recruiting
Validation of a New Method to Detect CYP2D6 Poor Metabolizers by Monitoring Seric Concentrations of O-demethyl-tramadol and Tramadol to Make a Ratio in Comparison With Genotyping in Post-operative Patients Treated With Intravenous Tramadol [NCT00952159]		301 participants (Actual)	Observational	2010-04-30	Completed
Health - Related Quality of Life in Patients With Rheumatic Diseases Taking Tramadol 37.5mg/Acetaminophen 325mg Tablets ; Multicenter, Open-label, Prospective, Observational Study [NCT00642837]		982 participants (Actual)	Observational	2007-09-30	Completed
EVALUATION OF ORAL USE OF DEXKETOPROFEN/TRAMADOL IN ACUTE POSTOPERATIVE PAIN IN PATIENTS UNDERGOING TOTAL HIP REPLACEMENT WITH A MINIMALLY INVASIVE ANTERIOR APPROACH (AMIS). [NCT04178109]	Phase 2	226 participants (Actual)	Interventional	2019-01-10	Completed
Comparison of Two Combinations of Opioid and Non-opioid Analgesics for Acute Periradicular Abscess: A Randomized Clinical Trial [NCT02750696]		27 participants (Actual)	Interventional	2013-04-30	Completed
Treatment of Neuropathic Pain in Leprosy: a Randomized Double Blind Controlled Study [NCT03324035]	Phase 3	102 participants (Actual)	Interventional	2017-03-01	Active, not recruiting
To Compare the Relative Bioavailability of the Kali's Tramadol APAP Tablets With Ortho-McNeil's Ultracet Tablets Under Fed Conditions. [NCT00652821]	Phase 1	22 participants (Actual)	Interventional	2002-05-31	Completed
Effect of Opioids and NSAIDs on Sympathetic Nervous System and Vascular Function in Healthy Subjects and Patients With Osteoarthritis [NCT03781544]	Phase 4	90 participants (Anticipated)	Interventional	2019-01-01	Recruiting
[NCT02670954]		154 participants (Actual)	Interventional	2015-10-31	Completed
Tramadol Versus Celecoxib in Reducing Pain Associated With IUD Insertion: A Double Blind Placebo Controlled Trial [NCT02827487]	Phase 4	210 participants (Anticipated)	Interventional	2016-07-01	Recruiting
Comparison of Pudendal Nerve Block With Ropivacaine and Intravenous Tramadol for Prevention of Catheter-related Bladder Discomfort: a Randomized Controlled Trial [NCT02683070]		94 participants (Anticipated)	Interventional	2016-03-31	Not yet recruiting
Effect of Wound Infiltration With Tramadol, Dexmedetomidine, or Magnesium Sulfate as Adjuncts to the Local Anesthetic on Pain Relief After Spine Surgery [NCT04391855]	Phase 4	72 participants (Actual)	Interventional	2020-05-10	Completed
The Effect of the Combined Use of Naloxone and Tramacet on Postoperative Analgesia in Elderly Patients Having Joint Replacement Surgery: a Randomized Controlled Study. [NCT00679614]	Phase 3	45 participants (Actual)	Interventional	2007-12-17	Completed
Tramadol Versus Celecoxib for Reducing Pain During Operative Office Hysteroscopy: A Double Blind Placebo Controlled Trial. [NCT02736071]	Phase 3	210 participants (Anticipated)	Interventional	2016-06-30	Recruiting
The Effect of Intravenous Infusion of Tramadol-ondansetron on Recovery After Caesarean Section. A Prospective, Observational and Non-inferiority Study Against Epidural Analgesia. [NCT05879536]		312 participants (Anticipated)	Observational	2023-05-23	Recruiting
Medications Development for Drug Abuse Disorders [NCT00499746]	Phase 1/Phase 2	20 participants (Actual)	Interventional	2007-11-30	Completed
Development of Cocktail for Measuring the Activity of Important Cytochrome P450 Enzymes [NCT00981929]		412 participants (Anticipated)	Interventional	2009-09-30	Terminated(stopped due to Unexpected non-serious adverse events)
A Two Part Protocol Using Double Blind Placebo Control to Assess the Safety, Tolerability, and Pharmacokinetics of Single Escalating Intra-articular Doses Followed by Assessment of Efficacy, Safety, Tolerability and Pharmacokinetics of a Single Intra-arti [NCT02845271]	Phase 2	104 participants (Actual)	Interventional	2016-07-21	Completed
Efficacy of Adding Tramadol as Adjunctive Analgesic With Levobupivacaine in Modified Pectoral Nerve Block for Modified Radical Mastectomy Surgery [NCT02625506]		60 participants (Actual)	Interventional	2012-06-01	Completed
[NCT00852917]	Phase 3	552 participants (Actual)	Interventional	2003-01-31	Completed
To Compare the Relative Bioavailability of the Kali's Tramadol APAP Tablets With Ortho-McNeil's Ultracet Tablets Under Fasting Conditions. [NCT00653315]	Phase 1	28 participants (Actual)	Interventional	2002-05-31	Completed
[NCT00832416]	Phase 3	565 participants (Actual)	Interventional	2003-01-31	Completed
A Study to Evaluate the Clinical Benefits of Tramadol/Acetaminophen (Ultracet®) vs. Diclofenac (Voltaren®) in the Treatment of Pain in Patients With Ankylosing Spondylitis Receiving Stable Treatment of Disease Modifying Anti-rheumatic Drugs (DMARDs) [NCT00766402]	Phase 4	8 participants (Actual)	Interventional	2008-10-31	Terminated
A Double-Blind Comparative Study of JNS013 in Patients With Post-Tooth-Extraction Pain [NCT00737048]	Phase 3	328 participants (Actual)	Interventional	2008-03-31	Completed
An Exploratory Study of an Active Ingredient of JNS013-tramadol Hydrochloride in Patients With Osteoarthritis of the Knee or Low Back Pain [NCT00752661]	Phase 2	119 participants (Actual)	Interventional	2007-06-30	Completed
Post-Operatory Analgesia in Newborn Infants: a Comparative Study of Fentanyl Versus Tramadol [NCT00713726]	Phase 3	160 participants (Actual)	Interventional	2006-01-31	Completed
Tramadol and Pain Sensitization [NCT00487175]	Phase 1	12 participants (Anticipated)	Interventional	2007-09-30	Completed
Opioid Consumption Following TAP Block Versus Intraperitoneal/Incisional Bupivicaine in Patients Undergoing Major Gynecologic Surgeries: A Randomized Controlled Trial [NCT04037878]		135 participants (Actual)	Interventional	2017-11-20	Completed
Use of Tramadol Injections on the Anaesthetic Success Rate of Intraligamentary Injections in Patients With Symptomatic Irreversible Pulpitis [NCT05538052]		105 participants (Actual)	Interventional	2022-04-01	Completed
The Effect of Escitalopram on the Pharmacokinetics and Pharmacodynamics of Tramadol in Healthy Subjects [NCT00692263]	Phase 4	15 participants (Actual)	Interventional	2008-02-29	Completed
Randomized Control Trial. Comparative Effectiveness Study for Surgery vs. Non-Surgery in Patients With Low Back Pain [NCT02883569]		1,102 participants (Actual)	Interventional	2016-09-30	Completed
An Open-Label Long-term Safety Study of Tramadol HCl OAD (Once A Day) 300 mg in the Treatment of Pain Due to Osteoarthritis of the Knee [NCT00833911]	Phase 3	392 participants (Actual)	Interventional	2003-04-30	Completed
Transversus Abdominis Plane Block Versus Quadratus Lumborum Block for Postoperative Analgesia in Pediatric Patients; a Prospective, Randomized, Controlled Study [NCT04209478]		40 participants (Actual)	Interventional	2016-05-01	Completed
Effect of Preoperative Tramadol and Naproxen Sodium on Efficacy of Local Anesthesia and Post-operative Pain in Patients With Symptomatic Irreversible Pulpitis [NCT05982392]	Phase 2/Phase 3	47 participants (Actual)	Interventional	2023-03-01	Completed
A Methodology Study To Assess The Feasibility Of Using Functional Magnetic Resonance Imaging (fRMI) To Quantify The Effects Of Analgesic Drugs In Post-Traumatic Neuropathic Pain Subjects [NCT00610155]		18 participants (Actual)	Interventional	2008-09-30	Completed
Continuous Erector Spinae Plane Local Anesthetic Infusion for Postoperative Analgesia in Pediatric Patients Undergoing Nephrectomy: Randomized Controlled Study [NCT04613830]	Phase 3	60 participants (Actual)	Interventional	2020-11-20	Completed
[NCT00833794]	Phase 3	1,028 participants (Actual)	Interventional	2004-10-31	Completed
Transdermal Buprenorphine for the Treatment of Radiation-Induced Mucositis Pain in Head and Neck Cancer Patients: A Pilot Study [NCT04752384]	Phase 2	20 participants (Anticipated)	Interventional	2021-07-08	Recruiting
Large-scale Prospective Double-blind Randomized Controlled Trial of Pecs II Block for Breast Surgery: Effect on Postoperative Pain and Opioid Consumption [NCT02544282]	Phase 4	140 participants (Actual)	Interventional	2014-04-30	Completed
The Effect of Anti-inflammatory Analgesics on Bone Repair, Pain and Gastro-intestinal Side Effects After Hallux Valgus Surgery; a Prospective Randomised Double-blind Placebo Controlled Study. [NCT00733421]	Phase 4	100 participants (Actual)	Interventional	2008-10-31	Completed
Fast-Release Orodispersible Tramadol Tablet (Tradonal Odis®) as Analgesia for Hysterosalpingography : a Randomized, Controlled, Double Blinded Study [NCT00893412]	Phase 4	128 participants (Actual)	Interventional	2008-11-30	Completed
A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Efficacy and Safety of Two Doses of Tramadol Hydrochloride Orally Disintegrating Tablets in Male Subjects With Premature Ejaculation [NCT00983151]	Phase 3	1,050 participants (Anticipated)	Interventional	2009-08-31	Terminated
Tolerability Improvement of Tramadol/Acetaminophen (Ultracet) by Titration in Korean OA Patients:Multicenter, Randomized, Double-blind Study [NCT01063842]	Phase 4	250 participants (Actual)	Interventional	2005-08-31	Completed
The Effect of Addition of Tramadol to Levobupivacaine in Continuous Wound Infusion for Postoperative Pain Treatment in Cesarean Section [NCT01916915]	Phase 4	65 participants (Actual)	Interventional	2013-07-31	Completed
Assessment of the Level of Physical Dependence and Blockade Efficacy Produced by Tramadol [NCT00301210]	Phase 1/Phase 2	9 participants (Actual)	Interventional	2006-01-31	Completed
Evaluation of the Analgesic Effect of Tramadol Wound Infiltration in Children Under Inguinal Hernioplasty. A Double-blind, Randomized Study. [NCT01943760]	Phase 4	40 participants (Actual)	Interventional	2012-09-30	Completed
ULTRACET (Tramadol Hydrochloride and Acetaminophen) add-on Therapy for the Treatment of the Pain of Rheumatoid Arthritis: A Randomized, Double-blind, Placebo-controlled Study [NCT00246168]	Phase 4	277 participants (Actual)	Interventional		Completed
A Study of Safety and Efficacy of Ultracet in Patients With Chronic Cancer Pain [NCT01968018]	Phase 4	35 participants (Actual)	Interventional	2004-07-31	Completed
Comparison of Normotensive Anesthesia Using a Combination of Metoprolol and Tramadol With Controlled Hypotension Using Remifentanil in Endoscopic Sinus Surgery [NCT02484859]	Phase 4	88 participants (Actual)	Interventional	2015-07-31	Completed
Non-Steroidal Anti-inflammatory Drugs (NSAIDS) vs. Tramadol in Pain Management After Transnasal Transsphenoidal Surgery Among Patients With Pituitary Adenomas: A Prospective Randomized Controlled Trial [NCT04611685]		202 participants (Anticipated)	Interventional	2020-10-31	Recruiting
Comparison Between the Effect of Tramadol Versus Morphine on PD1 and PD1-ligand in Patients With Chronic Cancer Pain [NCT04589494]	Phase 2/Phase 3	15 participants (Anticipated)	Interventional	2020-04-16	Recruiting
Is Postoperative Quality of Recovery After Radical Prostatectomy Related to the Type of Anesthesia and Analgesia? [NCT04587505]	Phase 4	61 participants (Actual)	Interventional	2019-04-01	Completed
A Phase 3, Multicenter, Randomized, Double Blind, Three-Arm Study to Evaluate the Efficacy and Safety of Tramadol Infusion (AVE-901) Versus Placebo in the Management of Postoperative Pain Following Bunionectomy [NCT03290378]	Phase 3	409 participants (Actual)	Interventional	2017-09-19	Completed
Comparison of Analgesic Efficacy of Topical Tramadol Versus Topical Lidocaine in the Control of Post Operative Pain in Children After Tonsillectomy [NCT05928520]	Phase 3	80 participants (Anticipated)	Interventional	2023-08-01	Not yet recruiting
Impact of Tramadol and Oxycodone on Sleep Apnea [NCT03454217]	Phase 4	60 participants (Actual)	Interventional	2018-03-01	Completed
An Open Label Study to Evaluate Safety, Tolerability and Clinical Utility of ULTRACET® (37.5mg Tramadol Hydrochloride/325mg Acetaminophen) for the Treatment of Breakthrough Pain in Cancer Patients [NCT00576173]	Phase 4	60 participants (Actual)	Interventional	2005-12-31	Completed
Tramadol Versus Celecoxib for Reducing Pain During Office Hysteroscopy in Post Menopausal Women: A Double Blind Randomized Controlled Trial [NCT02736019]	Phase 3	210 participants (Anticipated)	Interventional	2016-06-30	Recruiting
[NCT00834366]	Phase 1	26 participants (Actual)	Interventional	2005-02-28	Completed
A Randomized, Open Label, 2-treatment, 2-sequence, Cross-over Study to Compare the Safety and Pharmacokinetics of DW-0919 and DW-0920 After Single Oral Administration in Healthy Male Volunteers [NCT01606059]	Phase 1	30 participants (Actual)	Interventional	2012-05-31	Completed
Evaluation of Multimodal Oral Strategies Using Sequential Analysis (Tramadol, Opioid) After Shoulder Ambulatory Surgery [NCT04110665]	Phase 4	200 participants (Anticipated)	Interventional	2017-09-01	Recruiting
Comparative Randomized, Single Dose, Two-Way Crossover Open Label Study To Determine The Bioequivalence Of 5 mg/mL Tramadol Hydrochloride Oral Solution (08P1902F0) Relative To Contramal® (100 mg/mL Oral Solution) After An Oral Administration [NCT05716763]	Phase 1	24 participants (Actual)	Interventional	2023-02-14	Completed
A Six Week Double-Blind, Randomized, Multicenter Comparison Study Of The Analgesic Effectiveness Of Celecoxib 200 Mg BID Compared To Tramadol Hydrochloride 50 Mg QID In Subjects With Chronic Low Back Pain [NCT00662558]	Phase 3	802 participants (Actual)	Interventional	2008-01-31	Completed
"Comparison Between the Analgesic Affects of Tramadol® and Verbal Anesthesia on Pain Management Associated With the Insertion of Jaydess® in Nulliparous Women" [NCT02706509]	Phase 4	100 participants (Anticipated)	Interventional	2016-03-31	Not yet recruiting
Randomized, Double-blind, Double-dummy, Active Controlled, Multicentre, Non-inferiority Phase-III Study to Compare Gabapentin Liquid Formulation to Tramadol in Children Experiencing Moderate to Severe Chronic Neuropathic or Mixed Pain [NCT02722603]	Phase 3	2 participants (Actual)	Interventional	2018-09-12	Terminated(stopped due to The study was early terminated due to insufficient recruitment)
Comparison Of Immune Response And Analgesic Effects Of Caudally Administrated Tramadol In Pediatric Lower Abdominal Surgery [NCT02703415]	Phase 2	60 participants (Actual)	Interventional	2016-06-30	Completed
Effects of Addition of Systemic Tramadol or Adjunct Tramadol to Lidocaine Used for Intravenous Regional Anesthesia in Patients Undergoing Hand Surgery [NCT02658721]	Phase 3	60 participants (Actual)	Interventional	2013-01-31	Completed
Safety and Efficacy of Oral Tramadol Administration in Reducing Pain During Levonorgestrel Intrauterine Device Insertion in Adolescents and Young Women: a Randomized Controlled Trial [NCT04312061]	Phase 3	108 participants (Anticipated)	Interventional	2020-03-30	Not yet recruiting
A Randomized, Placebo-Controlled, Parallel Group, Double-Blind Clinical Study to Evaluate the Efficacy and Safety of Tramadol HCl/Acetaminophen Extended Release Tablet in Subjects With Chronic Low Back Pain [NCT01112267]	Phase 3	248 participants (Actual)	Interventional	2009-05-31	Completed
A Phase 3, Multicenter, Single-Arm, Open-Label Study to Evaluate the Safety of Tramadol Infusion (AVE-901) in the Management of Post-Operative Pain Following Surgery [NCT03395808]	Phase 3	251 participants (Actual)	Interventional	2017-12-22	Completed
A Selective COX-2 Inhibitor Provides Pain Control But Hinders Healing Following Arthroscopic Rotator Cuff Repair: A Prospective Randomized Comparison [NCT02850211]	Phase 4	180 participants (Actual)	Interventional	2011-09-30	Completed
A Comparison of the Analgesic Efficacy and Safety of Once Daily Tramadol OAD Tablets to Twice Daily Tramadol BID for the Treatment of Osteoarthritis of the Knee (Extension Protocol) and Open Label Safety Follow-Up [NCT00912015]	Phase 3	238 participants (Actual)	Interventional	2002-03-31	Completed
A Pharmacodynamic/Pharmacokinetic Study to Determine the Onset of Analgesic Effect and Plasma Levels of Tramadol in Patients With Acute Low Back Pain Receiving a Single 200 mg Dose of Tramadol Contramid® Once-a-Day [NCT00952068]	Phase 2	47 participants (Actual)	Interventional	2007-01-31	Completed
Influence of Uncontrolled Diabetes on the Kinetic Disposition, Metabolism and Pharmacokinetics-pharmacodynamics of Tramadol Enantiomers in Patients With Neuropathic Pain [NCT02246712]	Phase 4	30 participants (Actual)	Interventional	2008-06-30	Completed
Tolerability of QUTENZATM When Applied After Pre-treatment With Lidocaine or Tramadol in Subjects With Peripheral Neuropathic Pain - A Randomized, Multi-center, Assessor-blinded Study [NCT01416116]	Phase 4	122 participants (Actual)	Interventional	2011-07-06	Completed
Efficacy of Duloxetine in Conjunction With Tramadol for Chronic Cancer Pain [NCT05311774]		400 participants (Anticipated)	Interventional	2022-04-30	Not yet recruiting
Ultracet (Tramadol HCL [37.5 mg]/Acetaminophen [325 mg]) Combination Tablets in the Treatment of the Pain of Fibromyalgia [NCT00766675]	Phase 4	80 participants (Actual)	Interventional	2008-10-31	Completed
A Study of a Long-term Administration of JNS013 in Patients With Chronic Pain [NCT00736957]	Phase 3	219 participants (Actual)	Interventional	2008-05-31	Completed
Randomized Controlled Trial on Effectiveness of Ketorolac and Tramadol in Not Compound Fractures of Child [NCT00560443]	Phase 4	133 participants (Actual)	Interventional	2008-02-29	Completed
Tramadol Administered Orally to Healthy Subjects for the Improvement of Its Detection in Biological Matrices in the Context of Anti-Doping Control [NCT05925686]	Phase 1	25 participants (Actual)	Interventional	2023-06-01	Completed
Erector Spinae Plane Block for Nefrectomy [NCT04686890]		46 participants (Actual)	Interventional	2020-12-30	Completed
Analgesic Efficacy of Ropivacaine Alone or in Combination With Adjuvants on Post-operative Analgesia Following Video-Assisted Thoracoscopic Surgery (VATS) - A Randomized Controlled Trial. [NCT03809442]	Phase 4	120 participants (Anticipated)	Interventional	2019-06-25	Recruiting
Evaluation of the Effects of Subcostal Transversus Abdominis Plane Block on Subacute Pain Development Following Inguinal Herniography: a Randomized Clinical Study [NCT02914028]		2 participants (Actual)	Interventional	2016-04-30	Completed
Efficacy of Extended-release, Once Daily Tramadol for Post Operative in Ambulatory Shoulder Arthroscopy [NCT02247648]	Phase 2	100 participants (Actual)	Interventional	2013-06-30	Terminated
Ultrasound Guided Superficial Cervical Plexus Block Versus Greater Auricular Nerve Block for Tympanomastoid Surgery Pain [NCT03277599]		50 participants (Actual)	Interventional	2016-07-05	Completed
Double-blind, Randomized, Dose-ranging, Parallel-group Comparison of the Efficacy and Safety of Extended Release Tramadol Hydrochloride (Tramadol HCl ER) 100 mg, 200 mg, 300 mg, Celecoxib 200 mg and Placebo in the Treatment of Osteoarthritis of the Knee a [NCT00348452]	Phase 3	1,000 participants	Interventional	2002-09-30	Completed
A Randomised Double-blind Multicentre Equivalence Study With Active Parallel Comparator Group to Evaluate the Efficacy and Safety of Norspan® Patches Versus Tramadol in Subjects With Chronic, Moderate to Severe Osteoarthritis Pain in the Hip, Knee &/or Lu [NCT00426647]	Phase 4	120 participants (Anticipated)	Interventional	2007-02-28	Completed
Exploratory Study to Investigate the Efficacy and Safety of Recombinant Growth Hormone as Add-on Treatment in Patients With Severe Fibromialgia [NCT00497562]	Phase 2	0 participants	Interventional	2004-05-31	Completed
Butorphanol and Tramadol for Morphine PCA Pain Management After Total Hysterectomy [NCT00510666]	Phase 4	841 participants (Actual)	Interventional	2007-01-31	Completed
Randomized Clinical Trial to Evaluate the Utility of CYP2D6 Genotyping to Improve the Efficacy and Safety of Tramadol in the Treatment of Acute Postoperative Pain. [NCT05657704]	Phase 4	300 participants (Anticipated)	Interventional	2022-10-05	Recruiting
Comparison of Dorsal Penile Nerve Block With 0.33% Ropivacaine and Intravenous Tramadol for Prevention of Catheter-related Bladder Discomfort: Study Protocol for a Randomized Controlled Trial [NCT01721031]	Phase 3	58 participants (Actual)	Interventional	2013-04-01	Completed
Comparison of the Effectiveness and Safety Between Tramadol 37.5 Mg/Acetaminophen 325mg And Gabapentin for The Treatment of Painful Diabetic Neuropathy: Multicenter, Randomized, Open Comparative Study [NCT00634543]	Phase 4	162 participants (Actual)	Interventional	2006-12-31	Completed
Randomized Double Blind Study Comparing Patient Controlled Analgesia With Tramadol vs. Remifentanyl for Women Undergoing 2nd Trimester Abortions [NCT00361686]		40 participants (Anticipated)	Interventional	2006-01-31	Completed
Comparing the Efficacy of Intravenous Dexmedetomidine, Tramadol and Ketamine for Control of Post Spinal Shivering in Obstetric Patients Undergoing Lower Segment C-section [NCT05311722]	Phase 3	71 participants (Anticipated)	Interventional	2022-04-30	Not yet recruiting
Multimodal Narcotic Limited Perioperative Pain Control With Colorectal Surgery as Part of an Enhanced Recovery After Surgery Protocol: A Randomized Prospective Single- Center Trial. [NCT02958566]	Phase 4	80 participants (Anticipated)	Interventional	2017-01-31	Recruiting
Efficacy of Intravenous Ibuprofen and Paracetamol on Postoperative Pain and Tramadol Consumption in Shoulder Surgery: Prospective, Randomized, Double-Blind Clinical Trial [NCT05401916]		2 participants (Actual)	Interventional	2022-06-10	Completed
Double-Blind, Randomized,Dose-Ranging, Parallel-Group Comparison Of The Efficacy And Safety Of Extended-Release Tramadol Hydrochloride(Tramadol HCl ER)100 Mg, 200 Mg, 300 Mg, And 400 Mg With Placebo In The Treatment Of Osteoarthritis Of Knee And/Or Hip [NCT00325858]	Phase 3	1,000 participants	Interventional	2002-01-31	Completed
Tramadol iv. : Influence of Dose and Dose Intervals on Therapeutic Accuracy and Side Effects When Used for Postoperative Pain Relief in Ambulatory Surgery [NCT00333346]	Phase 2	200 participants (Anticipated)	Interventional	2006-09-30	Completed
Withdrawal Suppression Efficacy of Tramadol [NCT00142896]	Phase 2	16 participants (Actual)	Interventional	2005-02-28	Completed
Double-blind, Randomized, Dose-titration, Parallel-group Comparison of the Efficacy and Safety of Extended Release Tramadol Hydrochloride (Tramadol HCl ER) and Placebo in the Treatment of Osteoarthritis of the Knee. [NCT00348010]	Phase 3	245 participants	Interventional	2000-11-30	Completed
Pain Study to See if Ultram ER Will Provide Relief to Subjects Whose Pain is Not Well Controlled by Narcotics [NCT00505531]		7 participants (Actual)	Observational	2007-06-30	Terminated(stopped due to Not enough data to analyze the results.)
A Study to Compare the Bioavailability of Two Tramadol Hydrochloride Tablet Products (50 mg and 200 mg, Respectively) at Steady-state Under Fasting Conditions [NCT00834288]	Phase 1	26 participants (Actual)	Interventional	2003-06-30	Completed
Comparative Bioavailability Between Two Tramadol Formulations: Study of the Better Controlled Release of a New 200 mg OAD Formulation Versus Zytram® 200 mg [NCT00911742]	Phase 1	26 participants (Actual)	Interventional	2004-02-29	Completed
Efficacy and Safety of Etoricoxib-tramadol 120mg/100mg on Acute Pain After Impacted Lower Third Molar Extraction: A Double Blind Randomized Controlled Trial [NCT05995912]	Phase 2	58 participants (Actual)	Interventional	2021-09-29	Completed
A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy and Safety of ULTRACET® (Tramadol HCl/Acetaminophen) for the Treatment of Acute Low Back Pain [NCT00210561]	Phase 4	22 participants (Actual)	Interventional	2005-03-31	Terminated(stopped due to Study was stopped shortly after initiation due to change in strategic direction of the company; no safety concerns were observed that impacted this decision.)
Double-blind, Randomised, Placebo and Active Controlled, Parallel Group Study to Evaluate the Analgesic Effect of a Single Oral Administration of Four Different Combination Doses of DKP.TRIS With TRAM.HCL in Comparison With the Single Agents, on Moderate [NCT01307020]	Phase 2	745 participants (Actual)	Interventional	2011-02-28	Completed
Comparative Bioavailability Study Between Etoricoxib 90 mg and Tramadol 50 mg, Administered Individually or in Combination, Single Dose in Healthy Subjects of Both Genders Under Fasting Conditions [NCT05533073]	Phase 1	42 participants (Actual)	Interventional	2020-08-03	Completed
Effect of Perioperative Electroacupuncture With Tramadol and Ketamine on Postoperative Analgesia in Prostatectomy: a Randomized Placebo-controlled Trial [NCT01526525]	Phase 4	70 participants (Actual)	Interventional	2009-07-31	Completed
Investigation of the Efficacy of Unilateral Rhomboid Intercostal and Subserratus Plane Block Application for Postoperative Analgesia in Laparoscopic Cholecystectomy [NCT04761029]		50 participants (Actual)	Interventional	2018-01-01	Completed
Effect of a Transversus Abdominis Plane Block on Operative Wound Healing, Stress, and Immune Response After a Cesarean Delivery [NCT05840406]		120 participants (Anticipated)	Interventional	2024-04-01	Not yet recruiting
Post-Operative Pain Relief Following Insertion of Radioactive Plaque for Choroidal Melanoma: Randomised Control Trial of Tramadol Vs Ibuprofen: A Pilot Study [NCT00111046]	Phase 1/Phase 2	40 participants	Interventional	2001-02-28	Active, not recruiting
Comparative, Randomized Trial of SPI-directed Intravenous Analgesia Using Metamizole With Tramadol Versus Preemptive Wound Infiltration Using 0,2 % Ropivacaine With Fentanyl or 0,2 % Bupivacaine With Fentanyl for Lumbar Discectomy [NCT02971540]		132 participants (Actual)	Interventional	2016-02-29	Completed
Comparative Study of Analgesic Effect and Serum IL-6 With Tramadol Infiltration or Intravenous After Tonsillectomy [NCT01636700]		0 participants (Actual)	Interventional	2011-10-31	Withdrawn
A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Tramadol HCl/Acetaminophen for the Treatment of Painful Diabetic Neuropathy [NCT00210847]	Phase 3	313 participants (Actual)	Interventional	2003-12-31	Completed
The Effects of Tramadol Combined With Local Anesthesia on Pain After the Surgical Extraction of Third Molars [NCT05614440]	Early Phase 1	60 participants (Actual)	Interventional	2012-05-01	Completed
Evaluation of the Influence of Tramadol Injection Simultaneous With Sciatic Nerve Block on the Duration of Efficient Sensory Blockade in Patients Operated on for Calcaneus Fracture [NCT03477851]	Phase 4	40 participants (Actual)	Interventional	2017-06-15	Completed
A Multicenter, Randomized, Double-blind, Dose Finding, Parallel Controlled With Active Drug and Placebo, Phase II Clinical Trial to Evaluate the Efficacy and Safety of HR18042 Tablets for Postoperative Analgesia After Impacted Teeth Removal Surgery [NCT05470075]	Phase 2	180 participants (Anticipated)	Interventional	2022-08-11	Recruiting
Preemptive Oral Gabapentin Versus Tramadol on Postoperative Pain After Knee Arthroscopy Done Under Spinal Anesthesia: A Prospective Randomized Trial [NCT06112223]		50 participants (Anticipated)	Interventional	2023-11-10	Not yet recruiting
The Impact of the Single Nucleotide Polymorphisms rs6746030,rs7604448, rs10930214, s7595255 in SCN9A Gene on Postoperative Pain and Analgesic Consumption After Cesarean Section [NCT02496455]		200 participants (Actual)	Observational	2015-08-31	Completed
A Comparison of the Efficacy and Safety of Tramadol HCl/Acetaminophen Versus Hydrocodone Bitartrate/Acetaminophen Versus Placebo in Subjects With Acute Musculoskeletal Pain [NCT00236535]	Phase 3	603 participants (Actual)	Interventional	2003-12-31	Completed
A Comparison of the Efficacy and Safety of ULTRACET® (Tramadol HCl/Acetaminophen) Versus ULTRAM® (Tramadol HCl) Versus Placebo in Subjects With Pain Following Oral Surgery [NCT00236483]	Phase 4	456 participants (Actual)	Interventional	2002-11-30	Completed
A Six Week Double-Blind, Randomized, Multicenter Comparison Study of the Analgesic Effectiveness of Celecoxib 200 mg BID Compared to Tramadol Hydrochloride 50 mg QID in Subjects With Chronic Low Back Pain [NCT00290901]	Phase 4	754 participants	Interventional	2006-03-31	Completed
A Comparison of the Efficacy and Safety of ULTRACET® (Tramadol HCl/Acetaminophen) Versus Placebo for the Acute Treatment of Migraine Headache Pain [NCT00297375]	Phase 4	375 participants (Actual)	Interventional	2003-04-30	Completed
Efficacy of Tramadol Hcl in the Treatment of Renal Colic [NCT00310908]	Phase 4	100 participants (Anticipated)	Interventional	2006-09-30	Completed
Open-label Assessment of the Safety and Effectiveness of Extended Release Tramadol (Tramadol ER) in the Treatment of Chronic Non-malignant Pain. [NCT00347685]	Phase 3	650 participants	Interventional	2000-10-31	Completed
Double-blind, Randomized, Placebo-controlled, Parallel Group Comparison of the Efficacy and Safety of Extended Release Tramadol (Tramadol ER) 300 mg and 200 mg to Placebo in the Treatment of Chronic Low Back Pain [NCT00347724]	Phase 3	600 participants	Interventional	2000-11-30	Completed
The Efficacy of Pain Management Protocol for Elderly Hip Fracture Patients After Surgery: A Prospective Cohort Study [NCT01630343]	Phase 2	400 participants (Actual)	Interventional	2010-01-31	Completed
"NSAIDs vs. Opiates: Which is More Effective in Managing Pain in Mild to Moderate Acute Pancreatitis? A Randomized Controlled Trial" [NCT05756504]	Early Phase 1	130 participants (Anticipated)	Interventional	2023-02-22	Recruiting
A Randomized, Double-blind, Active-controlled, Parallel, Multicenter Phase 3 Study of Tramadol Hydrochloride/Acetaminophen SR Tab. & Tramadol Hydrochloride/Acetaminophen Tab. in Low Back Pain Patients [NCT01776515]	Phase 1	0 participants	Interventional	2012-01-31	Completed
A Single Dose, Open-Label, Randomized, Two-Way Crossover Pivotal Study to Assess the Bioequivalence of a New ULTRACET ER Tablet With Respect to a Marketed ULTRACET ER Tablet Under Fasted Condition [NCT01778075]	Phase 1	56 participants (Actual)	Interventional	2012-12-31	Completed
Effect of Early Analgesic Treatment on Opioid Consumption [NCT03243006]		1,500 participants (Actual)	Interventional	2016-01-01	Completed
The Effects of Fascia Iliaca Compartment Block on Hip Fracture Patients [NCT04837924]	Phase 4	80 participants (Actual)	Interventional	2021-04-21	Completed
A Comparison of Postoperative Tramadol Versus Acetaminophen With Codeine in Children Undergoing Tonsillectomy [NCT01267136]	Phase 4	84 participants (Actual)	Interventional	2011-01-31	Completed
ZIH Study : Comparison of Oral Zaldiar (Combination of Paracetamol and Tramadol) With Intravenous Paracetamol and Tramadol for Postoperative Analgesia After Inguinal Hernia Repair [NCT02389361]	Phase 4	51 participants (Actual)	Interventional	2011-04-30	Completed
A Randomized Controlled Trial on the Efficacy, Safety and Quality of Life Effects of Add-on Tramadol/Paracetamol Combination in Chronic Osteoarthritis [NCT01728246]	Phase 4	473 participants (Actual)	Interventional	2007-10-31	Completed
Metabolites of Tramadol in the Postoperative Surgical Patients Admitted in the ICU [NCT04004481]		50 participants (Actual)	Observational	2019-01-25	Completed
Oral Tramadol Versus Oral Dexketoprofen for Reducing Pain During Office Hysteroscopy in Post Menopausal Women [NCT03585036]	Phase 3	210 participants (Anticipated)	Interventional	2018-07-31	Not yet recruiting
A Randomized, Double-blind, Active-controlled, Parallel, Multicenter Phase 3 Study of Tramadol Hydrochloride/Acetaminophen SR Tab. & Tramadol Hydrochloride/Acetaminophen Tab. in Acute Toothache Patients After Teeth Extraction Surgery [NCT01920386]	Phase 3	240 participants (Actual)	Interventional	2013-06-30	Completed
A Randomized, Double-Blind, Multicenter, Placebo- and Active Comparator-Controlled Study to Evaluate Efficacy and Safety of MR308 in the Treatment of Acute Pain After Third Molar Tooth Extraction (STARDOM1). [NCT02982161]	Phase 3	818 participants (Actual)	Interventional	2016-12-28	Completed
Medications Development for Drug Abuse Disorders [NCT01188421]	Phase 1/Phase 2	106 participants (Actual)	Interventional	2010-10-31	Completed
Does Duloxetine Reduce Chronic Pain After Total Knee Arthroplasty? [NCT02307305]	Phase 2	168 participants (Anticipated)	Interventional	2014-08-31	Recruiting
Role of Prophylactic Metoclopramide With Tramadol in Trauma Patients: A Randomised, Double Blind Placebo Controlled Trial [NCT03383315]	Phase 2	191 participants (Actual)	Interventional	2017-07-01	Completed
Efficacy of Extended Release Tramadol for Treating Prescription Opioid Withdrawal [NCT00980044]	Phase 2/Phase 3	53 participants (Actual)	Interventional	2009-10-31	Completed
Effect of Preoperative Oral Tramadol on the Anaesthetic Efficacy of Inferior Alveolar Nerve Block in Patients With Symptomatic Irreversible Pulpitis: A Prospective, Randomized, Double-blind, Controlled Study [NCT04961268]		250 participants (Actual)	Interventional	2020-06-01	Completed
Project 1 Aim 2, Adaptations of the Brain in Chronic Pain With Opioid Exposure [NCT05463367]	Phase 2	80 participants (Anticipated)	Interventional	2021-01-01	Recruiting
Confirmatory Study of Efficacy and Safety of the Pregabalin/Tramadol Combination Versus Pregabalin in the Management of Acute Pain of Neuropathic Origin. [NCT05324059]	Phase 3	110 participants (Actual)	Interventional	2022-07-11	Completed
A Double-Blind, Placebo-Controlled, Flexible-Dose Pilot Clinical Trial of Once-Daily Extended-Release Tramadol for the Treatment of PTSD [NCT01517711]	Phase 4	40 participants (Actual)	Interventional	2011-09-30	Completed
The Effect of Intraoperative Tramadol on Postoperative Opioid Requirements After Laparoscopic Sleeve Gastrectomy for Morbid Obese Patients (A Retrospective Multicentric Cohort Study) [NCT05696886]		400 participants (Actual)	Interventional	2021-01-01	Completed
"A Randomized, Open-label, Multiple-dose, Parallel Study to Compare the Pharmacokinetics and to Evaluate Drug-Drug Interaction of CG100650 in Healthy Volunteers" [NCT03775629]	Phase 1	41 participants (Actual)	Interventional	2018-12-01	Completed
Comparison of Preoperative Analgesics on the Efficacy of Inferior Alveolar Nerve Block on Patients With Symptomatic Irreversible Pulpitis: a Double Blinded, Randomized Controlled Trial. [NCT05488925]	Phase 4	120 participants (Actual)	Interventional	2021-06-21	Completed
Intraoperative Use of Dexketoprofen Trometamol, Tramadol Hcl, Pethidine Hcl and Their Combinations for Postoperative Pain Management in Laparoscopic Nissen Fundoplication [NCT01558622]	Phase 4	72 participants (Anticipated)	Interventional	2012-03-31	Active, not recruiting
Comparison of Postoperative Analgesic Effects of Transversus Abdominis Plane Block and Quadratus Lumborum Block Type 2 [NCT03126084]	Phase 4	90 participants (Actual)	Interventional	2017-05-02	Completed
A Comparison of Tramadol/Acetaminophen Tablets Maintenance Versus NSAID Maintenance After Tramadol/Acetaminophen and NSAID Combination Therapy in Knee Osteoarthritis Patients: Multicenter, Randomized, Open Comparative Study [NCT00635349]	Phase 4	143 participants (Actual)	Interventional	2007-05-31	Completed
Randomized, Double-blind, Placebo-controlled, Parallel Arm Group Study Evaluating Analgesic Efficacy and Safety of Dexketoprofen Trometamol and Tramadol Hydrochloride on Moderate to Severe Acute Pain in Patients With Acute Low Back Pain [NCT05170841]	Phase 4	544 participants (Actual)	Interventional	2020-09-17	Completed
The Clinical Efficacy and Safety Study of Tramadol Hydrochloride - Paracetamol Tablets in the Treatment of Moderate to Severe Acute Neck-shoulder Pain and Low Back Pain in Orthopaedics Outpatient or Emergency Setting [NCT01843660]	Phase 4	1,059 participants (Actual)	Interventional	2007-09-30	Completed
A Randomized, Double-blind, Placebo and Active-controlled, Parallel-group Study to Evaluate the Analgesic Efficacy and Safety of Dexketoprofen Trometamol and Tramadol Hydrochloride Oral Fixed Combination on Moderate to Severe Acute Pain Following Abdomina [NCT01904149]	Phase 3	606 participants (Actual)	Interventional	2013-05-31	Completed
Local Wound Anesthesia in Spine Surgery - a Randomized Double Blind Controlled Trial [NCT05693454]		150 participants (Actual)	Interventional	2021-11-01	Completed
MAST Trial: Multi-modal Analgesic Strategies in Trauma [NCT03472469]	Phase 4	1,561 participants (Actual)	Interventional	2018-04-02	Completed
Effect of Single Dose of Tramadol on Extubation Response and Quality of Emergence(Cough and Nausea Vomiting) Following Supratentorial Intracranial Surgery [NCT02964416]	Phase 4	80 participants (Actual)	Interventional	2016-03-31	Completed
A Randomized, Double-blind, Active- (Tramadol and Celecoxib) and Placebo-controlled, Parallel Groups, Phase 3 Clinical Trial to Establish the Efficacy of Co-crystal E-58425 for the Management of Moderate to Severe Post-surgical Pain After Bunionectomy. [NCT03108482]	Phase 3	637 participants (Actual)	Interventional	2017-03-14	Completed
Comparison of Efficacy of Transversus Abdominis Plane Block and Ilioinguinal Nerve Block for Postoperative Pain Management in Patients Undergoing Inguinal Herniorraphy With Spinal Anesthesia [NCT02375100]		90 participants (Actual)	Interventional	2015-02-28	Completed
The Effect of Dexamethasone Versus Local Infiltration Technique on Postoperative Nausea and Vomiting After Tonsillectomy in Children: A Randomized Double-blind Clinical Trial [NCT02355678]		129 participants (Actual)	Interventional	2015-01-31	Completed
Sublingual Analgesia for Acute Abdominal Pain in Children. Ketorolac Versus Tramadol Versus Paracetamol, a Randomized, Control Trial [NCT02465255]	Phase 3	210 participants (Actual)	Interventional	2015-03-31	Completed
Diclofenac Premedication, as the Effect of Preemptive Analgesia After Post-thoracotomy Chest and Shoulder Pain, as Well as the Changes of the Postoperative Breathing Function Values, a Randomized, Controlled, Prospective Trial [NCT02445599]	Phase 4	3 participants (Actual)	Interventional	2014-04-30	Completed
Tramadol Versus Diclofenac for Reducing Pain Before Outpatient Hysteroscopy in Post Menopausal Women: A Randomized Double Blind Placebo Controlled Trial [NCT02425709]	Phase 3	210 participants (Anticipated)	Interventional	2015-04-30	Recruiting
Comparison of the Analgesic Efficacy of Lidocaine Spray Versus Tramadol and Fentanyl for Pain Control in Rib Fractures: A Prospective, Randomized, Controlled and Open-label Study [NCT05500677]	Phase 4	48 participants (Actual)	Interventional	2021-06-01	Completed
To Compare the Efficacy and Patients' Satisfaction for the Treatment of Post Cesarean Pain of Two Protocols: Oral Medications in Fixed Time Interval Administration Versus Spinal Morphine [NCT02440399]		200 participants (Actual)	Interventional	2015-07-31	Completed
Tramadol Versus Diclofenac for Prevention of Pain in Operative Outpatient Hysteroscopy: A Randomized Double Blind Placebo Controlled Trial [NCT02428777]	Phase 3	210 participants (Anticipated)	Interventional	2015-04-30	Recruiting
Fast-release Orodispersible Tramadol as Analgesia in Termination of Pregnancy by Vacuum Aspiration. [NCT02416141]	Phase 4	128 participants (Anticipated)	Interventional	2015-04-30	Not yet recruiting
Tramadol Versus Diclofenac for Reducing Pain Associated With Outpatient Hysteroscopy: A Randomized Double Blind Placebo-Controlled Trial [NCT02419651]	Phase 3	210 participants (Anticipated)	Interventional	2015-04-30	Recruiting
Comparing Post-operative Analgesic Effectiveness of Wound Infiltration Using Bupivacaine, Tramadol, and Tramadol Plus Bupivacaine in Patients Undergoing Elective Cesarean Section Under Spinal Anesthesia at Dessie Comprehensive Specialized Hospital, Ethiop [NCT06076707]	Phase 4	163 participants (Anticipated)	Interventional	2023-11-30	Not yet recruiting
Preemptive Intravenous Paracetamol Plus Tramadol Versus Preemptive Intravenous Fentanyl in Day Case Surgeries [NCT05990686]		132 participants (Anticipated)	Observational	2023-01-10	Recruiting
Comparative, Randomized, Double-Blind, Single-Dose, 2-way Crossover Study to Evaluate the Pharmacokinetics and Analgesic Effect of Labopharm Tramadol Contramid® OAD 200 mg Tablets or Placebo in Healthy Young and Elderly Adult Volunteers [NCT02329561]	Phase 1	35 participants (Actual)	Interventional	2007-01-31	Completed
Intraoperative Lidocaine Infusion vs. Esmolol Infusion for Postoperative Analgesia in Laparoscopic Cholecystectomy: a Randomized Clinical Trial [NCT02327923]	Phase 4	90 participants (Actual)	Interventional	2015-01-31	Completed
Comparison of Effect of Peritonsillar Infiltration of Ketamine and Tramadol on Pediatric Posttonsillectomy Pain: A Double-blinded Randomized Placebo-controlled Clinical Trial [NCT03067103]	Phase 4	108 participants (Anticipated)	Interventional	2017-07-01	Not yet recruiting
a Multicenter, Double-blind, Randomized, Active Drug Control, Parallel Design Phase 3 Clinical Trial to Evaluate the Efficacy and Safety of YYC301 in Patients With Osteoarthritis of the Knee Joint [NCT05362851]	Phase 3	692 participants (Anticipated)	Interventional	2021-11-11	Recruiting
Evaluation of the Effect of Serratus Anterior Plane Block for Pain Treatment After Video-Assisted Thoracoscopic Surgery [NCT03217292]		40 participants (Actual)	Interventional	2016-07-01	Completed
A Comparison of Non-Surgical Treatment Methods for Patients With Lumbar Spinal Stenosis [NCT01943435]		259 participants (Actual)	Interventional	2013-11-20	Completed
[NCT00834808]	Phase 1	27 participants (Actual)	Interventional	2002-11-30	Completed
A PHASE 3, RANDOMIZED, DOUBLE BLIND, PLACEBO AND ACTIVE-CONTROLLED, MULTICENTER, PARALLEL-GROUP STUDY OF THE ANALGESIC EFFICACY AND SAFETY OF TANEZUMAB IN ADULT SUBJECTS WITH CHRONIC LOW BACK PAIN [NCT02528253]	Phase 3	1,832 participants (Actual)	Interventional	2015-08-18	Completed
A Single-dose, Randomized, Double-blind, Placebo- and Active-controlled Crossover Trial to Evaluate the Abuse Potential of Two Doses of Cebranopadol in Adult Nondependent Recreational Opioid Users [NCT05256108]	Phase 1	38 participants (Actual)	Interventional	2022-03-28	Completed
Tramadol for Labor Analgesia in Low Risk Women: A Placebo Controlled Randomized Trial [NCT02999594]	Phase 2	86 participants (Anticipated)	Interventional	2016-12-31	Not yet recruiting
A Randomized, Double-blind, Placebo and Active-controlled, Parallel-group Study to Evaluate the Analgesic Efficacy and Safety of Dexketoprofen Trometamol and Tramadol Hydrochloride Oral Fixed Combination on Moderate to Severe Acute Pain After Elective Uni [NCT01902134]	Phase 3	641 participants (Actual)	Interventional	2013-04-30	Completed
Comparative Study of Conventional and Topical Heparin Treatments in Second Degree Burn Patients for Burn Analgesia and Duration of Wound Healing [NCT02497326]		36 participants (Anticipated)	Interventional	2015-04-30	Recruiting
The Effect of Gabapentin Used as a Preemptive to the Emergence and Development Chronic Neuropathic Pain in Patients After Spinal Cord Trauma [NCT03255330]	Phase 3	0 participants (Actual)	Interventional	2017-10-31	Withdrawn(stopped due to no participant enrolled)
The Efficiency of Periarticular Multimodal Drug Injection in Pain Management Following Primary Unilateral Total Knee Arthroplasty: a Randomized Controlled Trial [NCT06112548]		80 participants (Anticipated)	Interventional	2023-11-01	Not yet recruiting
Phase 3 Double Blind Randomized Study Comparing Drug Treatment (Tramadol Versus Placebo) and Behavioral Health Treatments (Cognitive Behavioral Therapy Versus Health Education) for Patients With Fibromyalgia [NCT01598753]	Phase 3	134 participants (Actual)	Interventional	2012-05-31	Completed
Intrathecal Morphine Compared to Intravenous Tramadol and Transversus Abdominal Plane Block for Catheter Related Bladder Discomfort Syndrome [NCT04814745]		33 participants (Actual)	Interventional	2020-07-07	Completed
The Use of Buprenorphine Transdermal Patches Improves Post-Operative Pain Management in Arthroscopic Rotator Cuff Repair? [NCT03380533]	Phase 2/Phase 3	50 participants (Actual)	Interventional	2016-09-22	Completed
Evaluation of the Efficacy of M-TAPA and EXORA Block Application for Analgesia After Laparoscopic Cholecystectomy; Prospective, Single-blind, Observational Study [NCT06008002]		90 participants (Anticipated)	Interventional	2023-08-25	Not yet recruiting
Effect of Tramadol in Prevention of Postpartum Depression [NCT03309163]	Phase 4	1,230 participants (Actual)	Interventional	2017-10-09	Completed
Opioid Induced Gait Variability [NCT03121547]	Phase 1/Phase 2	24 participants (Actual)	Interventional	2015-05-19	Completed
A Multicenter, Phase IV, Interventional Study to Compare the Efficacy and Safety of NORSPAN to Tramadol/Acetaminophen in Patients With Prolonged Postoperative Pain After Spinal Surgery (PASSION) [NCT01983111]	Phase 4	136 participants (Actual)	Interventional	2013-10-31	Completed
Comparison Between Ketamine and Tramadol for Pain Management After Major Upper Abdominal Surgery [NCT02499341]		42 participants (Actual)	Interventional	2011-07-31	Completed
Management of Postsurgical Pain After Cardiac Operations: Comparison of Tapentadol and Tramadol Analgesia [NCT04718116]		90 participants (Anticipated)	Interventional	2022-11-01	Recruiting
Comparative Study of Ultrasound-guided Paravertebral Block Versus Intravenous Tramadol for Postoperative Pain Control in Percutaneous Nephrolithotomy [NCT02412930]	Phase 4	53 participants (Actual)	Interventional	2012-03-31	Completed
Opioid-Free Pain Control Regiment Following Robotic Radical Prostatectomy: A Randomized Controlled Trial [NCT04939987]	Phase 2/Phase 3	0 participants (Actual)	Interventional	2022-08-31	Withdrawn(stopped due to PI left institution and study was not transferred to new PI)
A Randomized, Active-Controlled, Parallel Group, Double-Blind Study to Compare the Efficacy and Safety of Tramadol HCl/Acetaminophen ER and IR in Subjects Who Complain of Moderate to Severe Postoperative Pain [NCT01814878]	Phase 3	320 participants (Actual)	Interventional	2009-11-30	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

Trial	Outcome
NCT00499746 (8) [back to overview]	Discrimination Effects Assessed by Discrete Choice
NCT00499746 (8) [back to overview]	Physiological Effects Assessed by Peak Change From Baseline Pupil Diameter
NCT00499746 (8) [back to overview]	Peak Change From Baseline Stimulant Effects Assessed by the Visual Analog Scale (VAS)
NCT00499746 (8) [back to overview]	Acquisition of Discrimination Assessed by Accuracy of the Discrimination Test
NCT00499746 (8) [back to overview]	Peak Change From Baseline Opioid Agonist Effects Assessed by the Visual Analog Scale (VAS)
NCT00499746 (8) [back to overview]	Physiologic Effects Assessed by the Pharmacological Class Questionnaire
NCT00499746 (8) [back to overview]	Discrimination Effects Assessed by Point Distribution
NCT00499746 (8) [back to overview]	Discrimination Effects Assessed by Operant Responses
NCT00610155 (5) [back to overview]	Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa)
NCT00610155 (5) [back to overview]	Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc)
NCT00610155 (5) [back to overview]	Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH)
NCT00610155 (5) [back to overview]	Present Pain Intensity Score (PPIS)
NCT00610155 (5) [back to overview]	Daily Pain Score
NCT00634543 (6) [back to overview]	Change From Baseline in Short Form-36 (SF-36) Score at Day 43
NCT00634543 (6) [back to overview]	Percentage of Participants With Pain Relief
NCT00634543 (6) [back to overview]	Overall Assessment of Study Medication by Participants
NCT00634543 (6) [back to overview]	Overall Assessment of Study Medication by Investigator
NCT00634543 (6) [back to overview]	Change From Baseline in Pain Intensity Score at Day 43
NCT00634543 (6) [back to overview]	Change From Baseline in Brief Pain Inventory (BPI) Score at Day 43
NCT00635349 (7) [back to overview]	Change From Day 29 in Pain Intensity Score at Day 85
NCT00635349 (7) [back to overview]	Number of Participants With Pain Relief
NCT00635349 (7) [back to overview]	Number of Participants With Overall Assessment on Study Drug by Participants
NCT00635349 (7) [back to overview]	Number of Participants With Overall Assessment on Study Drug by Investigator
NCT00635349 (7) [back to overview]	Number of Participants With Categorical Tenderness
NCT00635349 (7) [back to overview]	Number of Participants With Categorical Swelling
NCT00635349 (7) [back to overview]	Change From Day 29 in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Total Score at Day 85
NCT00662558 (14) [back to overview]	Patient's Satisfaction Questionnaire (With Walking and Bending Ability Scale)
NCT00662558 (14) [back to overview]	Patient's Satisfaction Questionnaire (With Pain Relief Scale)
NCT00662558 (14) [back to overview]	Patient's Global Evaluation of Study Medication
NCT00662558 (14) [back to overview]	Patient's Global Assessment of Disease Activity
NCT00662558 (14) [back to overview]	Number of Subjects With Change From Baseline in MOS Optimal Sleep Scale Scores
NCT00662558 (14) [back to overview]	Chronic Low Back Pain Responders Based on VAS, Patient's Global, and RMDQ
NCT00662558 (14) [back to overview]	Change From Baseline in Work Limitations Questionnaire (WLQ)
NCT00662558 (14) [back to overview]	Change From Baseline in Modified Brief Pain Inventory (m-BPI-sf)
NCT00662558 (14) [back to overview]	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale
NCT00662558 (14) [back to overview]	Change From Baseline in Severity of Low Back Pain as Measured by Visual Analogue Scale (VAS)
NCT00662558 (14) [back to overview]	Physician's Global Assessment of Disease Activity
NCT00662558 (14) [back to overview]	Change From Baseline in Roland-Morris Disability Questionnaire (RMDQ) Total Score
NCT00662558 (14) [back to overview]	Treatment Responders Based on the Numerical Rating Scale-Pain (NRS-Pain)
NCT00662558 (14) [back to overview]	Change From Baseline in Severity of Chronic Low Back Pain as Measured by NRS-Pain
NCT00733421 (9) [back to overview]	Gastro-intestinal Symptoms
NCT00733421 (9) [back to overview]	Wound Healing
NCT00733421 (9) [back to overview]	Dizziness/Sleepiness
NCT00733421 (9) [back to overview]	Compliance to Base Medication
NCT00733421 (9) [back to overview]	Satisfaction With Pain Medication
NCT00733421 (9) [back to overview]	Patient Assessed Overall Satisfaction With Surgery/Outcome
NCT00733421 (9) [back to overview]	Summary of Pain Scores, Day 1-7 of Visual Analogue Scale Grading of Pain
NCT00733421 (9) [back to overview]	Patient Assessed Quality of Life
NCT00733421 (9) [back to overview]	Number of Patients Requiring Rescue Medication
NCT00736853 (23) [back to overview]	Pain Intensity Difference and Pain Relief Scores (PRID) During the Open-Label Period
NCT00736853 (23) [back to overview]	Sum of Pain Relief Combined With Pain Intensity Difference (SPRID) Score During the Open-Label Period
NCT00736853 (23) [back to overview]	Total Pain Relief (TOTPAR) Score During the Double-Blind Period
NCT00736853 (23) [back to overview]	Total Pain Relief (TOTPAR) Score During the Open-Label Period
NCT00736853 (23) [back to overview]	Sum of Pain Intensity Difference (SPID) Score During the Double-Blind Period
NCT00736853 (23) [back to overview]	Change From Baseline in Roland Morris Disability Questionnaire (RDQ) Total Score at Day 14 of Open-Label Period
NCT00736853 (23) [back to overview]	Change From Baseline in RDQ Total Score at Day 28 of Double-Blind Period
NCT00736853 (23) [back to overview]	Number of Participants With Insufficient Pain Relief After the Start of Double-Blind Period
NCT00736853 (23) [back to overview]	Sum of Pain Intensity Difference (SPID) Score During the Open-Label Period
NCT00736853 (23) [back to overview]	Sum of Pain Relief Combined With Pain Intensity Difference (SPRID) Score During the Double-Blind Period
NCT00736853 (23) [back to overview]	Pain Intensity Difference and Pain Relief Scores (PRID) During the Double-Blind Period
NCT00736853 (23) [back to overview]	Mean PID During the Double-Blind Period
NCT00736853 (23) [back to overview]	Mean PI Score During Double-Blind Period
NCT00736853 (23) [back to overview]	Mean PAR Score During the Double-Blind Period
NCT00736853 (23) [back to overview]	Mean Pain Relief (PAR) Score During the Open-Label Period
NCT00736853 (23) [back to overview]	Mean Pain Intensity Difference (PID) During the Open-Label Period
NCT00736853 (23) [back to overview]	Mean Pain Intensity (PI) Score During Open-Label Period
NCT00736853 (23) [back to overview]	Change in the VAS24 Value From the Baseline at the Final Time Point of the Double-Blind Period
NCT00736853 (23) [back to overview]	Change in the Visual Analog Scale for the Last 24 Hours (VAS24) Value at the Start of the Double-Blind Period From the Baseline Value at the Start of the Open-Label Period
NCT00736853 (23) [back to overview]	Change From Baseline in WOMAC Questionnaire Score at Day 28 of Double-Blind Period
NCT00736853 (23) [back to overview]	Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Questionnaire Score at Day 14 of Open-Label Period
NCT00736853 (23) [back to overview]	Change From Baseline in Short Form-36 (SF-36) Score at Day 14 of Open-Label Period
NCT00736853 (23) [back to overview]	Change From Baseline in SF-36 at Day 28 of Double-Blind Period
NCT00736957 (7) [back to overview]	Change From Baseline in Short Form-36 (SF-36) Score
NCT00736957 (7) [back to overview]	Change From Baseline in VAS24 Score at Week 52
NCT00736957 (7) [back to overview]	Change From Baseline in Visual Analogue Scale (VAS24) Score at Week 4
NCT00736957 (7) [back to overview]	Number of Participants With Improvement From Baseline in VAS24 Score
NCT00736957 (7) [back to overview]	Pain Intensity Difference (PID) at Week 4
NCT00736957 (7) [back to overview]	Pain Relief (PAR) Score at Week 4
NCT00736957 (7) [back to overview]	Pain Relief Combined With Pain Intensity Difference (PRID) at Week 4
NCT00737048 (12) [back to overview]	Number of Participants Treated With a Relief Analgesic
NCT00737048 (12) [back to overview]	Sum of Pain Intensity Difference (SPID)
NCT00737048 (12) [back to overview]	Sum of Pain Relief Combined With Pain Intensity Difference (SPRID)
NCT00737048 (12) [back to overview]	Total Pain Relief Based on Numerical Rating Scale (NRS) Score
NCT00737048 (12) [back to overview]	Change From Baseline in Visual Analog Scale (VAS) Score at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment
NCT00737048 (12) [back to overview]	Mean Change Over Time for Pain Relief (PAR) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment
NCT00737048 (12) [back to overview]	Mean Change Over Time for Pain Relief Combined With Pain Intensity Difference (PRID) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment
NCT00737048 (12) [back to overview]	Percentage of Participants With Treatment Response Based on Evaluation Criteria for Efficacy of Analgesics in Post-Tooth-Extraction Pain
NCT00737048 (12) [back to overview]	Time to Reach the Onset of Drug Efficacy and Time to Recurrence of Pain After the Onset of Drug Efficacy
NCT00737048 (12) [back to overview]	Total Pain Relief Based on Numerical Rating Scale (NRS) Score Every 4 Hours up to 8 Hours
NCT00737048 (12) [back to overview]	Percentage of Participants With Categorical Score for Patient Impressions
NCT00737048 (12) [back to overview]	Mean Change Over Time for Pain Intensity Difference (PID) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-Administration of Study Treatment
NCT00766675 (10) [back to overview]	Number of Participants With Physician Global Assessment
NCT00766675 (10) [back to overview]	Number of Participants With Subject's Global Assessment
NCT00766675 (10) [back to overview]	Sleep Questionnaire: Number of Hours to Fall Asleep and Participant Slept
NCT00766675 (10) [back to overview]	Participant Assessment Sleep Questionnaire Score
NCT00766675 (10) [back to overview]	Total Fibromyalgia Impact Questionnaire (FIQ) Score
NCT00766675 (10) [back to overview]	Tender-Point Evaluation/ Myalgic Score
NCT00766675 (10) [back to overview]	Pain Visual Analog Scale Score at Day 14
NCT00766675 (10) [back to overview]	Pain Visual Analog Scale Score at Day 28
NCT00766675 (10) [back to overview]	Pain Visual Analog Scale Score at Day 56
NCT00766675 (10) [back to overview]	Number of Participants With Categorical Scores on Pain Relief Rating Scale
NCT00832416 (8) [back to overview]	Percentage of Participants Who Dropped Out From Trial by Dropout Reason
NCT00832416 (8) [back to overview]	Percentage Difference Between WOMAC Pain Subscale Score From Baseline to the End of the Study (Week 12)
NCT00832416 (8) [back to overview]	Percentage Difference Between WOMAC Physical Function Subscale Score From Baseline to the End of the Study (Week 12)
NCT00832416 (8) [back to overview]	Percentage Difference in WOMAC Physical Function Subscale Score From Baseline to Intervening Visits (Visits 2-4)
NCT00832416 (8) [back to overview]	Investigator Global Rating of Pain Relief
NCT00832416 (8) [back to overview]	Multiple Dose Effect Using 24-hour VAS Pain Questionnaire
NCT00832416 (8) [back to overview]	Patient Global Rating of Pain for the Study Period (12 Weeks)
NCT00832416 (8) [back to overview]	Percentage Difference in WOMAC Pain Subscale Score From Baseline to Intervening Visits (Visits 2-4)
NCT00833794 (10) [back to overview]	Pain Intensity Score Stratified by Dose, at the End of the Study (Week 12 or Time of Discontinuation)
NCT00833794 (10) [back to overview]	WOMAC Pain Subscale Score at the End of the Study (Week 12 or Time of Discontinuation)
NCT00833794 (10) [back to overview]	Patient Global Impression of Change at the End of the Study (Week 12 or Time of Discontinuation)
NCT00833794 (10) [back to overview]	Physician Global Impression of Change at the End of the Study (Week 12 or Time of Discontinuation)
NCT00833794 (10) [back to overview]	Time to Response
NCT00833794 (10) [back to overview]	WOMAC Physical Function Subscale Score at the End of the Study (Week 12 or Time of Discontinuation)
NCT00833794 (10) [back to overview]	Discontinuation Due to Adverse Events
NCT00833794 (10) [back to overview]	Discontinuation Due to Lack of Efficacy
NCT00833794 (10) [back to overview]	Pain Intensity Score (11-point PINRS) After 6 Weeks of Maintenance Treatment
NCT00833794 (10) [back to overview]	Pain Intensity Score as Measured by the 11-point Pain Intensity-Numerical Rating Scale Score at the End of the Study (Week 12 or Time of Discontinuation)
NCT00833911 (1) [back to overview]	Number of Patients Having Experienced an Adverse Event During the 6-12 Month Open-Label Safety Participation
NCT00834288 (8) [back to overview]	Area Under the Plasma Concentration Versus Time Data Pairs at Steady State (AUCss)
NCT00834288 (8) [back to overview]	Percentage Swing
NCT00834288 (8) [back to overview]	Plateau Time (T75%Cmax)
NCT00834288 (8) [back to overview]	Time to Peak Exposure (Tmax)
NCT00834288 (8) [back to overview]	Half-value Duration (HVD)
NCT00834288 (8) [back to overview]	Maximum Plasma Concentration at Steady State(Cmax,ss)
NCT00834288 (8) [back to overview]	Minimum Plasma Concentration at Steady State(Cmin,ss)
NCT00834288 (8) [back to overview]	Percentage Peak-trough Fluctuation (% PTF)
NCT00834366 (5) [back to overview]	t1/2
NCT00834366 (5) [back to overview]	Tmax
NCT00834366 (5) [back to overview]	AUC(0-Inf)
NCT00834366 (5) [back to overview]	AUC(0-t)
NCT00834366 (5) [back to overview]	Cmax
NCT00834808 (5) [back to overview]	Tmax
NCT00834808 (5) [back to overview]	AUC(0-t)
NCT00834808 (5) [back to overview]	AUC(0-inf)
NCT00834808 (5) [back to overview]	t1/2
NCT00834808 (5) [back to overview]	Cmax
NCT00834912 (5) [back to overview]	AUC(0-t)
NCT00834912 (5) [back to overview]	Cmax
NCT00834912 (5) [back to overview]	Tmax
NCT00834912 (5) [back to overview]	AUC(0-∞)
NCT00834912 (5) [back to overview]	t1/2
NCT00852917 (8) [back to overview]	Percentage Difference Between WOMAC Pain Subscale Score From Baseline to the End of the Study (Week 12)
NCT00852917 (8) [back to overview]	Percentage Difference Between WOMAC Physical Function Subscale Score From Baseline to the End of the Study (Week 12)
NCT00852917 (8) [back to overview]	Dropout Rate
NCT00852917 (8) [back to overview]	Investigator Global Rating of Pain Relief
NCT00852917 (8) [back to overview]	Multiple Dose Effect Using 24-hour VAS Pain Questionnaire
NCT00852917 (8) [back to overview]	Patient Global Rating of Pain for the Study Period (12 Weeks)
NCT00852917 (8) [back to overview]	Percentage Change in WOMAC Pain Subscale Score From Baseline to Intervening Visits (Visits 2-4)
NCT00852917 (8) [back to overview]	Percentage Change in WOMAC Physical Function Subscale Score From Baseline to Intervening Visits (Visits 2-4)
NCT00911742 (5) [back to overview]	AUC (0-∞)
NCT00911742 (5) [back to overview]	Cmax
NCT00911742 (5) [back to overview]	AUC(0-t)
NCT00911742 (5) [back to overview]	Tmax
NCT00911742 (5) [back to overview]	t1/2
NCT00912015 (1) [back to overview]	Adverse Events: 12-months Safety Population
NCT00950651 (21) [back to overview]	Patient Diary: Stiffness (Between Visit Means) at Week 12
NCT00950651 (21) [back to overview]	Percentage of Change From Baseline in Average Pain Within Last 24 Hours at Week 12
NCT00950651 (21) [back to overview]	Percentage of Change From Baseline in Current Pain at Week 12
NCT00950651 (21) [back to overview]	Percentage of Change From Baseline in Least Pain Within Last 24 Hours at Week 12
NCT00950651 (21) [back to overview]	Percentage of Change From Baseline in Walking Time for 15 Meters at Week 12
NCT00950651 (21) [back to overview]	Percentage of Change From Baseline in WOMAC Pain Subscale Score at Week 12
NCT00950651 (21) [back to overview]	Percentage of Change From Baseline in WOMAC Physical Function Subscale Score at Week 12
NCT00950651 (21) [back to overview]	Percentage of Change From Baseline in WOMAC Stiffness Subscale Score at Week 12
NCT00950651 (21) [back to overview]	Percentage of Change From Baseline in WOMAC Total Score at Week 12
NCT00950651 (21) [back to overview]	Percentage of Change From Baseline in Worst Pain Within Last 24 Hours at Week 12
NCT00950651 (21) [back to overview]	Arthritis Pain at the End of Dosing Interval (24-hour Efficacy)
NCT00950651 (21) [back to overview]	Patient Global Assessment: Current Interfering Side Effects Versus Pain Relief During Previous Tramadol Treatment at Week 12
NCT00950651 (21) [back to overview]	Patient Global Assessment: Current Pain Relief Versus Pain Relief During Previous Tramadol Treatment at Week 12
NCT00950651 (21) [back to overview]	Patient Global Assessment: Side Effects Interfering With Day to Day Activities at Week 12
NCT00950651 (21) [back to overview]	Patient Global Rating of Pain Relief at Week 12
NCT00950651 (21) [back to overview]	Physician Overall Rating: Effectiveness of Pain Control 24 Hours After the Most Recent Dose of Tramadol at Week 12
NCT00950651 (21) [back to overview]	Physician Overall Rating: Overall Assessment at Week 12
NCT00950651 (21) [back to overview]	Patient Diary: Pain (Between Visit Means) at Week 12
NCT00950651 (21) [back to overview]	Patient Diary: Ability Getting Things Done (Between Visit Means) at Week 12
NCT00950651 (21) [back to overview]	Patient Diary: Difficulty With Stairs (Between Visit Means) at Week 12
NCT00950651 (21) [back to overview]	Patient Diary: Difficulty With Walking (Between Visit Means) at Week 12
NCT00952068 (5) [back to overview]	Plasma Levels of Tramadol at 0 Hour (Baseline), Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post-dose
NCT00952068 (5) [back to overview]	Patient Rating of Pain Relief at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose
NCT00952068 (5) [back to overview]	Time to Onset of Perceptible Pain Relief
NCT00952068 (5) [back to overview]	Number of Participants With Adverse Events
NCT00952068 (5) [back to overview]	Patient Rating of Pain Intensity at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose
NCT00980044 (4) [back to overview]	Total Number of Breakthrough Withdrawal Medication Doses Taken Week 2
NCT00980044 (4) [back to overview]	Total Number of Breakthrough Withdrawal Medication Doses Taken Week 1
NCT00980044 (4) [back to overview]	Subjective Opioid Withdrawal Total Adjective Score
NCT00980044 (4) [back to overview]	Subjective Opioid Withdrawal Adjective Total Score Week 2
NCT01112267 (7) [back to overview]	Change From Baseline in Short Form (SF)-36 Score at Day 29
NCT01112267 (7) [back to overview]	Percentage of Participants With Investigator's Global Assessment on Investigational Product
NCT01112267 (7) [back to overview]	Change From Baseline in Oswestry Disability Index (ODI) Korean Version Score at Day 29
NCT01112267 (7) [back to overview]	Percentage of Participants With Participants' Global Assessment on Investigational Product
NCT01112267 (7) [back to overview]	Change From Baseline in Pain Intensity at Day 29
NCT01112267 (7) [back to overview]	Percentage of Participants With Reduction in Pain Intensity
NCT01112267 (7) [back to overview]	Percentage of Participants With Pain Relief
NCT01188421 (1) [back to overview]	Mean Ratings on Clinical Opiate Withdrawal Scale (COWS) Measure of Withdrawal During Double-blind Taper (7-days) and Post-taper (7-days) Period.
NCT01267136 (2) [back to overview]	Efficacy of Two Different Liquid Pain Medications: Tramadol vs. Codeine/Acetaminophen During the Post-tonsillectomy Recovery Period.
NCT01267136 (2) [back to overview]	Number of Participants Reporting Side Effects During the Post-tonsillectomy Recovery Period.
NCT01307020 (3) [back to overview]	Percentage of Patients Achieving at Least 50 % of the Theoretical Maximum Total Pain Relief Score at 6 Hours Post-dosing.
NCT01307020 (3) [back to overview]	Percentage of Patients Using Rescue Medication at 6 Hours
NCT01307020 (3) [back to overview]	Percentage of Patients Achieving at Least 50 % of the Theoretical Maximum Total Pain Relief Score at 4, 8 and 12 Hours Post-dosing.
NCT01345162 (1) [back to overview]	Analgesic Efficacy
NCT01517711 (4) [back to overview]	Clinician-Administered PTSD Scale (CAPS)
NCT01517711 (4) [back to overview]	Clinical Global Impression -- Improvement (CGI-I) -- Subject
NCT01517711 (4) [back to overview]	Quick Inventory of Depressive Symptoms (QIDS)
NCT01517711 (4) [back to overview]	Visual Analog Scales (VAS)
NCT01598753 (1) [back to overview]	Number of Participants With a 30% Improvement in Pain or 20% Improvement in Function
NCT01728246 (4) [back to overview]	Change From Baseline in VAS-pain Score at Week 4
NCT01728246 (4) [back to overview]	Change From Baseline in Visual Analogue Scale for Pain (VAS-pain) Score at Week 2
NCT01728246 (4) [back to overview]	Change From Baseline in ODI Score at Week 4
NCT01728246 (4) [back to overview]	Percentage of Participants Who Discontinued Because of Rescue Medication
NCT01814878 (8) [back to overview]	Sum of Total Pain Relief and Sum of Pain Intensity Difference (SPRID)
NCT01814878 (8) [back to overview]	Sum of Pain Intensity Difference (SPID) at Hour 6, 12 and 24
NCT01814878 (8) [back to overview]	Time to the First Rescue Medication Administered Because of Insufficient Pain Relief
NCT01814878 (8) [back to overview]	Sum of Pain Intensity Difference (SPID) at Hour 48
NCT01814878 (8) [back to overview]	Patient Global Impression of Change (PGIC) Score
NCT01814878 (8) [back to overview]	Total Pain Relief (TOTPAR) Score
NCT01814878 (8) [back to overview]	Dosage of Rescue Medication Administered Because of Insufficient Pain Relief
NCT01814878 (8) [back to overview]	Number of Doses of Rescue Medication Administered Because of Insufficient Pain Relief
NCT01843660 (15) [back to overview]	Number of Participants With Pain Relief Score at Hour 1
NCT01843660 (15) [back to overview]	Pain Intensity Score Based on Numeric Rating Scale (NRS) at Hour 4
NCT01843660 (15) [back to overview]	Pain Intensity Score Based on Numeric Rating Scale (NRS) at Hour 3
NCT01843660 (15) [back to overview]	Pain Intensity Score Based on Numeric Rating Scale (NRS) at Hour 2
NCT01843660 (15) [back to overview]	Pain Intensity Score Based on Numeric Rating Scale (NRS) at Hour 1
NCT01843660 (15) [back to overview]	Number of Participants Who Required Additional Dosage Administration
NCT01843660 (15) [back to overview]	Pain Intensity Score Based on Numeric Rating Scale (NRS) at Hour 6
NCT01843660 (15) [back to overview]	Number of Participants With Analgesic Satisfaction Score
NCT01843660 (15) [back to overview]	Number of Participants With Overall Analgesic Satisfaction Score
NCT01843660 (15) [back to overview]	Number of Participants With Pain Relief Score at Hour 0.5
NCT01843660 (15) [back to overview]	Pain Intensity Score Based on Numeric Rating Scale (NRS) at Hour 0.5
NCT01843660 (15) [back to overview]	Number of Participants With Pain Relief Score at Hour 2
NCT01843660 (15) [back to overview]	Number of Participants With Pain Relief Score at Hour 3
NCT01843660 (15) [back to overview]	Number of Participants With Pain Relief Score at Hour 4
NCT01843660 (15) [back to overview]	Number of Participants With Pain Relief Score at Hour 6
NCT01902134 (4) [back to overview]	SPID8 (Sum of Pain Intensity Differences Over 8 Hours)
NCT01902134 (4) [back to overview]	Percentage of Responders According to PI-VAS (Pain Intensity - Visual Analogue Scale)
NCT01902134 (4) [back to overview]	SPID48 (Sum of Pain Intensity Differences Over First 48 Hours of the Multiple-dose Phase)
NCT01902134 (4) [back to overview]	Percentage of Responders According to 50% Max TOTPAR (Total Pain Relief)
NCT01904149 (4) [back to overview]	Percentage of Responders According to 50% Max TOTPAR (Total Pain Relief)
NCT01904149 (4) [back to overview]	Percentage of Responders According to PI-VAS (Pain Intensity - Visual Analogue Scale)
NCT01904149 (4) [back to overview]	SPID48 (Sum of Pain Intensity Differences Over 48 Hours of the Multiple-dose Phase)
NCT01904149 (4) [back to overview]	SPID8 (Sum of Pain Intensity Differences Over 8 Hours)
NCT01943435 (3) [back to overview]	Sense Wear Armband
NCT01943435 (3) [back to overview]	Self Paced Walking Test (SPWT)
NCT01943435 (3) [back to overview]	Swiss Spinal Stenosis (SSS) Questionnaire Score
NCT01983111 (6) [back to overview]	Clinical Global Impression of Change(CGIC)
NCT01983111 (6) [back to overview]	Change in the Quality of Life (EQ-5D) Score From Visit 1 (Baseline) to Week 6 Post-dose
NCT01983111 (6) [back to overview]	Change in the Pain Intensity Score (0-10 NRS) From Visit 1 (Baseline) to Week 2 of the Investigational Product Administration
NCT01983111 (6) [back to overview]	Change in the Pain Intensity Score (0-10 NRS) From Visit 1 (Baseline) to 6weeks After Treatment.
NCT01983111 (6) [back to overview]	Change From Baseline in Health-related Quality of Life Assessed by EuroQol Visual Analog Scale (EQ-5D VAS)
NCT01983111 (6) [back to overview]	Patient Global Impressions of Change(PGIC)
NCT02389361 (1) [back to overview]	Acute Pain
NCT02484859 (5) [back to overview]	Time to Achieve Intraoperative Bleeding Score < 3
NCT02484859 (5) [back to overview]	Postoperative Pain
NCT02484859 (5) [back to overview]	Intraoperative Bleeding Score
NCT02484859 (5) [back to overview]	Number of Participants With Postoperative Nausea and Vomiting
NCT02484859 (5) [back to overview]	Bleeding Rate
NCT02528253 (99) [back to overview]	Number of Participants Who Responded for Chronic Low Back Pain Responder Index at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56
NCT02528253 (99) [back to overview]	Number of Participants Who Responded for Chronic Low Back Pain Responder Index at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56
NCT02528253 (99) [back to overview]	Number of Participants Who Took Rescue Medication During Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, 56 and 64
NCT02528253 (99) [back to overview]	Number of Participants With Anti Tanezumab Antibodies
NCT02528253 (99) [back to overview]	Number of Participants With Anti Tanezumab Antibodies
NCT02528253 (99) [back to overview]	Number of Participants With Confirmed Orthostatic Hypotension
NCT02528253 (99) [back to overview]	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
NCT02528253 (99) [back to overview]	Number of Participants With Treatment-Emergent Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) up to Week 56
NCT02528253 (99) [back to overview]	Percentage of Participants Achieving Average LBPI Reduction of >=30 Percent(%), >=50%, >=70% and >=90% From Baseline at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56: Mixed Baseline Observation Carried Forward (BOCF)/Last Observation Carried Forward (LOCF)
NCT02528253 (99) [back to overview]	Percentage of Participants Achieving Average LBPI Reduction of >=30 Percent(%), >=50%, >=70% and >=90% From Baseline at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56: Mixed Baseline Observation Carried Forward (BOCF)/Last Observation Carried Forward (LOCF)
NCT02528253 (99) [back to overview]	Percentage of Participants Achieving Improvement of >=2 Points in Patient's Global Assessment (PGA) of Low Back Pain From Baseline at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Mixed Baseline Observation Carried Forward (BOCF)/ Last Observation CF (LOCF)
NCT02528253 (99) [back to overview]	Percentage of Participants Achieving Improvement of >=2 Points in Patient's Global Assessment (PGA) of Low Back Pain From Baseline at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Mixed Baseline Observation Carried Forward (BOCF)/ Last Observation CF (LOCF)
NCT02528253 (99) [back to overview]	Percentage of Participants Achieving RMDQ Reduction of >=30%, >=50%, >=70% and >=90% From Baseline at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Mixed Baseline Observation Carried Forward (BOCF)/Last Observation Carried Forward (LOCF)
NCT02528253 (99) [back to overview]	Percentage of Participants Achieving RMDQ Reduction of >=30%, >=50%, >=70% and >=90% From Baseline at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Mixed Baseline Observation Carried Forward (BOCF)/Last Observation Carried Forward (LOCF)
NCT02528253 (99) [back to overview]	Percentage of Participants With Adjudicated Joint Safety Outcomes
NCT02528253 (99) [back to overview]	Percentage of Participants With Cumulative Percent Change From Baseline in Daily Average Low Back Pain Intensity (LBPI) Score at Weeks 16, 24 and 56: Mixed Baseline Observation Carried Forward (BOCF)/Last Observation Carried Forward (LOCF)
NCT02528253 (99) [back to overview]	Percentage of Participants With Cumulative Percent Change From Baseline in Daily Average Low Back Pain Intensity (LBPI) Score at Weeks 16, 24 and 56: Mixed Baseline Observation Carried Forward (BOCF)/Last Observation Carried Forward (LOCF)
NCT02528253 (99) [back to overview]	Percentage of Participants With Cumulative Percent Change From Baseline in Roland Morris Disability Questionnaire (RMDQ) Score at Weeks 16, 24 and 56
NCT02528253 (99) [back to overview]	Percentage of Participants With Cumulative Percent Change From Baseline in Roland Morris Disability Questionnaire (RMDQ) Score at Weeks 16, 24 and 56
NCT02528253 (99) [back to overview]	Treatment Satisfaction Score Determined With Treatment Satisfaction Questionnaire for Medication Version II (TSQM v II) at Weeks 16 and 56
NCT02528253 (99) [back to overview]	Treatment Satisfaction Score Determined With Treatment Satisfaction Questionnaire for Medication Version II (TSQM v II) at Weeks 16 and 56
NCT02528253 (99) [back to overview]	Work Productivity and Activity Impairment Questionnaire for Low Back Pain (WPAI:LBP) Scores at Baseline: Observed Data
NCT02528253 (99) [back to overview]	Health Care Resource Utilization (HCRU): Number of Participants Who Used Any Aids/Devices for Doing Things
NCT02528253 (99) [back to overview]	Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 56: Participant Global Preference Assessment- Overall, do You Prefer The Drug That You Received in This Study to Previous Treatment?
NCT02528253 (99) [back to overview]	Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 56: Participant Global Preference Assessment- What is The Current or Most Recent Treatment You Were Receiving For Low Back Pain Before Enrolling?
NCT02528253 (99) [back to overview]	Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 56: Participant Willingness to Use Drug Again Assessment- Willing to Use The Same Drug That You Have Received in This Study For Your Low Back Pain Pain?
NCT02528253 (99) [back to overview]	Health Care Resource Utilization (HCRU): Number of Visits of Services Received Directly Related to Low Back Pain
NCT02528253 (99) [back to overview]	Number of Participants With Laboratory Test Abnormalities With Regard to Abnormal Baseline
NCT02528253 (99) [back to overview]	Change From Baseline in Average Low Back Pain Intensity (LBPI) Score for Tanezumab Versus (Vs) Placebo at Week 16
NCT02528253 (99) [back to overview]	Change From Baseline in Average Low Back Pain Intensity (LBPI) Score for Tanezumab Versus (Vs) Tramadol at Week 16
NCT02528253 (99) [back to overview]	Change From Baseline in Roland Morris Disability Questionnaire (RMDQ) at Week 16 for Tanezumab Versus (Vs) Placebo
NCT02528253 (99) [back to overview]	Number of Days of Rescue Medication Used at Week 64
NCT02528253 (99) [back to overview]	Number of Participants Who Took Rescue Medication During Week 64: Observed Data
NCT02528253 (99) [back to overview]	Number of Participants Who Withdrew Due to Lack of Efficacy
NCT02528253 (99) [back to overview]	Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Scores Average Pain at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data
NCT02528253 (99) [back to overview]	Number of Participants With Laboratory Test Abnormalities With Regard to Normal Baseline
NCT02528253 (99) [back to overview]	Percentage of Participants With Total Joint Replacements
NCT02528253 (99) [back to overview]	Time to Discontinuation Due to Lack of Efficacy
NCT02528253 (99) [back to overview]	Amount of Rescue Medication Used at Weeks 2, 4, 8, 12 and 16
NCT02528253 (99) [back to overview]	Change From Baseline in Average Low Back Pain Intensity (LBPI) Score at Weeks 2, 4, 8, 12, 24, 32, 40, 48 and 56
NCT02528253 (99) [back to overview]	Change From Baseline in Average Low Back Pain Intensity (LBPI) Score at Weeks 2, 4, 8, 12, 24, 32, 40, 48 and 56
NCT02528253 (99) [back to overview]	Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80
NCT02528253 (99) [back to overview]	Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80
NCT02528253 (99) [back to overview]	Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Average Pain at Week 64: Observed Data
NCT02528253 (99) [back to overview]	Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference Index at Week 64: Observed Data
NCT02528253 (99) [back to overview]	Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference Index at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data
NCT02528253 (99) [back to overview]	Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference With General Activity at Week 64: Observed Data
NCT02528253 (99) [back to overview]	Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference With General Activity at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data
NCT02528253 (99) [back to overview]	Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference With General Activity at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data
NCT02528253 (99) [back to overview]	Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference With Normal Work at Week 64: Observed Data
NCT02528253 (99) [back to overview]	Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference With Normal Work at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data
NCT02528253 (99) [back to overview]	Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference With Normal Work at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data
NCT02528253 (99) [back to overview]	Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference With Sleep at Week 64: Observed Data
NCT02528253 (99) [back to overview]	Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference With Sleep at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data
NCT02528253 (99) [back to overview]	Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference With Sleep at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data
NCT02528253 (99) [back to overview]	Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference With Walking Ability at Week 64: Observed Data
NCT02528253 (99) [back to overview]	Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference With Walking Ability at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data
NCT02528253 (99) [back to overview]	Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference With Walking Ability at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data
NCT02528253 (99) [back to overview]	Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Worst Pain at Week 64: Observed Data
NCT02528253 (99) [back to overview]	Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Score Worst Pain at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56
NCT02528253 (99) [back to overview]	Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Score Worst Pain at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56
NCT02528253 (99) [back to overview]	Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Scores Average Pain at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data
NCT02528253 (99) [back to overview]	Change From Baseline in Daily Average Low Back Pain Intensity (LBPI) Score at Week 64
NCT02528253 (99) [back to overview]	Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 16, 56 and 80
NCT02528253 (99) [back to overview]	Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 16, 56 and 80
NCT02528253 (99) [back to overview]	Change From Baseline in Heart Rate (as Assessed by ECG) at Weeks 16, 56 and 80
NCT02528253 (99) [back to overview]	Change From Baseline in Heart Rate (as Assessed by ECG) at Weeks 16, 56 and 80
NCT02528253 (99) [back to overview]	Change From Baseline in Heart Rate at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80
NCT02528253 (99) [back to overview]	Change From Baseline in Heart Rate at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80
NCT02528253 (99) [back to overview]	Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80
NCT02528253 (99) [back to overview]	Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80
NCT02528253 (99) [back to overview]	Change From Baseline in Patient's Global Assessment (PGA) of Low Back Pain at Week 64: Observed Data
NCT02528253 (99) [back to overview]	Change From Baseline in Patient's Global Assessment (PGA) of Low Back Pain at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56
NCT02528253 (99) [back to overview]	Change From Baseline in Patient's Global Assessment (PGA) of Low Back Pain at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56
NCT02528253 (99) [back to overview]	Change From Baseline in Roland Morris Disability Questionnaire (RMDQ) Score at Weeks 64 and 80: Observed Data
NCT02528253 (99) [back to overview]	Change From Baseline in Roland Morris Disability Questionnaire (RMDQ) Total Score at Weeks 2, 4, 8, 16 (for Tanezumab vs Tramadol) 24, 32, 40, 48 and 56
NCT02528253 (99) [back to overview]	Change From Baseline in Roland Morris Disability Questionnaire (RMDQ) Total Score at Weeks 2, 4, 8, 16 (for Tanezumab vs Tramadol) 24, 32, 40, 48 and 56
NCT02528253 (99) [back to overview]	Change From Baseline in Work Productivity and Activity Impairment Questionnaire for Low Back Pain (WPAI:LBP) Scores at Weeks 16, 56 and 64
NCT02528253 (99) [back to overview]	Change From Baseline in Work Productivity and Activity Impairment Questionnaire for Low Back Pain (WPAI:LBP) Scores at Weeks 16, 56 and 64
NCT02528253 (99) [back to overview]	Change From Screening in Survey of Autonomic Symptom (SAS) Scores at Weeks 24, 56 and 80
NCT02528253 (99) [back to overview]	Change From Screening in Survey of Autonomic Symptom (SAS) Scores at Weeks 24, 56 and 80
NCT02528253 (99) [back to overview]	European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Dimensions Score
NCT02528253 (99) [back to overview]	European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Overall Health Utility Score/ Index Value
NCT02528253 (99) [back to overview]	Health Care Resource Utilization (HCRU): Duration Since Quitting Job Due to Low Back Pain
NCT02528253 (99) [back to overview]	Health Care Resource Utilization (HCRU): Number of Nights Stayed in the Hospital Due to Low Back Pain
NCT02528253 (99) [back to overview]	Health Care Resource Utilization (HCRU): Number of Nights Stayed in the Hospital Due to Low Back Pain
NCT02528253 (99) [back to overview]	Health Care Resource Utilization (HCRU): Number of Nights Stayed in the Hospital Due to Low Back Pain
NCT02528253 (99) [back to overview]	Health Care Resource Utilization (HCRU): Number of Nights Stayed in the Hospital Due to Low Back Pain
NCT02528253 (99) [back to overview]	Health Care Resource Utilization (HCRU): Number of Participants Hospitalized Due to Low Back Pain
NCT02528253 (99) [back to overview]	Health Care Resource Utilization (HCRU): Number of Participants Who Quit Job Due to Low Back Pain
NCT02528253 (99) [back to overview]	Health Care Resource Utilization (HCRU): Number of Participants Who Visited the Emergency Room Due to Low Back Pain
NCT02528253 (99) [back to overview]	Health Care Resource Utilization (HCRU): Number of Visits of Services Received Directly Related to Low Back Pain
NCT02528253 (99) [back to overview]	Health Care Resource Utilization (HCRU): Number of Visits of Services Received Directly Related to Low Back Pain
NCT02528253 (99) [back to overview]	Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference Index at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data
NCT02528253 (99) [back to overview]	Health Care Resource Utilization (HCRU): Number of Visits of Services Received Directly Related to Low Back Pain
NCT02528253 (99) [back to overview]	Health Care Resource Utilization (HCRU): Number of Visits of Services Received Directly Related to Low Back Pain
NCT02528253 (99) [back to overview]	Health Care Resource Utilization (HCRU): Number of Visits to the Emergency Room Due to Low Back Pain
NCT02528253 (99) [back to overview]	Health Care Resource Utilization (HCRU): Number of Visits to the Emergency Room Due to Low Back Pain
NCT02528253 (99) [back to overview]	Number of Days of Rescue Medication Used at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56
NCT02777970 (6) [back to overview]	% of Patients Requiring RM (Rescue Medication)
NCT02777970 (6) [back to overview]	% of Patients Achieving 50% of Max TOTPAR
NCT02777970 (6) [back to overview]	% of Patients Achieving at Least 30% of PI (Pain Intensity) Reduction Over 8 Hours Post-dose
NCT02777970 (6) [back to overview]	PGE (Patient Global Evaluation)
NCT02777970 (6) [back to overview]	Time to Confirmed FPPAR (First Perceptible Pain Relief)
NCT02777970 (6) [back to overview]	TOTPAR6 (Total Pain Relief Over 6 Hours Post-dose)
NCT02964416 (10) [back to overview]	Haemodynamic Parameters at the Time of Emergence and Postextubation
NCT02964416 (10) [back to overview]	Haemodynamic Parameters at the Time of Emergence and Postextubation
NCT02964416 (10) [back to overview]	Measure the Quality of Emergence From General Anaesthesia by Measuring the Frequency of Episodes of Denaturation
NCT02964416 (10) [back to overview]	Measure the Quality of Emergence From General Anaesthesia by Measuring the Frequency of Cough on Cough Scale.
NCT02964416 (10) [back to overview]	Measure the Quality of Emergence From General Anaesthesia by Measuring the Frequency of Laryngospasm and Bronchospasm.
NCT02964416 (10) [back to overview]	Effect of Tramadol on Quality of Emergence Measured by Extubation Response Through Mointoring Requirement of Analgesia
NCT02964416 (10) [back to overview]	Effect of Tramadol on Quality of Emergence Measured by Extubation Response Through Monitoring Convulsions
NCT02964416 (10) [back to overview]	Effect of Tramadol on Quality of Emergence Measured by Extubation Response Through Monitoring GCS
NCT02964416 (10) [back to overview]	Effect of Tramadol on Quality of Emergence Measured by Extubation Response Through Monitoring PONV
NCT02964416 (10) [back to overview]	Haemodynamic Parameters at the Time of Emergence and Postextubation
NCT03108482 (1) [back to overview]	Sum of Pain Intensity Differences (SPID)
NCT03290378 (1) [back to overview]	The Sum of Pain Intensity Differences (SPID) Through 48 Hours Post First Dose
NCT03395808 (1) [back to overview]	Adverse Events
NCT03472469 (10) [back to overview]	Number of Hospital Days
NCT03472469 (10) [back to overview]	Number of Intensive Care Unti (ICU) Days
NCT03472469 (10) [back to overview]	Pain as Assessed by Score on the Numeric Rating Scale (NRS)
NCT03472469 (10) [back to overview]	Number of Participants With Any Opioid-related Complications
NCT03472469 (10) [back to overview]	Pharmacy Costs
NCT03472469 (10) [back to overview]	Overall Costs
NCT03472469 (10) [back to overview]	Opioid Use Per Day
NCT03472469 (10) [back to overview]	Number of Ventilator Days
NCT03472469 (10) [back to overview]	Number of Participants Discharged From the Hospital With an Opioid Prescription
NCT03472469 (10) [back to overview]	Pain as Assessed by Score on the Behavioral Pain Scale (BPS)
NCT03714672 (10) [back to overview]	Time to Onset of First Perceptible Pain Relief
NCT03714672 (10) [back to overview]	Time to Onset of Meaningful Pain Relief
NCT03714672 (10) [back to overview]	Total Pain Relief at 6 Hours Post-dose (TOTPAR6)
NCT03714672 (10) [back to overview]	Total Pain Relief at 8 Hours Post-dose (TOTPAR8)
NCT03714672 (10) [back to overview]	Summed Pain Intensity Difference (SPID) at 4, 6, 8, and 24 Hours Post-dose
NCT03714672 (10) [back to overview]	Time to Achieve a 50 Percent Reduction in Baseline Pain (Pain at Least Half Gone)
NCT03714672 (10) [back to overview]	Pain Relief Expressed as Total Pain Relief (TOTPAR) Over the 4 Hours Post-dose Period (TOTPAR4)
NCT03714672 (10) [back to overview]	Incidence and Type of Adverse Events
NCT03714672 (10) [back to overview]	Subject's Global Evaluation of the Treatment
NCT03714672 (10) [back to overview]	Time to Intake of First Rescue Medication Dose
NCT04004481 (6) [back to overview]	Number of Participants With Nausea and Vomiting After Tramadol
NCT04004481 (6) [back to overview]	Serum Concentration of Tramadol and Tramadol Metabolites With Respect to Metabolic Phenotype
NCT04004481 (6) [back to overview]	Analgesic Effect of Tramadol Measured by Numeric Rating Scale (NRS)
NCT04004481 (6) [back to overview]	Analgesic Effect of Tramadol Measured by Critical Care Pain Observation Tool (CPOT)
NCT04004481 (6) [back to overview]	Number of Patients With Respiratory Depression After Tramadol
NCT04004481 (6) [back to overview]	Length of ICU Stay
NCT04766996 (2) [back to overview]	Nebraska Interprofessional Education Attitude Scale (NIPEAS) Score for Professional Staff Arm
NCT04766996 (2) [back to overview]	Total Post-operative Opioid Requirements With Non-opioid Drug Regimen

Discrimination Effects Assessed by Discrete Choice

"During discrete choice, volunteers were given three choices (placebo, hydromorphone, methylphenidate) and were asked to choose which of the training drugs they thought they received. The outcome measure illustrates the percentage of participants who chose either placebo, hydromorphone, or methylphenidate during each drug condition (i.e., Placebo, Hydromorphone 8 mg, Tramadol 50 mg, etc.), ranging from 0-100.~The outcome measure represents the percentage of participants who chose either placebo, opioid agonist, or stimulant across each drug condition." (NCT00499746)
Timeframe: 1 day

,,,,,,,,

Intervention	percentage of drug identification (Number)
	Placebo	Hydromorphone	Methylphenidate
Hydromorphone 4 mg	25	75	0
Hydromorphone 8 mg	0	100	0
Methylphenidate 30 mg	0	0	100
Methylphenidate 60 mg	0	0	100
Placebo 0 mg	100	0	0
Tramadol 100 mg	75	25	0
Tramadol 200 mg	25	75	0
Tramadol 400 mg	25	63	12
Tramadol 50 mg	100	0	0

Intervention	mm (Mean)
Placebo 0 mg	-0.5
Hydromorphone 4 mg	-1.2
Hydromorphone 8 mg	-1.9
Methylphenidate 30 mg	-0.6
Methylphenidate 60 mg	-0.3
Tramadol 50 mg	-0.5
Tramadol 100 mg	-0.2
Tramadol 200 mg	-0.8
Tramadol 400 mg	-0.8

Intervention	percentage of drug identification (Number)
	Placebo	Opioid Agonist	Stimulant
Hydromorphone 4 mg	25	75	0
Hydromorphone 8 mg	0	100	0
Methylphenidate 30 mg	0	0	100
Methylphenidate 60 mg	0	0	100
Placebo 0 mg	100	0	0
Tramadol 100 mg	75	25	0
Tramadol 200 mg	37	63	0
Tramadol 400 mg	25	63	12
Tramadol 50 mg	100	0	0

Intervention	percent signal change (Least Squares Mean)
	ACC	AIC_L	AIC_R	MIC_L	MIC_R	PIC_L	PIC_R	Amyg_L	Amyg_R	S1	S2	SensTHAL	MRF	NucCun	PAG
Placebo	7.4	30.8	17.1	30.0	18.3	-0.3	6.5	8.5	21.7	-2.9	10.8	9.6	11.7	12.9	2.5
Pregabalin	-17.3	8.1	11.1	3.8	8.6	-6.8	-13.6	-5.7	-1.4	-28.5	2.5	8.0	7.0	1.1	-3.8
Tramadol	18.6	23.3	21.9	23.4	13.4	-5.8	2.9	5.5	20.3	-4.1	-3.2	16.5	6.4	-0.9	-15.3

Intervention	units on a scale (Least Squares Mean)
	Last 7 days	Last 3 days
Placebo	6.40	6.33
Pregabalin	5.57	5.46
Tramadol	5.28	5.10

Intervention	Units on a scale (Mean)
	Baseline: Phiysical functioning (n=71,76)	Change at Day 43: Physical functioning (n=63, 68))	Baseline: Physical role limitation (n=71,76)	Change at Day 43:Physical role limitation(n=62,68)	Baseline: Pain (n=71,76)	Change at Day 43: Pain (n=63, 68)	Baseline: General health (n=71,76)	Change at Day 43: General health (n=63, 68)	Baseline: Emotional role limitation (n=71,76)	Change at Day43:Emotional role limitation(n=63,68)	Baseline: Energy/Fatigue (n=71,76)	Change at Day 43: Energy/Fatigue (n=63, 68)	Baseline: Emotional well-being (n=71,76)	Change at Day 43: Emotional well being (n=63, 68)	Baseline: Social functioning (n=71,76)	Change at Dya 43: Social functioning (n=63, 68)
Gabapentin	60.6	3.2	49.3	10.7	50.8	10.4	40.3	4.4	50.4	18.1	42.6	10.0	61.4	7.0	72.2	5.5
Tramadol Hydrochloride/ Acetaminophen	56.3	3.2	42.3	13.7	49.3	15.6	38.0	4.6	46.9	12.7	39.4	5.7	57.2	5.3	68.3	9.9

Intervention	Percentage of Participants (Number)
	Day 15: Became worse	Day 15: No change	Day 15: Relieved a little	Day 15: Relieved moderately	Day 15: Relieved a lot	Day 15: Completely resolved	Day 29: Became worse	Day 29: No change	Day 29: Relieved a little	Day 29: Relieved moderately	Day 29: Relieved a lot	Day 29: Completely resolved	Day 43: Became worse	Day 43: No change	Day 43: Relieved a little	Day 43: Relieved moderately	Day 43: Relieved a lot	Day 43: Completely resolved
Gabapentin	4.0	14.5	34.2	21.1	26.3	0.0	1.3	10.5	29.0	14.5	44.7	0.0	1.3	11.8	25.0	15.8	42.1	4.0
Tramadol Hydrochloride/ Acetaminophen	1.4	12.7	31.0	26.8	26.8	1.4	4.2	9.9	25.4	21.1	38.0	1.4	2.8	7.0	22.5	19.7	46.5	1.4

Intervention	Percentage of participants (Number)
	Bad	No change	Good	Very good
Gabapentin	12.5	29.2	41.7	16.7
Tramadol Hydrochloride/ Acetaminophen	4.5	29.9	50.8	14.9

Intervention	Units on a scale (Mean)
	Baseline	Change at Day 43
Gabapentin	6.30	2.76
Tramadol Hydrochloride/ Acetaminophen	6.65	3.15

Intervention	Units on a scale (Mean)
	Baseline: Pain severity score (n=68, 73)	Change at Day 43: Pain severity score (n=60, 60)	Baseline: Pain interference score (n=71, 76)	Change at Day 43:Pain interference score(n=63, 68)
Gabapentin	4.9	0.1	29.8	-8.8
Tramadol Hydrochloride/ Acetaminophen	4.5	0.1	30.2	-11.0

Intervention	units on a scale (Mean)
	Day 29	Change at Day 85
Non-steroidal Anti-inflammatory Drugs (NSAIDs)	3.82	0.14
Tramadol Hydrochloride Plus Acetaminophen	3.81	0.83

Intervention	percent signal change (Least Squares Mean)
	ACC	AIC_L	AIC_R	MIC_L	MIC_R	PIC_L	PIC_R	Amyg_L	Amyg_R	S1	S2	SensTHAL	MRF	NucCun	PAG
Placebo	0.2	20.2	20.2	9.0	0.7	0.8	6.3	-3.4	-3.8	14.6	13.5	6.7	-1.7	-1.8	-5.0
Pregabalin	-22.3	-13.5	-10.6	-7.6	-9.2	-14.9	-17.2	-14.3	-10.3	-31.6	-0.4	3.9	1.5	1.0	1.6
Tramadol	-3.7	18.2	10.3	9.7	2.8	-8.1	2.4	1.5	2.0	-4.5	9.6	-2.8	-6.6	-8.2	-12.0

Intervention	percent signal change (Least Squares Mean)
	ACC	AIC_L	AIC_R	MIC_L	MIC_R	PIC_L	PIC_R	Amyg_L	Amyg_R	S1	S2	SensTHAL	MRF	NucCun	PAG
Placebo	83.3	118.7	104.0	100.4	92.0	34.2	91.8	36.4	67.0	27.7	74.5	10.4	37.7	40.5	44.6
Pregabalin	102.2	92.1	121.7	93.4	106.6	31.2	75.3	29.7	77.5	-49.0	73.6	19.4	34.3	38.7	63.3
Tramadol	92.5	103.4	104.6	105.2	71.1	44.6	95.5	24.9	57.2	37.7	94.6	0.8	25.5	27.7	53.6

Intervention	participants (Number)
	Day 29; Pain relieved (n=56, 52)	Day 57; Pain relieved (n=47, 41)	Day 85; Pain relieved (n=55, 56)
Non-steroidal Anti-inflammatory Drugs (NSAIDs)	49	32	42
Tramadol Hydrochloride Plus Acetaminophen	42	28	35

Intervention	participants (Number)
	Very bad	Bad	Moderate	Good	Very good
Non-steroidal Anti-inflammatory Drugs (NSAIDs)	1	2	21	29	4
Tramadol Hydrochloride Plus Acetaminophen	1	11	22	21	2

Intervention	participants (Number)
	Day 29; No tenderness(n=56, 52)	Day 29; Complaint of tenderness (n=56, 52)	Day 29; CTW (n=56, 52)	Day 29; Wincing and attempt to withdraw (n=56, 52)	Day 57; No tenderness(n=47, 41)	Day 57; Complaint of tenderness (n=47, 41)	Day 57; CTW (n=47, 41)	Day 57; wincing and attempt to withdraw(n=47, 41)	Day 85; No tenderness(n=55, 56)	Day 85; Complaint of tenderness (n=55, 56)	Day 85; CTW (n=55, 56)	Day 85; Wincing and attempt to withdraw(n=55, 56)
Non-steroidal Anti-inflammatory Drugs (NSAIDs)	33	22	0	1	33	14	0	0	39	15	0	1
Tramadol Hydrochloride Plus Acetaminophen	37	14	1	0	30	10	1	0	44	10	2	0

Intervention	participants (Number)
	Day 29; No swelling (n=56, 52)	Day 29; PCFF (n=56, 52)	Day 57; No swelling (n=47, 41)	Day 57; PCFF (n=47, 41)	Day 85; No swelling (n=55, 56)	Day 85; PCFF (n=55, 56)	Day 85; Patellar ballotment (n=55, 56)
Non-steroidal Anti-inflammatory Drugs (NSAIDs)	52	4	43	4	53	1	1
Tramadol Hydrochloride Plus Acetaminophen	45	7	38	3	46	9	1

Intervention	participants (Number)
	1	2	3	4	5	6	7	8	9	10
Celecoxib	24	16	19	31	35	32	35	55	56	70
Tramadol HCL	15	22	20	33	40	30	37	46	77	44

Intervention	participants (Number)
	Week 1, Excellent	Week 1, Very Good	Week 1, Good	Week 1, Fair	Week 1, Poor	Week 3, Excellent	Week 3, Very Good	Week 3, Good	Week 3, Fair	Week 3, Poor	Week 6/ET, Excellent	Week 6/ET, Very Good	Week 6/ET, Good	Week 6/ET, Fair	Week 6/ET, Poor
Celecoxib	46	97	126	78	23	52	104	122	53	23	91	123	76	51	32
Tramadol HCL	38	83	137	57	18	41	97	105	51	14	68	112	90	51	44

Intervention	participants (Number)
	Improved	No Change	Worsened
Celecoxib	108	264	3
Tramadol HCL	107	259	1

Intervention	participants (Number)
	0 to 1 (Improvement)	1 to 1 (No change)	0 to 0 (No change)	1 to 0 (worsening)
Celecoxib	82	94	171	26
Tramadol HCL	74	70	192	29

Intervention	scores on a scale (Mean)
	Time Scale (n=241, 239)	Physical Scale (n=270, 254)	Output Scale (n=256, 246)	Mental-Interpersonal Scale (n=266, 252)	Index Scale (n=223, 220)
Celecoxib	-11.55	-13.68	-11.44	-9.06	-3.10
Tramadol HCL	-13.58	-12.65	-11.69	-9.54	-3.14

Intervention	scores on a scale (Mean)
	How Much Pain Now	Worst Pain in Past 24 Hours	Average Pain in Past 24 Hours	Pain Interfered With General Activity	Pain Interfered With Mood	Pain Interfered With Walking Activity	Pain Interfered With Relations With Others	Pain Interfered With Sleep	Pain Interfered With Normal Work	Pain Interfered With Enjoyment of Life	Pain Interference Subscale
Celecoxib	-2.87	-2.84	-2.64	-2.62	-2.38	-2.26	-1.79	-2.52	-2.57	-2.43	-2.37
Tramadol HCL	-2.88	-2.87	-2.59	-2.57	-2.25	-2.36	-1.74	-2.51	-2.46	-2.43	-2.33

tramadol

Description

Cross-References

Synonyms (106)

Research Excerpts

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Actions

Treatment

Toxicity

Pharmacokinetics

Compound-Compound Interactions

Bioavailability

Dosage Studied

Roles (13)

Drug Classes (1)

Pathways (2)

Protein Targets (6)

Potency Measurements

Inhibition Measurements

Activation Measurements

Biological Processes (81)

Molecular Functions (30)

Ceullar Components (28)

Bioassays (27)

Research

Studies (3,410)

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Research Demand Index: 157.78

Study Types

Clinical Trials (302)

Trial Overview

Trial Outcomes

Discrimination Effects Assessed by Discrete Choice

Physiological Effects Assessed by Peak Change From Baseline Pupil Diameter

Peak Change From Baseline Stimulant Effects Assessed by the Visual Analog Scale (VAS)

Acquisition of Discrimination Assessed by Accuracy of the Discrimination Test

Peak Change From Baseline Opioid Agonist Effects Assessed by the Visual Analog Scale (VAS)

Physiologic Effects Assessed by the Pharmacological Class Questionnaire

Discrimination Effects Assessed by Point Distribution

Discrimination Effects Assessed by Operant Responses

Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa)

Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc)

Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH)

Present Pain Intensity Score (PPIS)

Daily Pain Score

Change From Baseline in Short Form-36 (SF-36) Score at Day 43

Percentage of Participants With Pain Relief

Overall Assessment of Study Medication by Participants

Overall Assessment of Study Medication by Investigator

Change From Baseline in Pain Intensity Score at Day 43

Change From Baseline in Brief Pain Inventory (BPI) Score at Day 43

Change From Day 29 in Pain Intensity Score at Day 85

Number of Participants With Pain Relief

Number of Participants With Overall Assessment on Study Drug by Participants

Number of Participants With Overall Assessment on Study Drug by Investigator

Number of Participants With Categorical Tenderness

Number of Participants With Categorical Swelling

Change From Day 29 in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Total Score at Day 85

Patient's Satisfaction Questionnaire (With Walking and Bending Ability Scale)

Patient's Satisfaction Questionnaire (With Pain Relief Scale)

Patient's Global Evaluation of Study Medication

Patient's Global Assessment of Disease Activity

Number of Subjects With Change From Baseline in MOS Optimal Sleep Scale Scores

Chronic Low Back Pain Responders Based on VAS, Patient's Global, and RMDQ

Change From Baseline in Work Limitations Questionnaire (WLQ)

Change From Baseline in Modified Brief Pain Inventory (m-BPI-sf)

Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale

Change From Baseline in Severity of Low Back Pain as Measured by Visual Analogue Scale (VAS)

Physician's Global Assessment of Disease Activity

Change From Baseline in Roland-Morris Disability Questionnaire (RMDQ) Total Score

Treatment Responders Based on the Numerical Rating Scale-Pain (NRS-Pain)

Change From Baseline in Severity of Chronic Low Back Pain as Measured by NRS-Pain

Gastro-intestinal Symptoms

Wound Healing

Dizziness/Sleepiness

Compliance to Base Medication

Satisfaction With Pain Medication

Patient Assessed Overall Satisfaction With Surgery/Outcome

Summary of Pain Scores, Day 1-7 of Visual Analogue Scale Grading of Pain

Intervention	scores on a scale (Mean)
	Sleep Disturbance (n=374, 367)	Snoring (n=372, 365)	Awaken Shortness of Breath, Headache (n=374, 367)	Quantity of Sleep (n=373, 365)	Sleep Adequacy (n=373, 367)	Somnolence (n=374, 366)	Sleep Problem Index I (n=373, 367)	Sleep Problem Index II (n=373, 367)
Celecoxib	-17.91	-7.53	-8.61	0.00	7.32	-9.63	-11.59	-12.97
Tramadol HCL	-16.34	-5.10	-6.21	0.58	9.67	-7.01	-10.54	-11.82

Intervention	Patients. (Number)
	satisfied	neutral	unsatisfied
Control Tramadol	44	4	1
Etoricoxib	45	4	0

Intervention	units on a scale (Mean)
	Day 1; 2 hours after dosing (n=274)	Day 1; 4 hours after dosing (n=274)	Day 8; 2 hours after dosing (n=219)	Day 8; 4 hours after dosing (n=219)
Tramadol Hydrochloride and Acetaminophen (Open-Label)	1.6	1.9	1.9	2.2

Intervention	units on a scale (Mean)
	Day 1 (n=274)	Day 8 (n=219)
Tramadol Hydrochloride and Acetaminophen (Open-Label)	3.5	4.1

Intervention	units on a scale (Mean)
	Day 1 (n=84, 89)	Day 8 (n=74, 48)	Day 15 (n=67, 41)	Day 22 (n=63, 40)	Day 28 (n=72, 47)
Placebo (Double-Blind)	2.3	2.6	3.3	3.6	3.3
Tramadol Hydrochloride and Acetaminophen (Double-Blind)	3.5	3.8	4.1	4.3	4.2

Intervention	units on a scale (Mean)
	Day 1 (n=160)	Change at Day 14 (n=126)
Tramadol Hydrochloride and Acetaminophen (Open-Label)	9.1	-2.6

Intervention	units on a scale (Mean)
	Day 1 (n=55, 57)	Change at Day 28 (n=55, 57)
Placebo (Double-Blind)	6.0	0.8
Tramadol Hydrochloride and Acetaminophen (Double-Blind)	6.5	-0.5

Intervention	units on a scale (Mean)
	Day 1; 2 hours after dosing (n=84, 89)	Day 1; 4 hours after dosing (n=84, 89)	Day 8; 2 hours after dosing (n=74, 48)	Day 8; 4 hours after dosing (n=74, 48)	Day 15; 2 hours after dosing (n=67, 41)	Day 15; 4 hours after dosing (n=67, 41)	Day 22; 2 hours after dosing (n=63, 40)	Day 22; 4 hours after dosing (n=63, 40)	Day 28; 2 hours after dosing (n=72, 47)	Day 28; 4 hours after dosing (n=72, 47)
Placebo (Double-Blind)	1.2	1.2	1.4	1.6	1.8	1.9	2.0	2.1	1.8	1.9
Tramadol Hydrochloride and Acetaminophen (Double-Blind)	1.9	2.0	2.1	2.3	2.2	2.4	2.3	2.4	2.2	2.4

Intervention	units on a scale (Mean)
	Day 1; Pre-dose (n=84, 89)	Day 1; 2 hours after dosing (n=84, 89)	Day 1; 4 hours after dosing (n=84, 89)	Day 8; Pre-dose (n=74, 48)	Day 8; 2 hours after dosing (n=74, 48)	Day 8; 4 hours after dosing (n=74, 48)	Day 15; Pre-dose (n=67, 41)	Day 15; 2 hours after dosing (n=67, 41)	Day 15; 4 hours after dosing (n=67, 41)	Day 22; Pre-dose (n=63, 40)	Day 22, 2 hours after dosing (n=63, 40)	Day 22; 4 hours after dosing (n=63, 40)	Day 28; Pre-dose (n=72, 47)	Day 28; 2 hours after dosing (n=72, 47)	Day 28; 4 hours after dosing (n=72, 47)
Placebo (Double-Blind)	1.2	1.1	1.1	1.2	1.1	1.1	1.1	1.0	0.9	1.2	1.0	1.0	1.2	1.0	1.0
Tramadol Hydrochloride and Acetaminophen (Double-Blind)	1.2	1.0	1.0	1.2	1.0	0.9	1.1	1.0	0.8	1.1	1.0	0.9	1.1	1.0	0.9

Intervention	units on a scale (Mean)
	Day 1; Pre-dose (n=275)	Day 1; 2 hours after dosing (n=274)	Day 1; 4 hours after dosing (n=274)	Day 8; Pre-dose (n=219)	Day 8; 2 hours after dosing (n=219)	Day 8; 4 hours after dosing (n=219)
Tramadol Hydrochloride and Acetaminophen (Open-Label)	1.7	1.2	1.1	1.2	1.0	0.9