digoxin

Research Excerpts

Overview

Digoxin is a cardiac glycoside, derived from the plant Digitalis purpurea. Digoxin is used to control rapid ventricular rates in atrial fibrillation and to reduce the hospitalizations due to heart failure.

Excerpt	Reference	Relevance
"Digoxin is a drug that is commonly used to treat congestive heart failure. "	( Characterization of digoxin uptake in sandwich-cultured human hepatocytes. Bi, YA; Chupka, J; Duignan, DB; Kimoto, E; Xiao, Y, 2011)	2.14
"Digoxin is a cardiac glycoside, derived from the plant Digitalis purpurea. "	( Digoxin Impact on Heart Failure Patients with Atrial Fibrillation. Abo-Elseoud, M; Artopoulou, E; Gerakaris, A; Koniari, I; Kounis, N; Mplani, V; Mulita, F; Tsigkas, G; Velissaris, D, 2022)	3.61
"Digoxin is a cardiac glycoside obtained from the leaves of the foxglove plant, Digitalis lanata. "	( Development and validation of a risk prediction nomogram for serious arrhythmias in acute digoxin toxicity among pediatrics: A multicenter study. El Gameel, D; Elgebally, EI; Fayed, MM; Sharif, AF; Shoeib, O, 2023)	2.57
"Digoxin is a commonly prescribed drug in the management of heart failure and atrial fibrillation. "	( A myriad of electrocardiographic findings associated with digoxin use. Djohan, AH; Kong, WK; Lin, W; Poh, KK; Sia, CH; Singh, D, 2020)	2.25
"Digoxin is a cardiac glycoside, used to control rapid ventricular rates in atrial fibrillation and to reduce the hospitalizations due to heart failure. "	( Digoxin therapeutic drug monitoring: age influence and adverse events. Ben Sassi, M; Charfi, R; Daghfous, R; Gaies, E; Jebabli, N; Trabelsi, S, 2020)	3.44
"Digoxin is a cardiac glycoside used as drug in case of heart problems, including congestive heart failure, atrial fibrillation or flutter, and certain cardiac arrhythmias. "	( Digoxin: Pharmacology and toxicology-A review. Kuca, K; Nepovimova, E; Patocka, J; Wu, W, 2020)	3.44
"Digoxin is a cardiac glycoside that is used for the treatment of heart failure and atrial fibrillation. "	( Continuous venovenous hemodialysis may be effective in digoxin removal in digoxin toxicity: A case report. Aygun, G; Dogan, AF; Gokalp, C; Kurultak, I; Ustundag, S, 2020)	2.25
"Digoxin is a safe treatment for management of fetal tachyarrhythmias. "	( Maternal effects induced by oral digoxin during treatment of fetal tachyarrhythmia: Case series and literature review. Antiñolo, G; Chimenea, Á; García-Díaz, L; Méndez, A, 2021)	2.35
"Digoxin is a cardiac glycoside that was introduced to cardiovascular medicine more than 200 years ago. "	( Population Pharmacokinetic Studies of Digoxin in Adult Patients: A Systematic Review. Abdel Jalil, M; Abdullah, N; Abu-Hammour, K; Alsous, M, 2021)	2.34
"Digoxin is a member of cardiac glycosides and recent studies show that digoxin plays anticancer role in several types of cancer. "	( The combination of digoxin and GSK2606414 exerts synergistic anticancer activity against leukemia in vitro and in vivo. Bai, H; Shi, L; Wang, XY; Yang, YX; Zhang, XC; Zhang, XH; Zhou, SF; Zhou, ZW, 2017)	2.23
"Digoxin is a kind of plant-derived cardiac glycoside that is mainly used to treat heart diseases, especially in congestive heart failure or arrhythmia. "	( Anti-proliferative effect of digoxin on breast cancer cells via inducing apoptosis. Han, XC; Hu, WN; Niu, FL; Yan, JY; Zhang, JH; Zhao, YT, 2017)	2.19
"Digoxin is a high-alert medication because of its narrow therapeutic range and high drug-to-drug interactions (DDIs). "	( Improvement of Adequate Digoxin Dosage: An Application of Machine Learning Approach. Hu, YH; Huang, MW; Tai, CT; Tsai, CF, 2018)	2.23
"Digoxin is a glycosidic, cardiotonic plant extract with a narrow therapeutic window. "	( Effect of purple grape juice on the pharmacokinetics of digoxin: Results of a food-drug interaction study . Ju, Y; Qiu, W; Song, X; Zhao, H, 2019)	2.2
"Digoxin is a potent inhibitor of HIF-1α synthesis, and we hypothesized that its use reduces the incidence of GIAD and GIB in patients with CF-LVAD."	( Digoxin Is Associated With a Decreased Incidence of Angiodysplasia-Related Gastrointestinal Bleeding in Patients With Continuous-Flow Left Ventricular Assist Devices. Chinnadurai, T; Forest, SJ; Goldstein, DJ; Jorde, UP; Patel, SR; Saeed, O; Shin, JJ; Shitole, SG; Sims, DB; Vlismas, PP; Vukelic, S; Xue, X, 2018)	2.64
"Digoxin poisoning is a frequent reason for seeking emergency care. "	( Immediate and 30 days mortality in digoxin poisoning cases attended in the Hospital Emergency Services of Catalonia, Spain. Calpe Perarnau, X; Clemente Rodríguez, C; Córdoba Ruiz, F; Galicia Paredes, M; García Gibert, L; Nogué Xarau, S; Salgado García, E; Supervía Caparrós, A, 2019)	2.23
"Digoxin is a cardiac glycoside which is widely used in cardiovascular medicine. "	( The effect of melatonin on digoxin‑induced cardiac damage in cardiomyocytes. Oncel, CR; Ovey, IS, )	1.87
"Digoxin is a highly toxic drug and consequently is routinely measured in sera of treated patients."	( Production and characterization of recombinant scFv against digoxin by phage display technology. Alirezapour, B; Omidfar, K; Rajabibazl, M; Rasaee, MJ, 2013)	1.35
"Digoxin is a commonly used medication for heart failure and cardiac arrhythmias that has recently been suggested as a novel chemotherapeutic agent. "	( Is digoxin use for cardiovascular disease associated with risk of prostate cancer? Hansten, PD; Stanford, JL; Wright, JL, 2014)	2.47
"Digoxin is a cardiac glycoside which, at high level, can indicate an increased risk of toxicity."	( An electrochemical immunosensor for digoxin using core-shell gold coated magnetic nanoparticles as labels. Ahmadi, A; Akbarzadeh, A; Omidfar, K; Pourbagher, N; Shirazi, H, 2014)	1.4
"Digoxin is an inexpensive agent and the totality of evidence indicates that it reduces hospitalizations and improves symptoms safely when dosed to achieve low serum concentrations."	( A perspective on re-evaluating digoxin's role in the current management of patients with chronic systolic heart failure: targeting serum concentration to reduce hospitalization and improve safety profile. Adams, KF; Bauman, JL; Butler, J; Ghali, JK; Herbert Patterson, J; Mackowiak, JI; Sabbah, H; Stough, WG; van Veldhuisen, DJ; Ventura, HO, 2014)	1.41
"Digoxin is a frequently prescribed drug, particularly in the elderly population, in which there is an increased prevalence of atrial fibrillation and cardiac failure. "	( Efficiency of individual dosage of digoxin with calculated concentration. Li, P; Qin, W; Wang, X; Yang, P; Zhang, X; Zhao, L, 2014)	2.12
"Digoxin is a widely used drug for ventricular rate control in patients with atrial fibrillation (AF), despite a scarcity of randomised trial data. "	( Digoxin use in patients with atrial fibrillation and adverse cardiovascular outcomes: a retrospective analysis of the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Berkowitz, SD; Breithardt, G; Califf, RM; Fox, KA; Halperin, JL; Hankey, GJ; Lokhnygina, Y; Mahaffey, KW; Nessel, CC; Patel, MR; Piccini, JP; Singer, DE; Stevens, SR; Washam, JB, 2015)	3.3
"Digoxin is a cardiac glycoside that is commonly used to treat heart failure. "	( Digoxin ameliorates autoimmune arthritis via suppression of Th17 differentiation. Baek, S; Cho, ML; Kwok, SK; Lee, DG; Lee, J; Park, MK; Park, SH, 2015)	3.3
"Digoxin is a frequently prescribed drug in the elderly population. "	( A New Method for Individualized Digoxin Dosing in Elderly Patients. Ardanuy Albajar, R; Calvo Hernández, MV; García González, D; Macías Núñez, JF; Martin-Suarez, A, 2016)	2.16
"Digoxin is a substrate of P-glycoprotein (P-gp) and organic anion transporting polypeptide transporters that are encoded by ABCB1 and SLCO1B3 genes. "	( ABCB1 and SLCO1B3 Gene Polymorphisms and Their Impact on Digoxin Pharmacokinetics in Atrial Fibrillation Patients among the Tunisian Population. Douki, W; Fredj, N; Grissa, MH; Hellara, I; Kerkeni, E; Monastiri, K; Mzali, M; Nouira, S; Sekma, A; Tounsi, N; Trabelsi, I, 2017)	2.14
"Digoxin is a cardiac glycoside that is frequently prescribed in atrial fibrillation and heart failure. "	( [A patient with severe digoxin toxicity]. Haak, MB; Kuypers, MI; van Bentum, R; van Keulen, K; van Rhee, KP, 2017)	2.21
"Digoxin is a commonly prescribed cardiac glycoside with a narrow therapeutic index. "	( Evaluation of the pharmacokinetics of digoxin in healthy subjects receiving etoricoxib. Agrawal, NG; De Smet, M; Gumbs, CP; Michiels, N; Musser, BJ; Schwartz, JI; Wagner, JA; Wehling, M, 2008)	2.06
"As digoxin is a P-glycoprotein substrate, the trial also explored the potential of deferasirox to alter the pharmacokinetics of compounds transported by P-glycoprotein in general."	( Absence of an effect of a single-dose deferasirox on the steady-state pharmacokinetics of digoxin. Balez, S; Belleli, R; Robeva, A; Sechaud, R, 2008)	1.08
"Digoxin is an inhibitor of the sodium-potassium ATPase. "	( The effects of intravenous calcium in patients with digoxin toxicity. Levine, M; Nikkanen, H; Pallin, DJ, 2011)	2.06
"Digoxin is an agent that is readily available, can be administered acutely and long-term, intravenously or orally, is safe and may be beneficial in both acute and chronic heart failure (HF)."	( Digoxin for the treatment of chronic and acute heart failure syndromes. Filippatos, GS; Gheorghiade, M; Harinstein, ME, 2009)	2.52
"Digoxin is a time-tested drug that accounts for 20 million drug prescriptions annually in the United States."	( Contemporary indications and therapeutic implications for digoxin use. Chockalingam, A; Chockalingam, P; Mittal, MK, 2011)	1.33
"Digoxin is an important therapeutic agent for the treatment of congestive cardiac failure. "	( Digoxin - a therapeutic agent and mechanistic probe: review of liquid chromatographic mass spectrometric methods and recent nuances in the clinical pharmacology attributes of digoxin. Ramesh, M; Srinivas, NR, 2009)	3.24
"Digoxin was found to be a weak substrate of organic anion-transporting polypeptide (OATP) 1B3 in transfected cells."	( Rifampin's acute inhibitory and chronic inductive drug interactions: experimental and model-based approaches to drug-drug interaction trial design. Cai, X; Chu, X; Ding, Y; Evers, R; Gibson, C; Reitman, ML; Roupe, K; Stoch, A; Stone, JA; Venkatasubramanian, R; Wagner, JA; Witter, R; Yabut, J; Zajic, S, 2011)	1.09
"Digoxin is an important medication for heart failure (HF) patients and sennosides are widely used to treat constipation. "	( Exposure to sennoside-digoxin interaction and risk of digoxin toxicity: a population-based nested case-control study. Chan, AL; Huang, TY; Lee, WJ; Leu, HB; Li, IH; Wang, MT, 2011)	2.13
"Digoxin is a phyto-estrogen capable of inducing hormonal effects. "	( Digoxin use and the risk of cancers of the corpus uteri, ovary and cervix. Biggar, RJ; Melbye, M; Wohlfahrt, J, 2012)	3.26
"Digoxin is a potent inhibitor of HIF-1α signaling pathway and blood vessel formation in C4-2 castration-resistant prostate tumors."	( Digoxin inhibits blood vessel density and HIF-1a expression in castration-resistant C4-2 xenograft prostate tumors. Gayed, BA; O'Malley, KJ; Pilch, J; Wang, Z, 2012)	3.26
"Digoxin is a pharmaceutical used in the control of cardiac dysfunction. "	( Anti-digoxin Fab variants generated by phage display. Kalil, J; Moro, AM; Murata, VM; Schmidt, MC; Tsuruta, LR, 2013)	2.35
"Digoxin is a cardiotonic glycoside that is primarily used in the treatment of heart failure, atrial fibrillation or flutter, and paroxysmal atrial tachycardia. "	( Report of a suicidal digoxin intoxication: a case report. Concheiro, L; López-Rivadulla, M; Muñoz, JI; Rico, R; Rodríguez-Calvo, MS; Suárez-Peñaranda, JM, 2002)	2.08
"Digoxin is a cardioactive drug with a narrow therapeutic range (0.8-1.9 ng/mL)."	( Effect of the traditional Chinese medicines Chan Su, Lu-Shen-Wan, Dan Shen, and Asian ginseng on serum digoxin measurement by Tina-quant (Roche) and Synchron LX system (Beckman) digoxin immunoassays. Chow, L; Dasgupta, A; Johnson, M; Wells, A, 2003)	1.26
"Digoxin is a steroidal glycoside and could be synthesised by the isoprenoid pathway."	( Studies on digoxin--14C-acetate incorporation in to digoxin and degenerative changes in the brain in rats administered digoxin. Augustine, J; Kurup, PA; Ravikumar, A, 2001)	1.42
"Digoxin is a cardiac glycoside that undergoes active secretion in the renal tubules by the MDR1 (P-glycoprotein) drug efflux pump."	( From bench to bedside: utilization of an in vitro model to predict potential drug-drug interactions in the kidney: the digoxin-mifepristone example. Ito, S; Koren, G; Woodland, C, 2003)	1.25
"Digoxin is a cardiac glycoside that is widely used for the treatment of congestive heart failure. "	( A rapid and sensitive LC/MS/MS assay for quantitative determination of digoxin in rat plasma. Chong, S; Morrison, RA; Yao, M; Zhang, H; Zhu, M, 2003)	1.99
"Digoxin is a commonly prescribed cardiac glycoside with a narrow therapeutic index."	( Voriconazole does not affect the steady-state pharmacokinetics of digoxin. Kleinermans, D; Nichols, D; Purkins, L; Wood, N, 2003)	1.28
"Digoxin is a popular cardiac glycoside with very narrow therapeutic range. "	( Lethal quercetin-digoxin interaction in pigs. Chao, PD; Hou, YC; Hsiu, SL; Wang, YH; Wen, KC, 2004)	2.11
"Digoxin is an agent with a long history of use in the management of heart failure; its benefits have just been quantified in recent years. "	( Digoxin in heart failure. Spencer, AP, 2003)	3.2
"Digoxin is a drug commonly used in geriatrics. "	( [Symptoms of severe digoxin intoxication in patients hospitalized in geriatric wards]. Chmielewski, Z; Jóźwiak, A; Rajska-Neumann, A; Wieczorowska-Tobis, K, 2004)	2.09
"Digoxin is a drug with a narrow therapeutic index, which is a substrate of the ATP-dependent efflux pump P-glycoprotein. "	( Characterisation of (R/S)-propafenone and its metabolites as substrates and inhibitors of P-glycoprotein. Bachmakov, I; Eichelbaum, M; Fromm, MF; Hofmann, U; Rekersbrink, S, 2005)	1.77
"Digoxin is a widely used drug in patients with congestive heart failure. "	( Comparison of target concentration intervention strategy with conventional dosing of digoxin. Anbalagan, M; Muralidharan, TR; Rajendran, SD; Rao, YM; Thanikachalam, S, )	1.8
"Digoxin is a substrate for Pgp, CYP3A, and Oatp2."	( Altered oral bioavailability and pharmacokinetics of P-glycoprotein substrates by coadministration of biochanin A. Cousineau, M; Danser, E; Dewire, R; Floden, J; Peng, SX; Ritchie, DM, 2006)	1.06
"Digoxin is a cardioactive drug with a narrow therapeutic range. "	( Therapeutic drug monitoring of digoxin: impact of endogenous and exogenous digoxin-like immunoreactive substances. Dasgupta, A, 2006)	2.06
"Digoxin is a well-known probe for the activity of P-glycoprotein. "	( Modelling the influence of MDR1 polymorphism on digoxin pharmacokinetic parameters. Becquemont, L; Comets, E; Jaillon, P; Lavielle, M; Mentré, F; Verstuyft, C, 2007)	2.04
"Digoxin is a known substrate of ATP-binding cassette B1 (ABCB1/MDR1). "	( Common ATP-binding cassette B1 variants are associated with increased digoxin serum concentration. Aarnoudse, AJ; Arp, PP; Dieleman, JP; Hofman, A; Molokhia, M; Stricker, BH; Uitterlinden, AG; van der Heiden, IP; van Schaik, RH; Visser, LE, 2008)	2.02
"Digoxin is a commonly prescribed medication for a variety of cardiovascular abnormalities. "	( Perspectives on digoxin absorption from small bowel resections. Kumer, KP; Nwangwu, JT; Nwangwu, PU, 1983)	2.05
"Digoxin continues to be an important cause of drug toxicity. "	( Activated charcoal increases digoxin elimination in patients. Abad, F; Carcas, AJ; Frias, J; Ibañez, C, 1995)	2.03
"Digoxin toxicity is a potentially life-threatening condition."	( Digoxin toxicity. Recognizing the varied visual presentations. Lance, SE; Leeper, HF; Piltz, JR; Slamovits, T; Wertenbaker, C, 1993)	2.45
"Digoxin is a toxic drug with a narrow therapeutic index that is mostly used by the elderly. "	( [Digoxin poisoning in patients of 2 geriatric departments in London: prevalence and mortality]. Collas, D; Hoefnagels, WH; Rai, GS; van Asselt, DZ, 1993)	2.64
"Digoxin intoxication is a common problem in the elderly. "	( Advances in the management of digoxin toxicity in the older patient. Bismuth, C; Borron, SW; Muszynski, J, 1997)	2.03
"Digoxin intoxication is a serious medical problem, and impairment of renal function is a common risk factor for toxicity. "	( Digoxin intoxication in a patient with end-stage renal disease: efficacy of digoxin-specific Fab antibody fragments and peritoneal dialysis. Caraco, Y; Caspi, O; Gotsman, O; Wolf, DG; Zylber-Katz, E, 1997)	3.18
"Digoxin is a known inhibitor of sodium/potassium adenosine triphosphatase (sodium pump), a plasma membrane enzyme that has a role in the regulation of smooth muscle tone."	( A possible mechanism for alteration of human erectile function by digoxin: inhibition of corpus cavernosum sodium/potassium adenosine triphosphatase activity. Daley, J; Daller, M; Gholami, S; Goldstein, I; Gupta, S; Krane, RJ; Saenz de Tejada, I; Salimpour, P; Traish, AM, 1998)	1.26
"Digoxin toxicity is a major public health issue in the United States. "	( Coadministration of digoxin with itraconazole in renal transplant recipients. Friedman, GS; Mathis, AS, 2001)	2.08
"Digoxin is a cardiac glycoside used in the treatment of congestive heart failure."	( Cysteine-free mutant of aequorin as a photolabel in immunoassay development. Daunert, S; Deo, SK; Paeng, IR; Shrestha, S, )	0.85
"Digoxin is a widely used drug. "	( [Evaluation of the use of digoxin in a primary care emergency service]. Campodarve, I; Ibáñez, J; Knobel, H; Nogués, J; Ortiz, P; Serrat, R, 1991)	2.02
"Digoxin is an important drug in the treatment of patients with either congestive heart failure or atrial arrhythmia. "	( Making digoxin therapeutic drug monitoring more effective. Matzuk, MM; Shaw, LM; Shlomchik, M, 1991)	2.18

Effects

Digoxin has a function of vagus nervous system stimulation. Digoxin-Fab has a mean plasma half-life of 19-30 h and a Vd of 0.4 L/kg.

Digoxin has been a controversial drug since its introduction >200 years ago. Digoxin use has long been recognized to affect adversely male sexual function but the underlying mechanism is poorly understood.

Excerpt	Reference	Relevance
"Digoxin has a narrow therapeutic range."	( Digoxin therapeutic drug monitoring: age influence and adverse events. Ben Sassi, M; Charfi, R; Daghfous, R; Gaies, E; Jebabli, N; Trabelsi, S, 2020)	2.72
"Digoxin has a function of vagus nervous system stimulation."	( The Effect of Autoantibody against M2-Muscarinic Acetylcholine Receptor in Heart Failure Patients on Digoxin Treatment. Fan, Z; Hou, D; Liu, J; Ma, G; Wang, H; Wang, X; Xu, L; Xu, X; Zhang, J; Zhang, L; Zhang, Z, 2018)	1.42
"Digoxin-Fab has a mean plasma half-life of 19-30 h and a Vd of 0.4 L/kg."	( Digoxin-specific antibody fragments in the treatment of digoxin toxicity. Buckley, NA; Chan, BS, )	2.3
"Digoxin has a narrow therapeutic index and is primarily renally eliminated. "	( Discordant results from "real-world" patient samples assayed for digoxin. Jones, TE; Morris, RG, 2008)	2.03
"Digoxin has a narrow therapeutic margin and potentially life-threatening cardiac adverse effects. "	( Digoxin: serious drug interactions. , 2010)	3.25
"2. Digoxin--which has a steroid character--caused faulty imprinting by treatments at the 15th, 17th and 20th days of pregnancy."	( Fetal digoxin treatment enhances the binding capacity of thymic glucocorticoid receptors in adult female rats. Csaba, G; Inczefi-Gonda, A, 1998)	1.29
"Digoxin, which has a very narrow therapeutic window, is one of the most commonly prescribed drugs in the treatment of congestive heart failure. "	( P-glycoprotein system as a determinant of drug interactions: the case of digoxin-verapamil. Beijnen, JH; Koks, CH; Schellens, JH; Verschraagen, M, 1999)	1.98
"Digoxin has a narrow therapeutic:toxic ratio and concentrations are affected by a number of drugs."	( Heart failure: to digitalise or not? The view against. White, HD, 1992)	1
"Digoxin has been associated with reduced interstage mortality for patients with functional single ventricles with aortic hypoplasia or ductal-dependent systemic circulation. "	( Digoxin Associated With Greater Transplant-Free Survival in High- vs Low-Risk Interstage Patients. Anderson, JB; Bates, KE; Brown, DW; Brown, TN; Lannon, CM; Tweddell, JS, 2022)	3.61
"Digoxin use has increased significantly but remains variable between different hospitals, independent of case-mix."	( Attributable mortality benefit of digoxin treatment in hypoplastic left heart syndrome after the Norwood operation: An instrumental variable-based analysis using data from the Pediatric Health Information Systems Database. Gardner, MM; Glatz, AC; Goldberg, D; Huang, J; Lemley, B; O'Byrne, ML; Ravishankar, C; Rome, JJ; Song, L, 2023)	1.91
"Digoxin has a narrow therapeutic range."	( Digoxin therapeutic drug monitoring: age influence and adverse events. Ben Sassi, M; Charfi, R; Daghfous, R; Gaies, E; Jebabli, N; Trabelsi, S, 2020)	2.72
"Digoxin treatment has come under scrutiny in recent years after reports from several studies that it is associated with increased mortality in patients with atrial fibrillation (AF). "	( Modified SAMe-TT Çanga, Y; Emre, A; Eren, S; Güzelburç, Ö; Karataş, MB; Yelgeç, NS; Zengin, A, 2021)	2.06
"Digoxin has been used extensively for decades in the treatment of heart failure and arrhythmias despite some controversies over its benefit. "	( Association of digoxin therapy with case fatality rate in acute pulmonary embolism. Çanga, Y; Emre, A; Karataş, MB; Yelgeç, NS; Zengin, A, 2021)	2.42
"Digoxin has been demonstrated to restore iodide uptake capacity in vitro in poorly differentiated and anaplastic NMTC cells, termed redifferentiation."	( Digoxin treatment reactivates in vivo radioactive iodide uptake and correlates with favorable clinical outcome in non-medullary thyroid cancer. Corver, WE; Crezee, T; Kimura, S; Kuiper, JG; Morreau, J; Nagarajah, J; Netea-Maier, RT; Plantinga, TS; Pritchard, C; Smit, JWA; Tesselaar, MH; van Engen-van Grunsven, I, 2021)	2.79
"Digoxin has been associated with lower interstage mortality (ISM) following stage 1 palliation (S1P). "	( Impact of Digoxin Use on Interstage Outcomes of Single Ventricle Heart Disease (From a NPC-QIC Registry Analysis). Brown, T; Godown, J; Hill, GD; Klausner, RE; Kohl, K; Minich, L; Parra, D, 2021)	2.47
"Digoxin use has been shown to be associated with a lower risk of 30-day all-cause hospital readmissions in older patients with heart failure (HF). "	( Digoxin and 30-Day All-Cause Readmission in Long-Term Care Residents Hospitalized for Heart Failure. Ahmed, A; Allman, RM; Anker, SD; Aronow, WS; Arundel, C; Blackman, MR; Butler, J; Deedwania, P; Fletcher, RD; Fonarow, GC; Love, TE; Morgan, C; Panjrath, G; Sheriff, HM; Thogaripally, MR; Zeng, Q, 2017)	3.34
"Digoxin has been shown to reduce heart failure hospitalizations with a neutral effect on mortality. "	( Digoxin Benefit Varies by Risk of Heart Failure Hospitalization: Applying the Tufts MC HF Risk Model. Kent, DM; Konstam, MA; Upshaw, JN; van Klaveren, D, 2018)	3.37
"Digoxin use has been associated with a lower risk of 30-day all-cause admission and readmission in patients with heart failure and reduced ejection fraction (HFrEF)."	( Digoxin use and lower risk of 30-day all-cause readmission in older patients with heart failure and reduced ejection fraction receiving β-blockers. Ahmed, A; Allman, RM; Aronow, WS; Arundel, C; Bhyan, P; Dooley, DJ; Fonarow, GC; Lam, PH; Mohammed, SF; Morgan, CJ; Sheriff, HM; Waagstein, F, 2018)	3.37
"Digoxin has been associated with reduced interstage mortality after Norwood procedure. "	( Digoxin Use in Infants with Single Ventricle Physiology: Secondary Analysis of the Pediatric Heart Network Infant Single Ventricle Trial Public Use Dataset. Burch, PT; Lambert, LM; Menon, SC; Minich, LL; Sheng, X; Truong, DT; Williams, RV, 2018)	3.37
"Digoxin has a function of vagus nervous system stimulation."	( The Effect of Autoantibody against M2-Muscarinic Acetylcholine Receptor in Heart Failure Patients on Digoxin Treatment. Fan, Z; Hou, D; Liu, J; Ma, G; Wang, H; Wang, X; Xu, L; Xu, X; Zhang, J; Zhang, L; Zhang, Z, 2018)	1.42
"Digoxin has been used for more than 50 years in patients with Atrial Fibrillation (AF), with the goal of Controlling Heart Rate (HR) and restoring sinus rhythm. "	( Digoxin in Atrial Fibrillation: An Old Topic Revisited. Ferrari, F; Santander, IRMF; Stein, R, 2020)	3.44
"Digoxin has 60-80% bioavailability, a mean plasma half-life of 40 h and a volume of distribution (Vd) of 5-10 L/kg and low protein binding (20%)."	( Digoxin-specific antibody fragments in the treatment of digoxin toxicity. Buckley, NA; Chan, BS, )	2.3
"Digoxin has been shown to have an estrogenic effect and is associated with increased risk of gynecomastia and estrogen-sensitive cancers such as breast and uterus cancer. "	( Digoxin use after diagnosis of breast cancer and survival: a population-based cohort study. Cardwell, CR; Hughes, CM; Karasneh, RA; Mc Menamin, ÚC; Murray, LJ, 2015)	3.3
"Digoxin has antitumor activity for retinoblastoma while exerting antiangiogenic activity in vitro at similar concentrations. "	( Pharmacokinetics, Safety, and Efficacy of Intravitreal Digoxin in Preclinical Models for Retinoblastoma. Abramson, D; Arana, E; Buitrago, E; Chantada, GL; Croxatto, JO; Del Sole, MJ; Djaballah, H; Francis, J; Laurent, V; Mena, HA; Negrotto, S; Schaiquevich, P; Sgroi, M; Winter, U, 2015)	2.11
"Digoxin has been a key therapeutic for heart failure and atrial tachyarrhythmias for over 200 years following Withering's groundbreaking work depicting the therapeutic benefit of the common botanical foxglove in his 1785 monograph. "	( Digoxin: its role in contemporary medicine. Goldberger, ZD; Stucky, MA, 2015)	3.3
"Digoxin has long been used in the treatment of heart failure and has been shown to inhibit the proliferation of cancer cells through multiple pathways."	( Digoxin inhibits PDGF-BB-induced VSMC proliferation and migration through an increase in ILK signaling and attenuates neointima formation following carotid injury. Gu, Y; Hu, S; Ma, G; Qiao, Y; Tang, C; Wang, D; Wang, Q; Yan, G, 2015)	2.58
"Digoxin has been shown to affect a number of pathways that are of relevance to cancer, and its use has been associated with increased risks of breast and uterus cancer and, more recently, a 40% increase in colorectal cancer risk. "	( Digoxin use after diagnosis of colorectal cancer and survival: a population-based cohort study. Cardwell, CR; Hughes, CM; Karasneh, RA; Murray, LJ, 2015)	3.3
"Digoxin has class IIa recommendations for treating HF with reduced ejection fraction (HFrEF) in the United States. "	( Temporal Trends of Digoxin Use in Patients Hospitalized With Heart Failure: Analysis From the American Heart Association Get With The Guidelines-Heart Failure Registry. Bhatt, DL; Butler, J; Fonarow, GC; Hernandez, AF; Ju, C; Macon, C; Patel, N; Schulte, PJ; Thadani, U; Yancy, CW, 2016)	2.21
"Digoxin has long been used for rate control in atrial fibrillation (AF); its safety remains controversial.We performed a literature search using MEDLINE (source PubMed, January 1, 1966, to July 31, 2015) and EMBASE (January 1, 1980, to July 31, 2015) with no restrictions. "	( Digoxin Use and Adverse Outcomes in Patients With Atrial Fibrillation. Cheng, YJ; Li, ZY; Liu, ZH; Zeng, WT; Zhang, M, 2016)	3.32
"Digoxin has been used during the acute phase of ST elevation myocardial infarction (STEMI) complicated with AF or heart failure."	( Digoxin and short term mortality after acute STEMI: Results from the MAGIC trial. Charnigo, R; Darrat, Y; Delisle, B; Di Biase, L; Elayi, CS; Metawee, M; Morales, G; Natale, A; Sorrell, V, 2016)	2.6
"Digoxin has a narrow therapeutic index and is primarily renally eliminated. "	( Discordant results from "real-world" patient samples assayed for digoxin. Jones, TE; Morris, RG, 2008)	2.03
"Digoxin has been reported to increase chemoreflex sensitivity in humans."	( Digoxin increases peripheral chemosensitivity and the ventilatory response to exercise in normal subjects. Adamopoulos, D; Beloka, S; Deboeck, G; Janssen, C; Lheureux, O; Naeije, R; van de Borne, P, 2010)	2.52
"Digoxin has been shown to reduce heart failure (HF) hospitalizations with no overall effect on mortality in HF patients. "	( Digoxin treatment in heart failure--unveiling risk by cluster analysis of DIG data. Ather, S; Blaustein, A; Bozkurt, B; Deswal, A; Divakaran, VG; Giorgberidze, I; Mann, DL; Peterson, LE; Ramasubbu, K; Wehrens, XH, 2011)	3.25
"Digoxin has a narrow therapeutic margin and potentially life-threatening cardiac adverse effects. "	( Digoxin: serious drug interactions. , 2010)	3.25
"Digoxin has been used as an inotropic agent in heart failure for a long time. "	( Characterization of the mechanisms of the increase in PPARδ expression induced by digoxin in the heart using the H9c2 cell line. Chen, LJ; Chen, ZC; Cheng, JT; Cheng, KC; Lin, HJ; Yu, BC, 2011)	2.04
"Digoxin has been reported to improve symptoms and reduce hospitalization in patients with heart failure as well as to control rapid ventricular rate in patients with atrial fibrillation. "	( Use of digoxin for heart failure and atrial fibrillation in elderly patients. Cheng, JW; Rybak, I, 2010)	2.26
"Digoxin has been used for hundreds of years to aid rate control in atrial fibrillation and as a positive inotrope in heart failure. "	( Digoxin - time to take the gloves off? Cooper, R; Eade, E; Mitchell, AR, 2013)	3.28
"Digoxin has also been described as a substrate of various organic anion-transporting polypeptide (OATP) transporters, posing a risk that inhibition of OATPs may result in a clinically relevant DDI similar to what has been observed for P-gp."	( Digoxin is not a substrate for organic anion-transporting polypeptide transporters OATP1A2, OATP1B1, OATP1B3, and OATP2B1 but is a substrate for a sodium-dependent transporter expressed in HEK293 cells. Chen, L; Ellens, H; Hirakawa, B; Jani, M; Lee, CA; Mease, K; Reyner, EL; Sane, RS; Taub, ME; Watson, CA, 2011)	2.53
"Digoxin has at least 2-compartment behavior."	( Some comments and suggestions concerning population pharmacokinetic modeling, especially of digoxin, and its relation to clinical therapy. Jelliffe, RW, 2012)	1.32
"Digoxin therapy has no effect on mortality in heart failure. "	( Digoxin in heart failure and cardiac arrhythmias. Campbell, TJ; MacDonald, PS, 2003)	3.2
"Digoxin-specific Fab has been shown to neutralize an endogenous Na+/K+ ATPase inhibitor (endogenous digoxin-like Na+/K+ ATPase regulatory factor; EDLF) in rats and humans and to lower blood pressure."	( Characterization of the neutralizing activity of digoxin-specific Fab toward ouabain-like steroids. Brooks, DP; Edwards, RM; Pullen, MA, 2004)	1.3
"Digoxin has been evaluated as a therapy to increase the effectiveness of calcium in severe calcium channel antagonist overdoses."	( Dose-dependent hemodynamic effect of digoxin therapy in severe verapamil toxicity. Almond, G; Bania, TC; Chu, J; Perez, E, 2004)	1.32
"Digoxin has been used to treat congestive heart failure (CHF) for more than two centuries. "	( Digoxin may reduce the mortality rates in patients with congestive heart failure. Song, S; Wang, L, 2005)	3.21
"Anti-digoxin Fab fragments have been used successfully for many years in the management of severe poisoning with digoxin, digitoxin, and a range of other structurally related compounds, including cardiotoxins from Nerium and Thevetia sp."	( Fab antibody fragments: some applications in clinical toxicology. Flanagan, RJ; Jones, AL, 2004)	0.78
"Digoxin has traditionally been the drug of choice for ventricular rate control in patients with chronic atrial fibrillation (AF), with or without heart failure (HF) with systolic dysfunction. "	( The safety of digoxin as a pharmacological treatment of atrial fibrillation. Caballero, R; Delpón, E; Tamargo, J, 2006)	2.14
"Digoxin use has decreased significantly from 31.4% in late 2001 to 23.5% in late 2004 (P < .00001) independent of patient age, gender, or baseline creatinine."	( Digoxin use and digoxin toxicity in the post-DIG trial era. Hauptman, PJ; Hussain, Z; Swindle, J, 2006)	2.5
"Digoxin therapy has long been used to treat heart failure; however, its effectiveness was not completely known until recently. "	( Digoxin therapy for heart failure: an update. Hatcher, HF; Morris, SA; Reddy, DK, 2006)	3.22
"Digoxin has been the cornerstone of the treatment of heart failure for more than 2 centuries. "	( Is digoxin a drug of the past? Dickinson, MG; Pervaiz, MH; Yamani, M, 2006)	2.4
"Digoxin has been reported to induce feminizing effects in man. "	( Digoxin does not alter plasma steroid levels in health men. Kley, HK; Krüskemper, HL; Müller, A; Peerenboom, H, 1982)	3.15
"Digoxin therapy has been made more rational by the measurement of serum digoxin concentrations. "	( Erythrocyte Na+, K+-ATPase and serum digoxin concentrations. Ahmed, K; From, AH; Quarfoth, GJ; Steele, BW, 1983)	1.98
"Digoxin has been successfully used to treat fetal supraventricular tachycardia. "	( Fetal supraventricular tachycardia: in utero therapy with digoxin and quinidine. Flinn, GS; Marin-Garcia, J; Shaver, DC; Sibai, BM; Spinnato, JA; Watson, DL, 1984)	1.95
"Digoxin kinetics have been studied in hyperthyroid and 8 euthyroid patients after a single oral and i.v."	( [Serum levels and kinetics of digoxin in patients with hyperthyroidism (author's transl)]. Bocchiardo, M; Brossa, C; Brusca, A; Gaita, F; Molinatti, GM; Rosettani, E, 1980)	1.27
"Digoxin has not been shown to affect the natural history of heart failure and should be reserved for patients who remain symptomatic after treatment with ACE inhibitors and diuretics."	( Management of heart failure. I. Pharmacologic treatment. Baker, DW; Bottorff, M; Konstam, MA; Pitt, B, 1994)	1.01
"Digoxin has been a traditional therapy in heart failure, but methodologic limitations in earlier studies have prevented definitive conclusions regarding its efficacy."	( Randomized study assessing the effect of digoxin withdrawal in patients with mild to moderate chronic congestive heart failure: results of the PROVED trial. PROVED Investigative Group. Harrison, MC; Jolly, MK; Shahidi, FE; Uretsky, BF; Yellen, LG; Young, JB, 1993)	1.99
"Digoxin therapy has been suggested to increase mortality risk in survivors of acute myocardial infarction. "	( Digoxin and increased mortality among patients recovering from acute myocardial infarction: importance of digoxin dose. The SPRINT Study Group. Behar, S; Boyko, V; Goldbourt, U; Kaplinsky, E; Leor, J; Rabinowitz, B; Reicher-Reiss, H, 1995)	3.18
"Digoxin has been the traditional first drug of choice for CHF, but with protracted controversy about its efficacy and safety."	( [Pharmacologic treatment of chronic congestive heart failure]. Halawa, B, 1996)	1.02
"Digoxin has been a controversial drug since its introduction >200 years ago. "	( Value of digoxin in heart failure and sinus rhythm: new features of an old drug? de Graeff, PA; Lie, KI; Remme, WJ; van Veldhuisen, DJ, 1996)	2.15
"Digoxin has also been shown in several clinical trials to reduce the need for rehospitalization in CHF patients."	( Economics of treating heart failure. Mark, DB, 1997)	1.02
"Digoxin use has long been recognized to affect adversely male sexual function but the underlying mechanism is poorly understood. "	( A possible mechanism for alteration of human erectile function by digoxin: inhibition of corpus cavernosum sodium/potassium adenosine triphosphatase activity. Daley, J; Daller, M; Gholami, S; Goldstein, I; Gupta, S; Krane, RJ; Saenz de Tejada, I; Salimpour, P; Traish, AM, 1998)	1.98
"2. Digoxin--which has a steroid character--caused faulty imprinting by treatments at the 15th, 17th and 20th days of pregnancy."	( Fetal digoxin treatment enhances the binding capacity of thymic glucocorticoid receptors in adult female rats. Csaba, G; Inczefi-Gonda, A, 1998)	1.29
"Digoxin, which has a very narrow therapeutic window, is one of the most commonly prescribed drugs in the treatment of congestive heart failure. "	( P-glycoprotein system as a determinant of drug interactions: the case of digoxin-verapamil. Beijnen, JH; Koks, CH; Schellens, JH; Verschraagen, M, 1999)	1.98
"Digoxin has been an effective treatment for fetal supraventricular tachycardia (SVT), but second-line therapy remains more controversial. "	( Second-line treatment of fetal supraventricular tachycardia using flecainide acetate. Cordes, TM; Darragh, RK; Ebenroth, ES, )	1.57
"Digoxin-assay has to be available as an "emergency-measure", since the early diagnosis of digitalis intoxication in old patients is often very difficult because of the ambiguous clinical picture."	( [Serum glycoside level in old age. Problems of course control in glycoside therapy]. Schwarzfischer, VP, 1976)	0.98
"Digoxin has less potency than the calcium antagonists or beta-blocking drugs with respect to atrioventricular nodal blockade."	( Redefining the role of digoxin in the treatment of atrial fibrillation. Marchlinski, FE; Sarter, BH, 1992)	1.32
"Digoxin has a narrow therapeutic:toxic ratio and concentrations are affected by a number of drugs."	( Heart failure: to digitalise or not? The view against. White, HD, 1992)	1
"Digoxin has also been proposed as a treatment for terminating recent-onset atrial fibrillation, for maintaining sinus rhythm after an episode of atrial fibrillation, and as prophylactic therapy in patients with paroxysmal atrial fibrillation to prevent excessive tachycardia during a paroxysm."	( Digoxin for atrial fibrillation: a drug whose time has gone? Falk, RH; Leavitt, JI, 1991)	2.45
"Digoxin intoxication has been reported to be a common adverse drug reaction with an in-hospital incidence of 6% to 23% and an associated mortality rate as high as 41%. "	( The evolving pattern of digoxin intoxication: observations at a large urban hospital from 1980 to 1988. Battilana, G; Gheorghiade, M; Goldstein, S; Mahdyoon, H; Rosman, H, 1990)	2.03
"Digoxin has the potential to be harmful in patients with ischemic heart disease."	( Digoxin--a redundant drug in congestive cardiac failure. Poole-Wilson, PA; Robinson, K, 1989)	2.44
"Anti-digoxin Fab fragments have been approved by the Food and Drug Administration for the treatment of digitalis intoxication."	( Immunological approach to poisoning. Brizgys, M; Rollins, DE, 1986)	0.73
"Digoxin has been associated with a variety of drug interactions. "	( Prazosin alters free and total plasma digoxin levels in dogs. Gokhale, RD; Plunkett, LM; Tackett, RL; Vallner, JJ, 1985)	1.98

Actions

Digoxin and ASI-222 produce different profiles of changes in cardiac autonomic nerve activity. Digoxin produced an increase in pulmonary vascular resistance (66.1%) and pulmonary arterial pressure (8.2 mm Hg) at 70 min after injection in a blood-perfused lung preparation.

Excerpt	Reference	Relevance
"Digoxin could suppress the pulmonary fibrosis in mice induced by bleomycin, which might be associated with the regulation of fibroblast activation via suppressing PI3K/Akt signaling pathway in a dose-dependent manner."	( [Digoxin alleviates pulmonary fibrosis by regulating phosphatidylinositol-3-kinase/Akt signaling through inhibiting the activation of fibroblast: an in vivo and in vitro experiment]. Bai, Y; Jia, L; Mei, X; Tian, X; Yang, M; Zhao, P, 2022)	3.07
"Digoxin plays a potential anti-tumor role in breast cancer in vitro, possibly by inducing mitochondria-dependent apoptosis."	( Anti-proliferative effect of digoxin on breast cancer cells via inducing apoptosis. Han, XC; Hu, WN; Niu, FL; Yan, JY; Zhang, JH; Zhao, YT, 2017)	2.19
"Digoxin use may lower this risk in patients with heart failure with reduced ejection fraction (HFrEF), but data on contemporary patients receiving other evidence-based therapies are lacking."	( Digoxin Use and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction. Abdelmawgoud, A; Ahmed, A; Allman, RM; Bayoumi, E; Fonarow, GC; Kanonidis, IE; Lam, PH; Malik, A; Morgan, CJ; Packer, M; Qamer, SZ; Singh, S, 2019)	2.68
"Digoxin was found to inhibit the proliferation of A549 cells under hypoxic conditions."	( Digoxin downregulates NDRG1 and VEGF through the inhibition of HIF-1α under hypoxic conditions in human lung adenocarcinoma A549 cells. Gao, H; Li, D; Li, H; Peng, JJ; Tan, Y; Wei, D; Zhang, T, 2013)	2.55
"Digoxin and DLIF inhibit the release of proinflammatory cytokines from PBMC via NF-K: B-dependent pathway suggesting an anti-inflammatory effect."	( Digoxin and digoxin-like immunoreactive factors (DLIF) modulate the release of pro-inflammatory cytokines. de Leon, R; Espinosa, R; Ihenetu, K; Perez-Pinero, A; Planas, G; Waldbeser, L, 2008)	3.23
"Digoxin did not cause a clinically significant change in the dynamic parameters during both periods."	( Pharmacokinetic and pharmaceutic interaction between digoxin and Cremophor RH40. Burhenne, J; Ding, R; Haefeli, WE; Hoppe-Tichy, T; Mikus, G; Riedel, KD; Tayrouz, Y; Weiss, J, 2003)	1.29
"Digoxin plays a part in healing of congestive heart failure in clinic. "	( [Analysis of detecting methods of digoxin blood drug level]. Li, HF; Li, YX; Mao, JY, 2007)	2.06
"Digoxin was found to increase heart rate variability, especially those measures of heart rate variability thought to represent parasympathetic activity."	( Effects of digoxin on time domain measures of heart rate variability in patients with stable chronic cardiac failure: withdrawal and comparison group studies. Flapan, AD; Francis, CM; Goodfield, NE; Neilson, JM; Wright, RA, 1997)	1.41
"Digoxin produced an increase in both SMVR and IGSR throughout the 30 to 120 minute period of the study in thirteen dogs despite the presence of severe grades of SMA stenosis."	( Digoxin induced intestinal vasoconstriction. The effects of proximal arterial stenosis and glucagon administration. Bynum, TE; HANLEY, HG; Levinsky, RA; Lewis, RM, 1975)	2.42
"Digoxin levels were lower in patients with coronary heart disease (1.71 +/- 0,22 ng/ml; n = 16) than in patients with right ventricle overload (2.94 +/- 0,74 mg/ml; n + 7 - p less than 0.05)."	( [Blood digoxin and treatment of heart failure in aged patients]. Hatt, PY; Jouannot, P; Lavabre, J; Thomas, M, 1976)	1.43
"Digoxin failed to inhibit estradiol binding to the receptor protein in vitro."	( Mechanism of interaction of digitalis with estradiol binding sites in rat uteri. Loriaux, DL; Pita, JC; Rifka, SM, 1976)	0.98
"Digoxin recovery was lower after early (62.1 +/- 5.3%) than after late (86.9 +/- 7.7%) proximal administration but inulin recovery was complete (99.6 +/- 2.7%) after all injections."	( Renal tubular transport of 3H-digoxin in saline diuresis in rats. Kauker, ML; Roman, RJ, 1976)	1.27
"Digoxin caused an increase in end-diastolic pressure in myopathic and chronic alcohol hearts but not control hearts."	( Activation of glycolysis with isoproterenol but not digoxin reverses chronic alcohol depression in hamster hearts. Auffermann, W; Buser, P; Parmley, WW; Wikman-Coffelt, J; Wu, S, 1992)	1.26
"Digoxin excess can produce characteristic bradyarrhythmias, tachyarrhythmias, and hyperkalemia. "	( Which cardiac disturbances should be treated with digoxin immune Fab (ovine) antibody? Callans, DJ; Hook, BG; Marchlinski, FE, 1991)	1.98
"Digoxin and ASI-222 produce different profiles of changes in cardiac autonomic nerve activity and appear to differ in autonomic reflex receptor interactions."	( Different patterns of autonomic nerve activity produced by a polar vs. a neutral cardiac glycoside. Caldwell, RW; Rebagay, WR, 1990)	1
"Digoxin produced an increase in pulmonary vascular resistance (66.1%) and pulmonary arterial pressure (8.2 mm Hg) at 70 min after injection in the constant-flow, blood-perfused lung preparation."	( Mechanism of the pulmonary vasoconstrictor action of digoxin in the dog. Caldwell, RW; Elam, JT; Mecca, TE, )	1.1
"Digoxin therapy can cause important toxic events when elevated drug levels occur. "	( Falsely elevated digoxin levels: another look. Longley, JM; Murphy, JE, 1989)	2.06
"The digoxin-induced increase in sodium concentration was significantly higher than that observed for chloride."	( Influence of digoxin and diuretic therapy on sweat fluid composition. Aladjem, M; Benzon, L; Mor, A, 1985)	1.12
"Digoxin provoked an increase in systolic blood pressure and splanchnic vascular resistance."	( Effect of calcium antagonists on basal and digitalis-dependent changes in splanchnic and systemic hemodynamics. Eichler, HG; Gasić, S; Korn, A, 1987)	0.99

Treatment

Digoxin treatment has come under scrutiny in recent years after reports from several studies that it is associated with increased mortality in patients with atrial fibrillation (AF) Digoxin is a safe treatment for management of fetal tachyarrhythmias.

Excerpt	Reference	Relevance
"Digoxin treatment was classified as adequate or inadequate."	( Factors associated with unjustified chronic treatment with digoxin in patients with acute heart failure and relationship with short-term prognosis. Alquézar-Arbé, A; Flores-Quesada, S; Gil, V; Herrero, P; Jacob, J; Llorens, P; Martín-Mojarro, E; Miró, Ò; Sánchez, C; Troiano-Ungerer, OJ, 2023)	1.87
"Digoxin treatment has come under scrutiny in recent years after reports from several studies that it is associated with increased mortality in patients with atrial fibrillation (AF). "	( Modified SAMe-TT Çanga, Y; Emre, A; Eren, S; Güzelburç, Ö; Karataş, MB; Yelgeç, NS; Zengin, A, 2021)	2.06
"Digoxin is a safe treatment for management of fetal tachyarrhythmias. "	( Maternal effects induced by oral digoxin during treatment of fetal tachyarrhythmia: Case series and literature review. Antiñolo, G; Chimenea, Á; García-Díaz, L; Méndez, A, 2021)	2.35
"Digoxin treated calves demonstrated reduced signs of clinical illness after BRSV infection, and reduced lung pathology compared to untreated control calves."	( Prophylactic digoxin treatment reduces IL-17 production in vivo in the neonatal calf and moderates RSV-associated disease. Guerra-Maupome, M; McGill, JL; Schneider, S, 2019)	1.6
"Digoxin treatment significantly lowered mPAP, reduced WT% and WA% and right ventricular hypertrophy compared with those of the hypoxic group (mPAP: (27.3 ± 2.7) vs (38.5 ± 2.3) mmHg (1 mmHg = 0.133 kPa); RV/(LV+S): (30.9 ± 3.3)% vs (42.8 ± 2.6)%, WT%: (21.7 ± 3.6)% vs (39.3 ± 2.0)%; WA%: (56.3 ± 4.7)% vs (79.5 ± 5.7)%, all P < 0.05). "	( [Effects of early digoxin treatment on hypoxia-induced pulmonary artery hypertension]. Gu, Y; Hu, S; Ma, G; Qiao, Y; Tang, C; Wang, D; Wang, J; Wang, Q; Yan, G, 2014)	2.18
"Digoxin treatment was associated with a significant increase in all-cause mortality, vascular death, and sudden death in patients with AF. "	( Digoxin use in patients with atrial fibrillation and adverse cardiovascular outcomes: a retrospective analysis of the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Berkowitz, SD; Breithardt, G; Califf, RM; Fox, KA; Halperin, JL; Hankey, GJ; Lokhnygina, Y; Mahaffey, KW; Nessel, CC; Patel, MR; Piccini, JP; Singer, DE; Stevens, SR; Washam, JB, 2015)	3.3
"Digoxin treatment suppressed the incidence of arthritis and joint inflammation in mice with CIA."	( Digoxin ameliorates autoimmune arthritis via suppression of Th17 differentiation. Baek, S; Cho, ML; Kwok, SK; Lee, DG; Lee, J; Park, MK; Park, SH, 2015)	2.58
"Digoxin treatment is associated with an absolute risk increase of 19 (95% CI 13-26) additional deaths from any cause per 1000 person-years.Digoxin use is associated with a significant increased risk for death from any cause in patients with AF."	( Digoxin Use and Adverse Outcomes in Patients With Atrial Fibrillation. Cheng, YJ; Li, ZY; Liu, ZH; Zeng, WT; Zhang, M, 2016)	2.6
"Digoxin treatment also induced dose-dependent vision loss monitored by ERG on naïve mice without induction of EAU."	( Digoxin Inhibits Induction of Experimental Autoimmune Uveitis in Mice, but Causes Severe Retinal Degeneration. Gery, I; Hinshaw, SJ; Li, Y; Lyu, C; Ogbeifun, O; Qian, H; Shi, G; Wandu, WS, 2016)	2.6
"Digoxin treatment produced a significant decrease in cerebral infarct size and reversal of I/R induced impairment of memory and motor incoordination."	( Studies on cerebral protection of digoxin against ischemia/reperfusion injury in mice. Jaggi, AS; Kaur, S; Rehni, AK; Singh, N, 2009)	1.35
"Digoxin treatment resulted in an increase of intracellular [Na(+)]."	( High-content screening of drug-induced cardiotoxicity using quantitative single cell imaging cytometry on microfluidic device. Han, E; Kim, MJ; Lee, SC; Pal, S; Song, JM, 2011)	1.09
"Digoxin treatment resulted in a higher conversion rate in non-hydropic fetuses with fetal tachyarrhythmias than in hydropic fetuses (p < 0.001)."	( Review of diagnosis, treatment, and outcome of fetal atrial flutter compared with supraventricular tachycardia. Gembruch, U; Katalinic, A; Kohl, T; Krapp, M; Sharland, GK; Simpson, JM, 2003)	1.04
"Digoxin treatment is common in acute ischaemic stroke, the intended patient population for NXY-059."	( Effect of NXY-059, a novel neuroprotectant, on the pharmacokinetics of a single dose of digoxin in healthy subjects. Borgå, O; Cheng, YF; Huledal, G; Kågedal, M; Nilsson, D; Reinholdsson, I; Svensson, H; van Hout, M, 2007)	1.28
"Digoxin treatment tended to return the changes in the index of myocardial contractility and cardiac function, intracellular Ca++, Na+, K+, extracellular space, and sarcolemmal Na+-K+-ATPase of the failing heart toward control levels."	( Effects of chronic digoxin treatment on cardiac function, electrolytes, and sarcolemmal ATPase in the canine failing heart due to chronic mitral regurgitation. Bharadwaj, B; O'Neil, CL; Prasad, K, 1984)	1.32
"The digoxin treatment taken at home was continued in hospital."	( The day-to-day variation in serum digoxin concentration. The Hørsholm digoxin study. Hartling, L; Ovesen, J; Serup, J, 1983)	1.03
"Digoxin pretreatment afforded no protection."	( Verapamil, propranolol, and hydralazine protect against the acute cardiac depression induced by adriamycin. Parmley, WW; Rapcsak, M; Rouleau, JL; Sievers, R; Wikman-Coffelt, J, 1983)	0.99
"Both digoxin-treated and control rats demonstrated significant age-related increments in digoxin uptake."	( Maturation of renal tubular transport of digoxin. Aladjem, M; Halkin, H; Kaplinsky, C; Laufer, Y; Wolfish, N, 1981)	0.98
"Digoxin-treated patients received a 1-mg intravenous loading in the first 24 to 36 hours, then 0.125 to 0.25 mg orally daily for 1 month."	( Effects of diltiazem versus digoxin on dysrhythmias and cardiac function after pneumonectomy. Amar, D; Bains, MS; Burt, ME; Downey, RJ; Ginsberg, RJ; Leung, DH; Roistacher, N; Rusch, VW, 1997)	1.31
"Digoxin-treated patients had a similar incidence of all SVD (31%) as concurrent controls (11 of 40 patients [28%])."	( Effects of diltiazem versus digoxin on dysrhythmias and cardiac function after pneumonectomy. Amar, D; Bains, MS; Burt, ME; Downey, RJ; Ginsberg, RJ; Leung, DH; Roistacher, N; Rusch, VW, 1997)	1.31
"Digoxin-treated patients had significantly lower oxidative enzyme activity than patients without digoxin treatment."	( Skeletal muscle alterations in patients with chronic heart failure. Eriksson, BO; Grimby, G; Held, P; Schaufelberger, M; Swedberg, K, 1997)	1.02
"Digoxin treatment significantly decreased heart rate (HR) and diastolic blood pressure (DBP) during the overnight sleeping phase of day 10 compared with placebo (HR, 4 beats min-1; DBP, 8 mmHg; P < 0.05). "	( Effects of digoxin and digitoxin on circadian blood pressure profile in healthy volunteers. Grossmann, M; Jamieson, MJ; Kirch, W, 1998)	2.13
"Digoxin pretreatment did not increase digoxin uptake."	( Induction of digoxin-like material production, and the digoxin binding in the unicellular organism Tetrahymena by digitoxin. Csaba, G; Kovács, P; Müller, WE, 1998)	1.39
"Digoxin pretreatment (125 microg/kg, i/p) did not affect the time spent in the water-associated compartment (476+/-80 sec), but prevented the acquisition of ethanol CPP (385+/-112 sec in ethanol-paired side, P<0.05)."	( Involvement of endogenous digitalis-like factors in voluntary selection of alcohol by rats. Bagrov, AY; Bagrov, YY; Dmitrieva, NI; Manusova, NB; Patkina, NA; Zvartau, EE, 1999)	1.02
"The digoxin treatment was discontinued during the observation period."	( Cardiac arrhythmias, electrolytes, and digoxin concentration in plasma and urine in patients treated with digoxin. Bertler, A; Monti, M; Ohlin, P; Redfors, A, 1975)	1
"In digoxin treated compared to control rats no differences between individual phosphatides were noted in any of the tissues examined whereas in guinea pigs the same comparison revealed differences in 8 instances, 4 of which were in LPC."	( Cardiac glycoside effects on rat and guinea pig phospholipids. Fritz, PJ, 1975)	0.77
"Digoxin pretreatment for 14 d did not significantly change the chronotropic or depressor responses to isoprenaline in anaesthetised dogs but there was a 10-fold increase in inotropic sensitivity to isoprenaline following withdrawal."	( Increased sensitivity to isoprenaline following digoxin pretreatment in anaesthetised and conscious dogs. Einstein, R; Gray, P; Hunyor, SN; Jones, MP; Mihailidou, AS; Richardson, DP, 1990)	1.26
"The digoxin-treated group exhibited higher plasma levels of norepinephrine compared with control dogs."	( Mechanism of the pulmonary vasoconstrictor action of digoxin in the dog. Caldwell, RW; Elam, JT; Mecca, TE, )	0.86
"In digoxin-treated patients, the result was 94% of that obtained in control subjects (P less than 0.005)."	( Measurement of circulating sodium-pump inhibitory activity in uraemia and essential hypertension. Boutagy, J; Marwood, JF; Monaghan, J; Stokes, GS; Willcocks, D, 1986)	0.78
"Digoxin treatment increased ejection fraction (4.4% increase) compared with captopril therapy (1.8% increase) and placebo (0.9% increase)."	( Comparative effects of therapy with captopril and digoxin in patients with mild to moderate heart failure. The Captopril-Digoxin Multicenter Research Group. , )	1.11
"Digoxin treatment consisted of 0.6 mg kg-1 given i.v."	( Digoxin-induced cardiac toxicity in the anaesthetized guinea-pigs and effect of heparin infusion. Abacioğlu, N; Cakici, I; Demiryürek, AT; Dörtlemez, H; Kanzik, I, 1987)	2.44
"Digoxin-treated animals experienced a worse survival rate than did controls (19 of 50 versus 33 of 50; P less than .01)."	( Digoxin disrupts the inflammatory response in experimental pneumococcal pneumonia. Esposito, AL, 1985)	2.43
"Treatment of digoxin rescued changes in glymphatic transport, white matter structure, and cognitive function."	( Digoxin Ameliorates Glymphatic Transport and Cognitive Impairment in a Mouse Model of Chronic Cerebral Hypoperfusion. Cao, J; Guo, X; Hao, J; Li, J; Li, R; Luo, X; Pan, D; Wang, M; Wang, W; Xie, M; Yao, D; Yu, Z, 2022)	2.52
"Treatment with digoxin was associated with a neutral effect on all-cause mortality (HR 1.04, 95 % CI 0.91-1.20, I2 = 57.9 %), all-cause hospitalization (HR 0.97, 95 % CI 0.88-1.07, I2 = 0.0 %), HFhospitalization (HR 0.96, 95 % CI 0.90-1.02, I2 = 41.4 %), and all-cause mortality or HFhospitalization (HR 1.07, 95 % CI 0.91-1.26, I2 = 81.2 %)."	( Digoxin and Outcomes in Patients with Heart Failure and Preserved Ejection Fraction (HFpEF) Patients: A Systematic Review and Meta- Analysis. Aghajanloo, A; Arasteh, O; Ghavami, V; Hashemi-Shahri, SH; Mohammadpour, AH; Reiner, Ž; Sahebkar, A, 2023)	2.69
"Treatment with digoxin was associated with superior 1-year transplant-free survival in unadjusted analyses (85% vs 82%, P = .02)."	( Attributable mortality benefit of digoxin treatment in hypoplastic left heart syndrome after the Norwood operation: An instrumental variable-based analysis using data from the Pediatric Health Information Systems Database. Gardner, MM; Glatz, AC; Goldberg, D; Huang, J; Lemley, B; O'Byrne, ML; Ravishankar, C; Rome, JJ; Song, L, 2023)	1.53
"Treatment with Digoxin and oxygen resulted in a progressive 71% reduction in peak systolic ductal gradient, improved right ventricular function, and decreased tricuspid regurgitation."	( Management of fetal ductus arteriosus constriction with Digoxin and oxygen therapy. Lanni, SM; Naqvi, AZ; Rosenthal, JB, 2020)	1.14
"Treatment with digoxin was associated with an increased mortality risk in the subgroup of patients with AF (n = 627,620, HR 1.23, 95% CI, 1.17 to 1.30, p <0.01), and in the subgroup of patients with HF (n = 197,441, HR 1.11, 95% CI, 1.06 to 1.16, p<0.01)."	( Meta-Analysis of Effects of Digoxin on Survival in Patients with Atrial Fibrillation or Heart Failure: An Update. Benz, AP; Erath, JW; Hohnloser, SH; Lopes, RD; Vamos, M, 2019)	1.15
"Treatment with digoxin inhibited the development of EAU, as well as the cellular response to IRBP. "	( Digoxin Inhibits Induction of Experimental Autoimmune Uveitis in Mice, but Causes Severe Retinal Degeneration. Gery, I; Hinshaw, SJ; Li, Y; Lyu, C; Ogbeifun, O; Qian, H; Shi, G; Wandu, WS, 2016)	2.23
"Treatment with digoxin might selectively improve cognitive performance among older patients with HF."	( Digoxin and cognitive performance in patients with heart failure: a cohort, pharmacoepidemiological survey. Bernabei, R; Cocchi, A; Laudisio, A; Marzetti, E; Pagano, F; Zuccalà, G, 2009)	2.15
"Treatment with digoxin should be used cautiously in such patients because of risk for adverse outcomes."	( Digoxin therapy does not improve outcomes in patients with advanced heart failure on contemporary medical therapy. Agha, SA; Butler, J; Georgiopoulou, VV; Giamouzis, G; Kalogeropoulos, AP; Laskar, S; Rashad, MA; Smith, AL; Waheed, S, 2009)	2.14
"Treatment with digoxin has no proven value in infants solely affected with RDS."	( Digoxin for preventing or treating neonatal respiratory distress syndrome. Ozek, E; Soll, R, 2011)	2.15
"Pretreatment with digoxin modifies these responses."	( The neonatal but not the mature heart adapts to acute tachycardia by beneficial modification of the force-frequency relationship. Bøtker, HE; Gross, GJ; Hjortdal, VE; Khambadkone, S; Redington, AN; Schmidt, MR; Sørensen, KE; Vogel, M; White, PA, 2011)	0.69
"Treatment with digoxin attenuated the development of right ventricle (RV) hypertrophy and prevented the pulmonary vascular remodeling and increases in PASMC [Ca(2+)](i), pH, and RV pressure that occur in mice exposed to chronic hypoxia."	( Digoxin inhibits development of hypoxic pulmonary hypertension in mice. Abud, EM; Maylor, J; Myers, AC; Punjabi, A; Semenza, GL; Shimoda, LA; Sylvester, JT; Undem, C; Zaiman, AL, 2012)	2.16
"Mice treated with digoxin showed lower cholesterol and higher ubiquinone content in their hearts, and a small increase in their serum HDL (high-density lipoprotein) cholesterol."	( Digoxin and ouabain induce the efflux of cholesterol via liver X receptor signalling and the synthesis of ATP in cardiomyocytes. Bosia, A; Campia, I; Caruso, D; Costamagna, C; Crepaldi, T; Ghigo, D; Kopecka, J; Leo, C; Mitro, N; Pescarmona, G; Riganti, C; Sala, V, 2012)	2.15
"Treatment with digoxin significantly prolonged cardiac allograft survival compared with dimethyl sulfoxide treatment (mean survival time, 16.5±2.2 versus 8.1±0.7 days; P<0.01). "	( Digoxin attenuates acute cardiac allograft rejection by antagonizing RORγt activity. Chen, W; Li, J; Wang, S; Wang, W; Wu, J; Xia, J; Xie, A; Ye, P; Zhou, C, 2013)	2.19
"Pretreatment with digoxin caused a significant (P <.001) ST depression in precordial leads, which was similar in men and women and returned promptly to the isoelectric level after exercise resulting in a counterclockwise rotation of the ST/HR loop."	( The effect of digoxin on the electrocardiogram of healthy middle-aged and elderly patients at rest and during exercise--a comparison with the ECG reaction induced by myocardial ischemia. Jogestrand, T; Nowak, J; Sundqvist, K, 2002)	1
"Treatment with digoxin and flecainide was successful; the heart rate returned to sinus rhythm within one day, and fetal hydrops resolved within 8 days of treatment."	( Fetal supraventricular tachycardia diagnosed and treated at 13 weeks of gestation: a case report. Anteby, EY; Hamani, Y; Porat, S; Yagel, S, 2003)	0.66
"Treatment with digoxin-specific antibody fragments relieved the signs and symptoms of intoxication within a few hours."	( Digitoxin intoxication with severe thrombocytopenia: reversal by digoxin-specific antibodies. Hess, T; Riesen, W; Scholtysik, G; Stucki, P, 1983)	0.84
"Treatment with digoxin was associated with a 50-70% increase in the RBC Na+ concentration, whereas the RBC K+ concentration decreased by 7-10%."	( The kinetics of red blood cell electrolyte alterations following digoxin administration. A report of two pediatric cases. Lock, JE; Loes, MW; Mirkin, BL; Singh, S, 1981)	0.84
"Treatment with digoxin-specific Fab fragments resulted in transient clinical and ECG improvement."	( Treatment of foxglove extract poisoning with digoxin-specific Fab fragments. Libera, JM; Locke, RJ; Rich, SA, 1993)	0.89
"The treatment with digoxin should be individualised."	( Does digoxin still have a role in congestive heart failure? Kothari, SS, )	0.96
"Treatment with digoxin has no proven value in infants solely affected with respiratory distress syndrome."	( Digoxin for preventing or treating neonatal respiratory distress syndrome. Soll, RF, 2000)	2.09
"Treatment with digoxin and furosemide alleviated clinical signs for approximately 10 months."	( Congestive heart failure associated with myxomatous degeneration of the left atrioventricular valve in a parakeet. Lehmkuhl, L; Oglesbee, BL, 2001)	0.65
"3. Treatment with digoxin, thyroxine or both produced a similar significant increase in the amount of Na+ + K+ -dependent adenosine triphosphatase in liver without an additive effect."	( Rat hepatic sodium plus potassium ion-dependent adenosine triphosphatase after treatment with digoxin and thyroxine. Lindsay, R; Parker, JL, 1976)	0.8
"The treatment of digoxin intoxication has been revolutionized by digoxin specific antibody fragments (Fab). "	( Influence of assay methods on serum concentrations of digoxin during FAB fragment treatment. Bach, P; Banner, W; Burk, B; Freestone, S; Gooch, WM, 1992)	0.87
"Treatment with digoxin-immune antibody fragments (FAB) promptly lead to abolition of the ventricular arrhythmia and disappearance of every clinical symptoms in hours."	( [Severe poisoning with digitalis treated by the administration of anti-digoxin antibodies]. Casillas Villamor, A; Delgado Jiménez, JF; Gómez Pajuelo, C; Sáenz de la Calzada, C, 1991)	0.85
"Treatment with digoxin increased, whereas treatment with ouabain decreased, the growth rate of Tetrahymena, but the progeny generations showed an increased mitotic rate after both treatments. "	( Digoxin effect and imprinting in the unicellular Tetrahymena. Csaba, G; Darvas, Z; Swydan, R, 1986)	2.07
"Pre-treatment with digoxin had no effect on the acute peripheral vascular responses to frusemide and failed to inhibit the acute increases in plasma renin activity and plasma aldosterone produced by frusemide."	( The effects of propranolol and digoxin on the acute vascular responses to frusemide in normal man. Finch, MB; Johnston, GD; Leahey, WJ; Nicholls, DP; O'Connor, PC, 1985)	0.87
"Pretreatment with digoxin did not significantly influence the concentration-dependent contractile responses to 5-hydroxytryptamine and prostaglandin F2 alpha (PGF2 alpha)."	( Digoxin inhibition of relaxation induced by prostacyclin and vasoactive intestinal polypeptide in small human placental arteries. Andersson, KE; Forman, A; Maigaard, S, )	1.9

Toxicity

TCP was safe for patients with a digoxin overdose complicated by symptomatic bradycardia and should be recommended in such situations. Withdrawal of digoxin from toxic patients led to improved colour vision.

Excerpt	Reference	Relevance
" Toxic doses of digoxin cause marked hyperthermia in both the acute and chronic groups."	( Toxicity of digoxin in acutely and chronically heat-exposed rats. Hovevey-Sion, D; Kaplanski, J, 1979)	0.98
"Twenty-nine patients with gynaecological cancers who received over 400 mg of doxorubicin were monitored electrocardiographically to determine whether cardiac glycosides countered the adverse effects of high total doses of doxorubicin."	( Doxorubicin cardiotoxicity: possible role of digoxin in its prevention. Gibson, AL; Guthrie, D, 1977)	0.52
" In all cases in which suspicion of digitalis intoxication was raised, serum digoxin measurements could discriminate between the toxic and the nontoxic patients."	( Serum digoxin and empiric methods in identification of digitoxicity. Buch, J; Waldorff, S, 1978)	0.97
" The mean plasma digoxin concentration in clinically toxic patients was significantly higher than the mean concentration in non-toxic patients."	( Monitoring digoxin therapy. The use of plasma digoxin concentration measurements in the diagnosis of digoxin toxicity. Aronson, JK; Grahame-Smith, DG; Wigley, FM, 1978)	0.99
" To elucidate further the role of the CNS in digitalis-induced arrhythmias, the inotropic and toxic effects of a highly polar semisynthetic cardiac glycoside, 3beta-O-(4 amino-4,6 dideoxy-beta-D-galactopyranosyl)-digitoxigenin (ASI-222) were compared to those of digoxin and correlated with plasma and cerebrospinal fluid (CSF) concentrations of each drug."	( Inotropic and toxic effects of a polar cardiac glycoside derivative in the dog. Greenblatt, DJ; Lloyd, BL; Mudge, GH; Smith, TW, 1978)	0.44
" Calculated was the toxic concentration of digoxin as that concentration which caused arrest of the preparation."	( Influence of frequency of stimulation on the toxicity of digoxin on isolated guinea-pig atria in different extracellular Ca2+. Bremhorst, T; Schümann, HJ; Wagner, J, 1978)	0.77
" The concentration of digoxin which caused standstill is defined as the toxic one."	( Calcium-dependent toxic effects of digoxin in isolated myocardial preparations. Salzer, WW; Wagner, J, 1976)	0.85
"1 The tendency of a given oral dose of digoxin to induce cardiac dysrhythmia was determined indirectly at various times after its administration to eight conscious dogs by measurement of the intravenous dose of acetylstrophanthidin necessary to induce toxic changes in the ECG."	( The relationship between cardiotoxicity and plasma digoxin concentration in conscious dogs. Chapple, DJ; Hughes, R; Johnson, BF, 1976)	0.78
"It is generally accepted that the sensitivity to toxic effects of digitalis increases with advancing age; however, the relative contribution of pharmacokinetics and pharmacodynamics to this aging-related change is presently unknown."	( Digoxin cardiotoxicity in aging anesthetized F344 rats. Kennedy, RH; Ruch, S; Seifen, E, 1992)	1.73
" While the clinical syndrome of digoxin toxicity is well understood, how toxic manifestations change with age is not known."	( Lack of age-related differences in the clinical presentation of digoxin toxicity. Ettinger, WH; Furberg, CD; Hickey, AR; Wofford, JL, 1992)	0.81
" The proportion of subjects with nausea/vomiting as a toxic manifestation did not consistently change with age (42%, 48%, 48%, and 46%, respectively)."	( Lack of age-related differences in the clinical presentation of digoxin toxicity. Ettinger, WH; Furberg, CD; Hickey, AR; Wofford, JL, 1992)	0.52
" It has been found that highly toxic doses of the drugs produced no changes in the cell multiplication of normal human fibroblasts."	( [The cytotoxicity of strophanthin G and digoxin]. Narimanov, AA, )	0.4
" This article reviews the developmental basis for digoxin disposition and its pharmacological and toxic effects."	( Age-related differences in digoxin toxicity and its treatment. Kearns, GL; Wells, TG; Young, RA, )	0.68
" Sotalol is an effective, safe drug for the treatment of supraventricular tachycardias in early infancy."	( Efficacy and safety of oral sotalol in early infancy. Sandor, G; Tipple, M, 1991)	0.28
" There were fewer reports of adverse effects, and no clinically significant episodes of hyperkalemia or renal impairment on ramipril."	( A comparison of the efficacy and safety of ramipril and digoxin added to maintenance diuretic treatment in patients with chronic heart failure. Brown, JJ; Kennedy, JA; Kesson, E; Kholeif, MA; Lorimer, AR; Murray, G; Pringle, S; Stock, JK, 1991)	0.53
" Treatment with Fab fragments reduces the probability of dying more for the seriously toxic than for the less seriously toxic patient."	( Cost-effectiveness analysis of the use of digoxin immune Fab (ovine) for treatment of digoxin toxicity. Mauskopf, JA; Wenger, TL, 1991)	0.55
" The drug has a narrow therapeutic range and has gained a reputation for producing adverse effects in older patients."	( Digoxin toxicity in the aged. Characterising and avoiding the problem. Johnston, GD; Passmore, AP, )	1.57
" The results rather suggest that long-term treatment with ibopamine affords an increase in survival and a delay in the progression of the disease, without adverse effects on cardiac rhythm and myocardial oxygen balance, and with a general improvement in the patients' quality of life."	( Safety of ibopamine therapy in congestive heart failure. Ibopamine cohort study: baseline and 1-year results. Cesana, B; Ferrari, V; Licciardello, L; Sher, D; Sirtori, F, 1991)	0.28
"The influence of digoxin on the systemic toxic effects of bupivacaine was studied in a rodent animal model."	( Digoxin enhances bupivacaine toxicity in rats. De Kock, M; Gautier, P; Renotte, MT; Vandewalle, F, )	1.91
" A total of 215 patients experienced posttreatment adverse events."	( Digoxin Immune Fab therapy in the management of digitalis intoxication: safety and efficacy results of an observational surveillance study. Carpenter, VP; Furberg, CD; Hickey, AR; Hlatky, MA; Kirkpatrick, CH; Smith, TW; Strauss, HC; Tilson, HH; Wenger, TL, 1991)	1.72
"The combined use of digoxin and quinidine has been associated with potentially fatal toxic reactions."	( Quinidine enhancement of digoxin toxicity in rats and minipigs. Hanig, JP; Thompson, TJ, 1989)	0.9
"A prospective study to correlate clinical digoxin toxicity with serum digoxin levels was carried out in 67 patients of whom 24 were clinically toxic and 43 were asymptomatic."	( Digoxin toxicity: clinical and laboratory assessment. Ch'ng, SL; Chandrasekharan, N; Masduki, A; Ong, HT, 1989)	1.98
"This study examined effects of extracellular magnesium (Mg++0) on the positive inotropic and toxic actions of cardiotonic steroids in cardiac muscle isolated from guinea pig heart."	( Extracellular magnesium and cardiotonic steroid toxicity in isolated myocardial preparations. Kafiluddi, R; Kennedy, RH; Seifen, E, 1989)	0.28
" Unlike those reported in younger patients, all but one of the adverse drug reactions occurred 8 h or more after the first dose."	( Evaluation of the safety of enalapril in the treatment of heart failure in the very old. Bowes, SG; Denham, MJ; Dobbs, RJ; Dobbs, SM; Hunt, WB; O'Neill, CJ; Royston, JP; Sullens, CM, 1988)	0.27
"Digitalis glycosides have a narrow margin between therapeutic and toxic levels."	( Digitalis toxicity: mechanisms, diagnosis, and management. Bhatia, SJ; Smith, TW, 1987)	0.27
"Effects of amiloride on the inotropic and toxic actions of cardiac glycosides were examined using left atrial muscle isolated from guinea pig heart."	( Suppression of positive inotropic and toxic effects of cardiac glycosides by amiloride. Akera, T; Brody, TM; Kennedy, RH, 1985)	0.27
"The narrow margin between the therapeutic and toxic doses and serum levels of cardiac glycosides results in a high incidence of digitalis toxicity."	( New advances in the assessment and treatment of digitalis toxicity. Smith, TW, 1985)	0.27
"The time course of the reversal of toxic and nontoxic effects of digoxin by digoxin-specific antibody fragments (Fab) was measured in isolated human ventricular myocardium."	( Reversal of toxic and non-toxic effects of digoxin by digoxin-specific Fab fragments in isolated human ventricular myocardium. Erdmann, E; Näbauer, M, 1987)	0.77
"Monensin is extremely toxic to some domestic animals, like the equine species, if they ingest poultry or cattle rations containing the drug."	( Effects of some calcium modulators on monensin toxicity. Martin, T; Mitema, ES; Sangiah, S, 1988)	0.27
" Continued therapy with digoxin combined with diltiazem 240 mg/day for 21 +/- 8 days in nine patients showed persistent effect on heart rate and blood pressure without any toxic manifestations or change in serum digoxin (1."	( Efficacy and safety of medium- and high-dose diltiazem alone and in combination with digoxin for control of heart rate at rest and during exercise in patients with chronic atrial fibrillation. Cohen, J; Elkayam, U; Harrison, E; Mitani, G; Rahimtoola, SH; Roth, A, 1986)	0.8
" The results of this study suggest that the in vitro tests employed can be useful as screening tests for local toxic effect of intramuscular drug preparations."	( Tests for local toxicity of intramuscular drug preparations: comparison of in vivo and in vitro methods. Bagdon, RE; Højelse, F; Svendsen, O, 1985)	0.27
"The effects of hypoxia on the tolerance of myocardium to the toxic actions of digitalis were studied in isolated heart muscle preparations."	( Effects of myocardial hypoxia on digitalis-induced toxicity in the isolated heart of guinea pigs and cats. Akera, T; Kim, DH, 1984)	0.27
"01) in the guinea-pig and LD50 was 30."	( Comparison of digoxin-induced cardiac toxicity in resistant and sensitive species. Kaplanski, J; Posner, J; Weinhouse, E, 1983)	0.63
" Practolol did not alter the toxic dose of ASI-254 and produced little change in the pattern of cardiotoxicity; both control and practolol-treated dogs died in cardiac standstill."	( Effect of cardiac beta-adrenergic blockade or denervation on cardiotoxicity of digoxin and an aminosugar cardenolide. Caldwell, RW; Nash, CB; Puryear, SK, )	0.36
"), a selective alpha-2 agonist, enhanced the toxic effects of digoxin by decreasing both the arrhythmogenic and lethal dose of digoxin."	( Central alpha receptors and their role in digoxin cardiotoxicity. Plunkett, LM; Tackett, RL, 1983)	0.77
" Only 3 patients complained of adverse effects from verapamil during the double-blind phase of the study."	( Effectiveness and safety of oral verapamil to control exercise-induced tachycardia in patients with atrial fibrillation receiving digitalis. Baessler, C; Morganroth, J; Panidis, IP, 1983)	0.27
"There is a narrow difference between the therapeutic and toxic ranges of cardiac glycosides."	( Digitalis toxicity in infants and children. Chow-Tung, E; Hastreiter, AR; van der Horst, RL, )	0.13
" However, ventricular arrhythmias in dogs with A-V block presented similarities both in occurrence and spreading with the development of oscillatory afterpotentials (OAPs) and rhythmical triggered activity demonstrated in isolated digitalis-poisoned Purkinje fibers and ventricular myocardium: the repetitive discharge of toxic foci masked normal idioventricular pacemakers and was interrupted by variable pauses followed by the resumption of either a very slow idioventricular rhythm or a toxic focus."	( Digoxin-induced toxicity and experimental atrioventricular block in dogs. Relation between ventricular arrhythmias and oscillatory afterpotentials. Adamantidis, MM; Dupuis, BA; Duriez, PR; Vincent, AC, )	1.57
" Withdrawal of digoxin from toxic patients led to improved colour vision."	( The use of colour vision measurement in the diagnosis of digoxin toxicity. Aronson, JK; Ford, AR, 1980)	0.86
" Adverse reactions rates up to 20% had been observed in hospitalized patients."	( [Incidence of side effects in digitalis therapy]. Flasch, H, 1982)	0.26
" This mechanism may contribute to subnormal, prolonged cone-mediated ERG responses in retinal toxic reactions from cardiac glycosides."	( Digoxin retinal toxicity. Clinical and electrophysiological evaluation of a cone dysfunction syndrome. Shults, WT; Weleber, RG, 1981)	1.71
"Toxicity to digoxin was monitored in 437 consecutive recipients in a comprehensive drug surveillance programme, Adverse reactions developed in 19."	( The changing pattern of toxicity of digoxin. Henry, DA; Lawson, DA; Lowe, JM; Whiting, B, 1981)	0.92
"01), and LD50 in adults was 30."	( Cardiac toxicity of digoxin in newborn and adult rats. Danon, A; Gorodischer, R; Kaplanski, J; Warszawski, D; Weinhouse, E, 1980)	0.58
"In a prospective symptom-oriented study, patients with (n = 81) or without (n = 206) digoxin toxicity were not discernible on their serum digoxin concentration (SDC) because of a large overlap between toxic and non-toxic groups."	( Is the determination of serum digoxin concentration useful for the diagnosis of digitalis toxicity? Erdmann, E; Krawietz, W; Vogt, W; von Arnim, T, 1980)	0.77
"First, a patient who experienced toxic side effects from digoxin was studied acutely by serial electroretinography and later during convalescence."	( Electrophysiologic and electroretinographic evidence for photoreceptor dysfunction as a toxic effect of digoxin. Johnson, MA; Madreperla, SA; Nakatani, K, 1994)	0.75
"Reversible rod and cone dysfunction occur during exposure to toxic levels of digoxin."	( Electrophysiologic and electroretinographic evidence for photoreceptor dysfunction as a toxic effect of digoxin. Johnson, MA; Madreperla, SA; Nakatani, K, 1994)	0.73
"The influence of the immunoreactive endogenous digoxin-like factor (IEDLF) on the systemic toxic effects of bupivacaine was studied in a rodent model."	( The endogenous digoxin-like factor enhances bupivacaine toxicity in rats. DeKock, M; Gautier, P; Henin, D, )	0.74
" Threshold doses of bupivacaine's toxic effects (first ventricular arrhythmia, first seizure activity, 25% fall of baseline heart rate, 25% of baseline mean arterial blood pressure, isoelectric electroencephalogram) were significantly lower for the rats with an endogenous digoxin-like activity."	( The endogenous digoxin-like factor enhances bupivacaine toxicity in rats. DeKock, M; Gautier, P; Henin, D, )	0.66
" Thus, beta blockade may prove to be a safe and cost-effective bridge to transplantation."	( Safety and efficacy of beta blockade in patients with chronic congestive heart failure awaiting transplantation. Buchholz, C; Courtney, M; Gass, A; Kalman, J; Kukin, ML; Lansman, S; Steinmetz, M, )	0.13
"A clinical-laboratory analysis was carried out in 18 patients on long-term treatment with digoxin in whom toxic arrhythmia occurred, taking into account serum digoxin level measurement."	( [Digoxin level as a limited drug toxicity indicator in the assessment of post-digitalis arrhythmia]. Hoffmann, A; Jankowski, A; Marzec, A; Sinkiewicz, W, )	1.26
" The other 37 patients tolerated the high digoxin levels without exhibiting toxic effect."	( Relationship between high serum digoxin levels and toxicity. Catalyurek, H; Guven, H; Hazan, E; Kalkan, S; Oto, O; Tuncok, Y, 1997)	0.84
" Digoxin, warfarin, and clarithromycin were discontinued and the patient was admitted to the hospital for treatment to resolve the symptoms and to return laboratory values to a safe range."	( Concomitant digoxin toxicity and warfarin interaction in a patient receiving clarithromycin. Bolli, P; Fernandez, PG; Gooderham, MJ, )	1.42
" Forty-one toxic and 58 nontoxic patients were included."	( Digoxin level and clinical manifestations as determinants in the diagnosis of digoxin toxicity. Abad-Santos, F; Carcas, AJ; Frías, J; Ibáñez, C, 2000)	1.75
" On the basis of the limited systemic absorption and the absence of clinically significant cardiac or clotting effects, intra-amniotically administered digoxin may be considered safe for use before late second-trimester pregnancy terminations."	( Safety of intra-amniotic digoxin administration before late second-trimester abortion by dilation and evacuation. Benowitz, NL; Darney, PD; Drey, EA; Goldschlager, N; Thomas, LJ, 2000)	0.81
" Patients had ECG monitoring for 48 hours, and time of reversion, adequacy of rate control, and numbers of adverse events were compared."	( A prospective, randomized controlled trial comparing the efficacy and safety of sotalol, amiodarone, and digoxin for the reversion of new-onset atrial fibrillation. Joseph, AP; Ward, MR, 2000)	0.52
" There were also fewer adverse events in the active treatment group compared with the rate control group."	( A prospective, randomized controlled trial comparing the efficacy and safety of sotalol, amiodarone, and digoxin for the reversion of new-onset atrial fibrillation. Joseph, AP; Ward, MR, 2000)	0.52
"Herbal dietary supplements are often considered by patients to be safe and free from side effects."	( Digoxin toxicity in a 26-year-old woman taking a herbal dietary supplement. Scheinost, ME, 2001)	1.75
" Six subjects experienced adverse events while receiving placebo and seven while on tamsulosin."	( Effects of the concomitant administration of tamsulosin (0.8 mg) on the pharmacokinetic and safety profile of intravenous digoxin (Lanoxin) in normal healthy subjects: a placebo-controlled evaluation. Forrest, A; Ito, Y; Kamimura, H; Miyazawa, Y; Paul Starkey, L; Schentag, JJ; Swarz, H, 2002)	0.52
" This report alerts physicians to the need to be aware of a new community toxic exposure, as prompt treatment with digoxin specific Fab fragment may be life saving."	( Toad venom poisoning: resemblance to digoxin toxicity and therapeutic implications. Cohen, RA; Gowda, RM; Khan, IA, 2003)	0.8
"Automated clinical decision support (CDS) has shown promise in improving safe medication use."	( A trial of automated safety alerts for inpatient digoxin use with computerized physician order entry. DiDomenico, RJ; Galanter, WL; Polikaitis, A, )	0.39
"Overall, the alerts improved the safe use of digoxin."	( A trial of automated safety alerts for inpatient digoxin use with computerized physician order entry. DiDomenico, RJ; Galanter, WL; Polikaitis, A, )	0.65
"TCP was safe for patients with a digoxin overdose complicated by symptomatic bradycardia and should be recommended in such situations."	( Safety of transvenous temporary cardiac pacing in patients with accidental digoxin overdose and symptomatic bradycardia. Chen, JH; Chen, JY; Lin, LJ; Liu, PY, 2004)	0.83
"This pilot study sought to determine if the administration of calcium chloride when compared to normal saline would affect time to death when given to hyperkalemic, digoxin toxic swine."	( The effect of calcium chloride in treating hyperkalemia due to acute digoxin toxicity in a porcine model. Brewer, K; Hack, JB; Lewis, DE; Meggs, WJ; Woody, JH, 2004)	0.75
"25 mg/kg was determined to be appropriately toxic for this study."	( The effect of calcium chloride in treating hyperkalemia due to acute digoxin toxicity in a porcine model. Brewer, K; Hack, JB; Lewis, DE; Meggs, WJ; Woody, JH, 2004)	0.56
" A toxic digoxin level returned, Digoxin-specific antibody fragments (Digibind, Fab) were administered, and all signs and symptoms of toxicity resolved."	( Digoxin toxicity: pediatric survival after asystolic arrest. Carroll, LS; Eyal, D; Molczan, KA, 2005)	2.19
" All patients were assessed with 24-hour ECG monitoring, a maximal symptom-limited cardiopulmonary exercise test and evaluation of adverse events."	( Efficacy and safety of oral amiodarone in controlling heart rate in patients with persistent atrial fibrillation who have undergone digitalisation. Igoumenidis, NE; Kafarakis, PK; Kanoupakis, EM; Kochiadakis, GE; Mavrakis, HE; Vardas, PE, )	0.13
" Only a few randomised, controlled studies have evaluated the adverse effects of digoxin in patients with AF in a systematic way and side effects requiring drug withdrawal have rarely been reported."	( The safety of digoxin as a pharmacological treatment of atrial fibrillation. Caballero, R; Delpón, E; Tamargo, J, 2006)	0.92
" This drug interaction-determined as probable according to the Naranjo adverse drug reaction probability scale-may be mediated by P-glycoprotein."	( Telithromycin-induced digoxin toxicity and electrocardiographic changes. Laberge, P; Nenciu, LM; Thirion, DJ, 2006)	0.65
"We used data from a large heart failure registry to examine digoxin use at the time of hospital admission for heart failure, a surveillance system for recording toxic drug exposures to describe patterns in digoxin toxicity and industry estimates for the use of digoxin antibody."	( Digoxin use and digoxin toxicity in the post-DIG trial era. Hauptman, PJ; Hussain, Z; Swindle, J, 2006)	2.02
" There were no adverse maternal events at any of the doses in this study."	( Effectiveness and safety of digoxin to induce fetal demise prior to second-trimester abortion. Bassell, J; Jones, HE; McManama, M; Molaei, M; Weiselberg, T; Westhoff, CL, 2008)	0.64
"0 mg is safe and effective for fetal demise prior to pregnancy termination in the second trimester."	( Effectiveness and safety of digoxin to induce fetal demise prior to second-trimester abortion. Bassell, J; Jones, HE; McManama, M; Molaei, M; Weiselberg, T; Westhoff, CL, 2008)	0.64
"Although digitalis has been used in clinical treatment extensively, the precise mechanism of its toxic actions on cardiovascular system remained unclear, it would be of interest to study the differential proteomic analysis of vascular endothelial cells in response to toxic concentrations of digitalis thus to provide new agents for treatment of digitalis-induced cytotoxicity."	( Comparative proteomics analysis reveals role of heat shock protein 60 in digoxin-induced toxicity in human endothelial cells. Gao, HQ; Liang, Y; Qiu, J; Yu, H; Zhou, RH, 2008)	0.58
" An understanding of structure-activity relationships (SARs) of chemicals can make a significant contribution to the identification of potential toxic effects early in the drug development process and aid in avoiding such problems."	( Developing structure-activity relationships for the prediction of hepatotoxicity. Fisk, L; Greene, N; Naven, RT; Note, RR; Patel, ML; Pelletier, DJ, 2010)	0.36
" An ideal inotropic drug should restore effective tissue perfusion by enhancing myocardial contractility without causing adverse effects."	( Acute heart failure with low cardiac output: can we develop a short-term inotropic agent that does not increase adverse events? Campia, U; Gheorghiade, M; Nodari, S, 2010)	0.36
" Time to recurrence and adverse events were secondary outcomes."	( The study of antiarrhythmic medications in infancy (SAMIS): a multicenter, randomized controlled trial comparing the efficacy and safety of digoxin versus propranolol for prophylaxis of supraventricular tachycardia in infants. Anderson, CC; Bar-Cohen, Y; Batra, AS; Blaufox, AD; Etheridge, SP; Fournier, A; Gibbs, KA; Kanter, RJ; Mackie, AS; McCrindle, BW; Potts, JE; Reed, JH; Ro, PS; Ross, BA; Sanatani, S; Saul, JP; Singh, HR; Stephenson, EA; Tisma-Dupanovic, S; Wong, KK, 2012)	0.58
" This model can be used to identify toxic P-gp substrates with altered safety in dog populations and may reduce dog use in safety studies that are part of the drug approval process."	( P-gp substrate-induced neurotoxicity in an Abcb1a knock-in/Abcb1b knock-out mouse model with a mutated canine ABCB1 targeted insertion. Buckely, LE; Jhingory, MV; Jones, YL; Lancaster, VA; Myers, MJ; Orzechowski, KL; Robl, MG; Swaim, HL; Swain, MD; Tinaza, CA; Yancy, HF, 2013)	0.39
" Most treatment-emergent adverse events were mild, and all resolved by study end."	( Effects of multiple doses of albiglutide on the pharmacokinetics, pharmacodynamics, and safety of digoxin, warfarin, or a low-dose oral contraceptive. Bush, M; Lewis, E; Scott, R; Watanalumlerd, P; Zhi, H, 2012)	0.6
"Because cardenolides specifically inhibit the Na(+)K(+)-ATPase, insects feeding on cardenolide-containing plants need to circumvent this toxic effect."	( Functional evidence for physiological mechanisms to circumvent neurotoxicity of cardenolides in an adapted and a non-adapted hawk-moth species. Dobler, S; Petschenka, G; Pick, C; Wagschal, V, 2013)	0.39
"Dogs with cardiac disease treated with spironolactone, in addition to conventional therapy, are not at higher risk for adverse events (AEs) than those receiving solely conventional therapy."	( Safety of spironolactone in dogs with chronic heart failure because of degenerative valvular disease: a population-based, longitudinal study. Atkins, CE; Baduel, L; Combes, B; Concordet, D; Kaltsatos, V; Lefebvre, HP; Ollivier, E, )	0.13
" Cases were reviewed to determine feasibility, efficacy and adverse events."	( Feasibility, effectiveness and safety of transvaginal digoxin administration prior to dilation and evacuation. Edwards, LJ; Sheeder, JL; Teal, SB; Tocce, K, 2013)	0.64
"Recent data on digoxin prescribing and adverse events are lacking but could help inform the management of digoxin in contemporary heart failure treatment."	( Emergency department visits and hospitalizations for digoxin toxicity: United States, 2005 to 2010. Budnitz, DS; Kegler, SR; Laskar, SR; See, I; Shehab, N, 2014)	1
"We determined nationally representative numbers and rates of emergency department (ED) visits for digoxin toxicity in the United States using 2005 to 2010 reports from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project and the National Ambulatory (and Hospital Ambulatory) Medical Care Surveys."	( Emergency department visits and hospitalizations for digoxin toxicity: United States, 2005 to 2010. Budnitz, DS; Kegler, SR; Laskar, SR; See, I; Shehab, N, 2014)	0.87
"Digoxin-specific antibody fragments (digoxin-Fab) are widely regarded as a safe and effective treatment for the management of acute and chronic digoxin poisoning."	( Digoxin-specific antibody fragments in the treatment of digoxin toxicity. Buckley, NA; Chan, BS, )	3.02
" Adverse events such as exacerbation of heart failure, increased ventricular rate and hypokalaemia are uncommon (< 10%)."	( Digoxin-specific antibody fragments in the treatment of digoxin toxicity. Buckley, NA; Chan, BS, )	1.57
"Digoxin-Fab is safe and indicated in all patients with life-threatening arrhythmias and an elevated digoxin concentration."	( Digoxin-specific antibody fragments in the treatment of digoxin toxicity. Buckley, NA; Chan, BS, )	3.02
"Many adverse drug reactions are caused by the cytochrome P450 (CYP)-dependent activation of drugs into reactive metabolites."	( Development of a cell viability assay to assess drug metabolite structure-toxicity relationships. Jones, LH; Nadanaciva, S; Rana, P; Will, Y, 2016)	0.43
"MATERIAL AND METHOD Enquiries addressed to the Norwegian Poison Information Centre and reports of fatal adverse effects to the Regional Drug Information Centres (RELIS) regarding intake of digitalis were analysed."	( [Drug safety associated with the change of digitalis drug in Norway]. Haga, C; Opdal, MS; Stenberg-Nilsen, H; Tuv, SS; Zahl, PH, 2016)	0.43
"Differences in the management of atrial fibrillation (AF) between men and women were investigated by using Gulf SAFE data in the Middle East."	( Sex differences in management and outcomes of patients with atrial fibrillation in the Middle East: Gulf survey of atrial fibrillation events (Gulf SAFE). Al-Zakwani, I; AlMahmeed, W; AlQudaimi, A; Alsheikh-Ali, AA; Amin, H; Asaad, N; Bhagavathula, AS; Rashed, WA; Shehab, A; Sulaiman, K; Zubaid, M, 2017)	0.46
" The mechanism(s) of toxic action are discussed and treatment modalities are briefly mentioned in relevant cases."	( Comprehensive review of cardiovascular toxicity of drugs and related agents. Applová, L; Costa, VM; Jahodář, L; Karlíčková, J; Mladěnka, A; Mladěnka, P; Patočka, J; Pourová, J; Remiao, F; Štěrba, M; Varner, KJ; Vopršalová, M, 2018)	0.48
" NF-kB promotes inflammatory responses, mediates adverse cardiac remodeling and has a function correlation with calcium."	( High doses of digoxin increase the myocardial nuclear factor-kB and CaV1.2 channels in healthy mice. A possible mechanism of digitalis toxicity. Ashry, IEM; Farghaly, HSM; Hareedy, MS, 2018)	0.84
" However, the rate of hospitalizations for digoxin toxicity and adverse outcomes associated with these hospitalizations have decreased."	( Digoxin Use and Associated Adverse Events Among Older Adults. Angraal, S; Desai, NR; Freeman, JV; Krumholz, HM; Masoudi, FA; Murugiah, K; Nuti, SV; Ranasinghe, I; Shah, ND; Wang, Y, 2019)	2.22
" Furthermore, this mechanism suggests a contribution of the inflammasome to the toxicity and adverse events associated with cardiac glycosides use in humans and that targeted anti-inflammatories could provide an additional adjunct therapeutic countermeasure."	( Inflammasome inhibition blocks cardiac glycoside cell toxicity. Adler, ED; Bushway, PJ; Ettouati, E; LaRock, CN; LaRock, DL; Nizet, V; Richard, M; Sands, JS, 2019)	0.51
"To assess measured C0, to evaluate age influence on digoxin pharmacokinetic parameters and to report adverse events in patients administered digoxin."	( Digoxin therapeutic drug monitoring: age influence and adverse events. Ben Sassi, M; Charfi, R; Daghfous, R; Gaies, E; Jebabli, N; Trabelsi, S, 2020)	2.25
" Adverse events, mainly cardiac and digestive, were reported in 47 patients (36%), among this population 47% were older adults."	( Digoxin therapeutic drug monitoring: age influence and adverse events. Ben Sassi, M; Charfi, R; Daghfous, R; Gaies, E; Jebabli, N; Trabelsi, S, 2020)	2
" This condition may increase risk of adverse events because affected patients are less likely to recognize color vision deficiencies."	( Xanthopsia Due to Digoxin Toxicity as a Cause of Traffic Accidents: A Case Report. Haruna, Y; Kawasaki, T; Kikkawa, Y; Matoba, S; Mizuno, R, 2020)	0.89
" Decision tree (DT) analysis, a machine learning method, has a flowchart-like model where users can easily predict the risk of adverse drug reactions."	( Machine Learning-Based Prediction of Digoxin Toxicity in Heart Failure: A Multicenter Retrospective Study. Arihara, H; Asai, Y; Hashimoto, E; Hayakawa, Y; Hayashi, M; Higuchi, T; Kondo, Y; Muro, H; Omote, S; Suzuki, R; Tanio, E; Tashiro, T; Tsuji, H; Yamada, M; Yamamoto, Y; Yamashita, S, 2023)	1.18
" However, chemotherapy-induced cardiotoxicity is a serious side effect secondary to cardiac damage caused by antineoplastic's direct and indirect toxicity."	( Chemotherapy-induced cardiotoxicity: a new perspective on the role of Digoxin, ATG7 activators, Resveratrol, and herbal drugs. Al-Hussaniy, HA; Al-Samydai, AM; Al-Tameemi, ZS; Al-Zobaidy, MAJ; Alburghaif, AH; Alkhafaje, Z; Alkuraishy, HM; Azam, F; Mostafa-Hedeab, G; Naji, MA, 2023)	1.14
"To determine whether the therapeutic drug levels and adverse events (AEs) associated with renally cleared medications were higher in patients with cancer whose eGFRcys was more than 30% lower than their eGFRcr."	( Medication-Related Adverse Events and Discordancies in Cystatin C-Based vs Serum Creatinine-Based Estimated Glomerular Filtration Rate in Patients With Cancer. Gupta, S; Hanna, PE; Harden, D; Katz-Agranov, N; Leaf, DE; Moreno, D; Ouyang, T; Reynolds, KL; Seethapathy, H; Sise, ME; Strohbehn, IA; Wang, Q, 2023)	0.91
"5 mEq/L), (3) baclofen toxic effect, and (4) supratherapeutic digoxin level (>2."	( Medication-Related Adverse Events and Discordancies in Cystatin C-Based vs Serum Creatinine-Based Estimated Glomerular Filtration Rate in Patients With Cancer. Gupta, S; Hanna, PE; Harden, D; Katz-Agranov, N; Leaf, DE; Moreno, D; Ouyang, T; Reynolds, KL; Seethapathy, H; Sise, ME; Strohbehn, IA; Wang, Q, 2023)	1.15
"07), baclofen toxic effects (5 of 19 [26%] vs 0 of 11; P = ."	( Medication-Related Adverse Events and Discordancies in Cystatin C-Based vs Serum Creatinine-Based Estimated Glomerular Filtration Rate in Patients With Cancer. Gupta, S; Hanna, PE; Harden, D; Katz-Agranov, N; Leaf, DE; Moreno, D; Ouyang, T; Reynolds, KL; Seethapathy, H; Sise, ME; Strohbehn, IA; Wang, Q, 2023)	0.91

Pharmacokinetics

An analysis of pharmacokinetic parameters of digoxin was carried out in six premature infants after the administration of a single total digitalizing dose of 20 microgram/kg. Digoxin half-life (47 +/- 21 h) was inversely related to GA and Wt (r = 0.1). OM coadministered with digoxin or amiodarone did not result in any clinically relevant pharmacokinetics drug-drug interactions.

Excerpt	Reference	Relevance
" It is suggested that more emphasis be given to general pharmacokinetic principles in drug information programs."	( Doses and dosage intervals of drugs--clinical practice and pharmacokinetic principles. Boëthius, G; Sjöqvist, F, 1978)	0.26
" The half-life of elimination in healthy persons varies between 26 and 45 hours."	( Clinical pharmacokinetics of digoxin. Iisalo, E, )	0.42
" None of the identifiable pharmacokinetic variables was significantly influenced by dose, suggesting that digoxin disposition is dose-independent in healthy individuals."	( Dose-independent pharmacokinetics of digoxin in humans. Bodem, G; Greenblatt, DJ; Harmatz, JS; Ochs, HR, 1978)	0.74
" The elimination half-life of digoxin, although variable, did not change appreciably (42 vs."	( Digoxin-quinidine interaction Pharmacokinetic evaluation. Fenster, P; Goldman, S; Graves, P; Hager, WD; Marcus, FI; Mayersohn, M; Perrier, D, 1979)	1.99
" The average serum half-life was prolonged from 37 hours in the control period to 86 hours in the furosemide period."	( Effect of furosemide on serum clearance and renal excretion of digoxin. Fujiki, H; Fukushima, H; Takeda, H; Tsutsumi, E, 1979)	0.5
" The rate of absorption, determined by the time to peak concentration after an oral dose, was more rapid in the younger group."	( Digoxin in the elderly: pharmacokinetic consequences of old age. Cusack, B; Horgan, J; Kelly, J; Lavan, J; Noel, J; O'Malley, K, 1979)	1.7
" From a pharmacokinetic point of view, this treatment scheme does not seem to affect the general behavior of the antibiotic."	( Evaluation of cardiac activity and pharmacokinetic analysis of 3H-adriamycin in patients pretreated with beta-methyldigoxin. Bertuzzi, A; Di Fronzo, G; Ronchetti, L; Ronchi, E; Villani, FP, 1979)	0.47
" The use of pharmacokinetic principles and digoxin radioimmunoassay can improve the overall quality of treatment with this drug and reduce the incidence of adverse reactions."	( Digoxin therapy: a clinical pharmacokinetic approach. Whiting, B, 1978)	1.96
" All animals in each age group exhibited a biexponential elimination of H3-digoxin from the vascular compartment and data are analyzed by use of a two compartment pharmacokinetic model."	( Age dependant factors influencing digoxin pharmacokinetics in the postnatal puppy. Gadgil, S; Mirkin, BL; Singh, S, 1978)	0.77
" An erroneously short half-life of elimination was found in the serum, but in the saliva and urine it was found to be in the range previously reported."	( Estimation of pharmacokinetic parameters of digoxin from serum, saliva and urine. Allonen, H; Iisalo, E; Kangas, L; Lammintausta, R; Salonen, M, 1978)	0.52
"Digoxin dosage regimens for patients on chronic intermittent hemodialysis (CIH) were calculated from pharmacokinetic data of digoxin in these patients between the during hemodialyses."	( Pharmacokinetic aspects of digoxin in patients with terminal renal failure. IV. Clinical implications of own observations with a recent review of literature. Oe, PL; van der Vijgh, WJ, 1978)	2
" Data are lacking relating pharmacokinetic alterations to haemodynamic measurements in patients with cardiac failure."	( Pharmacokinetics in patients with cardiac failure. Benowitz, NL; Meister, W, )	0.13
" The terminal pseudo-steady-state elimination of beta-methyldigoxin with a half-life of 41 hr was reached 27 hr after drug administration and was primarily dependent on the slow release of sequestered or distributed drug drom the tissues into the central compartment."	( Pharmacokinetics of beta-methyldigoxin in healthy humans I: intravenous studies. Garrett, ER; Hinderling, PH; Wester, RD, 1977)	0.79
" The apparent half-life of absorption was 16+/-6 min (SEM)."	( Pharmacokinetics of beta-methyldigoxin in healthy humans II: Oral studies and bioavailability. Garrett, ER; Hinderling, PH; Wester, RC, 1977)	0.54
" The time course of this action correlated with the time course of beta-methyldigoxin and its active metabolite, digoxin, in their deepest pharmacokinetic compartments and not with their plasma levels."	( Pharmacokinetics of beta-methyldigoxin in healthy humans III: Pharmacodynamic correlations. Garrett, ER; Hinderling, PH, 1977)	0.77
" During hemodialysis the mean plasma half-life was 13."	( Pharmacokinetic aspects of digoxin in patients with terminal renal failure. II. On hemodialysis. van der Vijgh, WJ, 1977)	0.55
"A plasma flow rate-limited pharmacokinetic model was developed to describe the distribution of digoxin to the heart, liver, kidneys, skeletal muscle, and GI tract in the rat."	( Physiologically based pharmacokinetic model for digoxin distribution and elimination in the rat. Gibaldi, M; Harrison, LI, 1977)	0.73
"A physiologically based pharmacokinetic model for digoxin disposition developed in the rat was modified to account for the interspecies differences in tissue-to-plasma digoxin concentration ratios and applied to the dog."	( Physiologically based pharmacokinetic model for digoxin disposition in dogs and its preliminary application to humans. Gibaldi, M; Harrison, LI, 1977)	0.77
"Despite the paucity of biopharmaceutic and pharmacokinetic data for many old drugs, these areas of scientific research have demonstrated an immense value in clinical medicine, and can be expected to expand man's knowledge of drug action and the influence of physiological function of drug disposition."	( Importance of biopharmaceutics and pharmacokinetics in clinical medicine. Cabana, BE, 1976)	0.26
"The pharmacokinetic parameters for a two compartment open model were defined for six patients receiving a wide range of Digoxin doses."	( A two compartment open model for digoxin pharmacokinetics in patients receiving a wide range of digoxin doses. Grupp, G; Rabkin, SW, 1975)	0.74
"Current pharmacologic texts recognize no significant pharmacodynamic differences between the various cardiac glycosides."	( Pharmacodynamic distinctions between ouabain, digoxin and digitoxin. Dale, EM; Dalton, RE; Havemann, DF; Holden, P; Kilgore, WM; Runge, TM; Stephens, JC, 1975)	0.51
"Some pharmacokinetic and pharmacodynamic interactions between digoxin and gentamicin were studied in experiments on rabbits, guinea-pigs and cats."	( Some pharmacokinetic and pharmacodynamic interactions between digoxin and gentamicin. Kristeva, E; Prodanova, K; Staneva-Stoytcheva, D, )	0.61
") caused elevation of plasma digoxin levels primarily because the alpha half-life was prolonged (t1/2 alpha)."	( Changes in the plasma levels and basic pharmacokinetic parameters of digoxin used in combination with gentamicin, amiodarone and spironolactone. Krusteva, E, 1992)	0.81
"Routine clinical pharmacokinetic data collected from patients receiving digoxin have been analysed to evaluate the role of patient characteristics for estimating dosing regimens."	( Digoxin population pharmacokinetics from routine clinical data: role of patient characteristics for estimating dosing regimens. Aoyama, T; Higuchi, S; Mine, H; Yukawa, E, 1992)	1.96
"The potential for pharmacokinetic interactions between moxonidine and digoxin at steady-state was investigated in 15 healthy male volunteers."	( Lack of pharmacokinetic interactions between moxonidine and digoxin. Pabst, G; Weber, W; Weimann, HJ, 1992)	0.76
"To study possible pharmacokinetic interactions between two compounds a single-dose or a multiple dose experimental design may be used."	( The importance of prospective planning of pharmacokinetic trials. Considerations of studies on the phenytoin-digoxin-(P-D) and phenytoin-digitoxin-(P-DT) interaction. Rameis, H, 1992)	0.5
" The other pharmacokinetic parameters--the area beneath the curve of serum concentrations, the time before the maximum concentration was attained and the total plasma clearance of digoxin did not differ."	( [Chronopharmacokinetics of digoxin in compensated cardiac patients]. Janků, I; Kopecká, J; Martínková, J; Pidrman, V, 1992)	0.77
" The impact of these postmortem events on the distribution and pharmacokinetic behavior of drugs is described."	( Postmortem changes and pharmacokinetics: review of the literature and case report. Kamps, MA; Lake, KD; Shepherd, MF, 1992)	0.28
" These changes may affect the pharmacokinetic and distribution behavior of certain drugs."	( Postmortem changes and pharmacokinetics: review of the literature and case report. Kamps, MA; Lake, KD; Shepherd, MF, 1992)	0.28
" More studies characterizing the postmortem distribution and pharmacokinetic characteristics of specific drugs are necessary."	( Postmortem changes and pharmacokinetics: review of the literature and case report. Kamps, MA; Lake, KD; Shepherd, MF, 1992)	0.28
" Both steady-state volume of distribution and elimination half-life of acetaminophen were decreased in diabetic rats by 23 and 25%, respectively."	( Long-term diabetes alters the hepatobiliary clearance of acetaminophen, bilirubin and digoxin. Sherman, SE; Watkins, JB, 1992)	0.51
" To separate the effects of transplantation and cyclosporine on digoxin pharmacokinetics, pharmacokinetic studies were subsequently performed in dogs to allow controlled experimental conditions for evaluation of the digoxin-cyclosporine interaction."	( The effects of cardiac transplantation and cyclosporine therapy on digoxin pharmacokinetics. Chung, D; Dorian, P; Klein, J; Koren, G; Ogilvie, R; Robieux, I; Zborowska-Sluis, D, 1992)	0.76
" The elimination half-life of about 22 hours in both groups is much less than that reported in Western data."	( Pharmacokinetics of single dose oral digoxin in patients with uncomplicated type II diabetes mellitus. Adithan, C; Chandrasekar, S; Gitanjali, B; Raveendran, R; Shashindran, CH, 1992)	0.56
"Some pharmacokinetic interactions between digoxin and amiodarone were studied in experiments on rabbits."	( Effects of amiodarone on the pharmacokinetics and toxicity of digoxin in laboratory animals. Kristeva, E; Staneva-Stoytcheva, D, 1992)	0.79
"Some pharmacokinetic and pharmacodynamic interactions between digoxin and gentamicin were studied in experiments on rabbits, guinea-pigs and cats."	( Some pharmacokinetic and pharmacodynamic interactions between digoxin and gentamicin. Kristeva, E; Prodanova, K; Staneva-Stoytcheva, D, 1991)	0.76
"Physiological pharmacokinetic models require the determination of tissue to blood distribution coefficients."	( Potential error in the measurement of tissue to blood distribution coefficients in physiological pharmacokinetic modeling. Residual tissue blood. I. Theoretical considerations. Khor, SP; Mayersohn, M, )	0.13
"3 h; the terminal half-life (t1/2 alpha) was 10."	( The effect of captopril on pharmacokinetics of digoxin in patients with mild congestive heart failure. Ishii, M; Kobayashi, K; Miyakawa, T; Shionoiri, H; Takasaki, I, 1991)	0.54
" Half-life (t1/2) for its net release from LV in buffer was 32."	( Enhanced clearance of specifically bound digoxin from human myocardial and skeletal muscle samples by specific digoxin antibody fragments: subsequent complete digitalis glycoside receptor (Na,K-ATPase) quantification. Kjeldsen, K; Schmidt, TA, 1991)	0.55
" Under iloprost the absorption of digoxin was delayed by about one hour, but the area under the plasma digoxin concentration curve remained unmodified."	( [Treatment with iloprost of critical ischemia of the lower limbs associated with cardiac insufficiency. Study of the interaction with pharmacokinetics of digoxin]. Benchouieb, A; Bouslama, K; Cabane, J; Giral, P; Imbert, JC; Lebas, J; Penin, I; Picard, O; Souvignet, G; Wattiaux, MJ, )	0.61
" Although iloprost slowed the digoxin absorption by approximately one hour, we found no clinically significant difference between the digoxin pharmacokinetic data before and during treatment by iloprost."	( [Treatment with iloprost of critical ischemia of the lower limbs associated with cardiac insufficiency. Study of interaction with the pharmacokinetics of digoxin]. Benchouieb, A; Bouslama, K; Cabane, J; Cheymol, G; Giral, P; Imbert, JC; Penin, I; Picard, O; Souvignet, G; Wattiaux, MJ, )	0.62
"Minimal pharmacokinetic data on digoxin immune Fab are currently available, especially in patients with impaired renal function."	( Clinical and pharmacokinetic profiles of digoxin immune Fab in four patients with renal impairment. Allen, NM; Dunham, GD; Findlay, JW; Sailstad, JM, 1991)	0.83
"Some pharmacokinetic interactions between digoxin and amiodarone were studied in experiments on rabbits."	( Effects of amiodarone on the pharmacokinetics and toxicity of digoxin in laboratory animals. Kristeva, E; Staneva-Stoytcheva, D, 1991)	0.79
" The cardiac glycoside digoxin is subject to a number of pharmacokinetic interactions."	( No effect of probenecid on the renal and biliary clearances of digoxin in man. Angelin, B; Arvidsson, A; Dahlqvist, R; Hedman, A, 1991)	0.83
" On average, Cmax and AUC values for digoxin were approximately 10% higher and tmax tended to be shorter during the administration of omeprazole, while the elimination rate constant was unaffected."	( Minor effect of multiple dose omeprazole on the pharmacokinetics of digoxin after a single oral dose. Andersson, T; Jedema, JN; Jonkman, JH; Oosterhuis, B; Zuiderwijk, PB, 1991)	0.79
" An applied pharmacokinetic approach was used to predict the serum digoxin concentration for each patient."	( Quantifying non-compliance in patients receiving digoxin--a pharmacokinetic approach. Miller, R; Wiseman, IC, 1991)	0.77
" For pharmacokinetic studies, [3H]digoxin and 1 mg/kg unlabeled digoxin were administered as an intravenous bolus dose to animals from each age group."	( The effect of age on digoxin pharmacokinetics in Fischer-344 rats. Evans, RL; Kennedy, RH; Owens, SM; Ruch, S; Seifen, E, 1990)	0.88
" Group-3A dogs had a shortened beta phase half-life (t1/2 (beta] and a decreased distribution volume."	( Influence of induced cholestasis on pharmacokinetics of digoxin and digitoxin in dogs. Akahori, F; Kobayashi, K; Miyashita, H; Miyazawa, Y; Sato, T; Suzuki, T, 1990)	0.53
" The elimination half-life of moricizine is 2 to 6 hours, but its duration of antiarrhythmic action is much longer suggesting active metabolites."	( Clinical pharmacokinetics of moricizine. Barbey, JT; Schwartz, SL; Siddoway, LA; Woosley, RL, 1990)	0.28
"Problems in studying pharmacokinetic interactions with digoxin were evaluated using as a test model the examination of a possible interaction between digoxin and ethmozine in a group of 11 patients with cardiac disease."	( Drug interactions with cardiac glycosides: evaluation of a possible digoxin-ethmozine pharmacokinetic interaction. Antman, EM; Arnold, M; Bosak, M; Friedman, PL; Smith, TW; White, H, 1987)	0.76
" Twenty-five patients underwent oral pharmacokinetic investigation."	( Flecainide acetate for resistant arrhythmias in the young: efficacy and pharmacokinetics. Fredell, P; Garson, A; Gothing, C; McQuinn, RL; Perry, JC; Smith, RT, 1989)	0.28
"Amlodipine, a dihydropyridine calcium antagonist, was synthesized in an attempt to develop a compound with a pharmacokinetic profile characteristic of this class, which would also have an increased oral bioavailability and extended clearance time."	( The pharmacokinetic profile of amlodipine. Abernethy, DR, 1989)	0.28
" Repeated blood sampling over 19 days revealed an apparent elimination half-life (t1/2) of 134."	( Pharmacokinetics and efficacy of digoxin specific Fab fragments in a child following massive digoxin overdose. Clayton, BD; Hewett, DD; Kearns, GL; Moss, MM, 1989)	0.56
" The renal clearance and half-life of digoxin were not significantly altered by propafenone."	( Effects of coadministration of propafenone on the pharmacokinetics of digoxin in healthy volunteer subjects. Erstad, BL; Furman, C; Hoyer, GL; Kirsten, EB; Marcus, FI; Nolan, PE, 1989)	0.78
"Digoxin-induced bradycardia in dogs was used to evaluate several pharmacodynamic models."	( Pharmacodynamic modeling of digoxin-induced bradycardia. Allison, TB; Barr, WH; Vetticaden, SJ, 1989)	2.01
" Although total clearance, elimination half-life and steady-state volume of distribution were not altered, biliary clearance of acetaminophen was decreased by 39 to 50%."	( Exposure of rats to inhalational anesthetics alters the hepatobiliary clearance of cholephilic xenobiotics. Watkins, JB, 1989)	0.28
"To evaluate the effects of compensated heart failure (HF) on digoxin pharmacokinetic properties in cats, 6 cats with dilated cardiomyopathy were compared with 6 clinically normal (control) cats."	( Effects of compensated heart failure on digoxin pharmacokinetics in cats. Atkins, CE; Keene, BW; Rush, JE; Snyder, PS, 1989)	0.79
"In a pharmacokinetic drug interaction study, the purpose is to determine whether the coadministration of a drug A with a second drug B alters the absorption/distribution/metabolism/elimination profile of either drug."	( The statistical evaluation of a three-period two-treatment crossover pharmacokinetic drug interaction study. Bolognese, JA; Ciminera, JL; Gregg, MH, 1987)	0.27
" The mean half-life of digoxin in the healthy volunteers (37."	( Clinical pharmacokinetics of digoxin in Nigerians. Iyun, AO; Lukanbi, FA, 1988)	0.88
"The clinical pharmacology and pharmacodynamic data from several clinical trials are summarized."	( Clinical pharmacology, pharmacodynamics and interactions with esmolol. Bies, CM; Lowenthal, DT; Porter, RS; Saris, SD; Slegowski, MB; Staudacher, A, 1985)	0.27
" Furthermore, ibopamine-quinidine pharmacokinetic interaction and the effects of food on plasma kinetics were evaluated in NS."	( Clinical pharmacokinetics of ibopamine on different diseases and conditions. Lodola, E; Ventresca, GP, 1988)	0.27
"1) increase in peripheral volume of distribution contributed to prolonged elimination half-life (23."	( The comparative effects of verapamil and a new dihydropyridine calcium channel blocker on digoxin pharmacokinetics. Hoch, K; Johnson, BF; Johnson, J; Marwaha, R; Wilson, J, 1987)	0.49
"Numerous pharmacological agents have been shown to produce clinically significant pharmacokinetic interactions with digoxin."	( Pharmacokinetic interactions with digoxin. Johnson, BF; Rodin, SM, 1988)	0.76
" This is the first demonstration in man of a pharmacokinetic drug interaction at the level of biliary excretion."	( Quinidine reduces biliary clearance of digoxin in man. Angelin, B; Arvidsson, A; Dahlqvist, R; Hedman, A; Schenck-Gustafsson, K, 1987)	0.54
" The dual purpose of the present study was to evaluate the influence of orally administered nicardipine on plasma digoxin concentrations over 24 hours and to measure possible variations in the pharmacodynamic effects of digoxin in 9 patients with chronic congestive heart failure."	( [Pharmacokinetics and pharmacodynamic effects of digoxin in dilated cardiomyopathies. Influence of nicardipine]. Commeau, P; Debruyne, D; Dorey, H; Gérard, JL; Grollier, G; Huret, B; Lamy, E; Moore, N; Potier, JC; Scanu, P, 1987)	0.74
" Studies on the relationship between pharmacodynamics and pharmacokinetics show that the optimum use of urapidil in clinical practice depends on an understanding of the pharmacokinetic properties of the drug."	( Clinical pharmacokinetics of urapidil. Haerlin, R; Kirsten, R; Nelson, K; Steinijans, VW; Zech, K, 1988)	0.27
" These observations are in good agreement with the findings obtained in a pharmacokinetic study that RIA gave significantly higher levels than FPIA, only in the early stage after MD administration, resulting in a smaller total volume of distribution and a larger beta value in the elimination phase, as compared with FPIA."	( Variances in pharmacokinetic parameters due to assay methods for beta-methyldigoxin. Goto, M; Johno, I; Kitazawa, S; Suzuki, A; Terashima, T, 1987)	0.5
"The purpose of this study was to determine if serum digoxin concentration data using three different automated immunoassay methods would produce similar pharmacokinetic values in normal volunteer subjects."	( Lack of apparent effect of assay methodology on the pharmacokinetics of digoxin. Blum, RA; Crass, RE; DeVito, JM; Gadsden, RH; Leman, RB; Pleasants, RA, 1987)	0.76
" The absorption characteristics Cmax and Tmax were calculated both for felodipine and digoxin on the different felodipine doses."	( Pharmacokinetics of felodipine and effect on digoxin plasma levels in patients with heart failure. Billing, E; Lundman, T; Moberg, L; Olsson, G; Rehnqvist, N, 1987)	0.76
"The influence of bepridil on steady-state serum digoxin concentrations (SDCs) and the pharmacodynamic actions of both drugs were tested in 48 healthy subjects in a randomized, double-blind study."	( Digoxin and bepridil: pharmacokinetic and pharmacodynamic interactions. Belz, GG; Matthews, JH; Wistuba, S, 1986)	1.97
"The appropriateness of requests by physicians for serum digoxin measurements (SDMs) and the appropriateness of responses by physicians to a reported SDM were evaluated with and without the contribution of a pharmacy-based clinical pharmacokinetic service (CPS)."	( An evaluation of a clinical pharmacokinetic service for serum digoxin levels. Blain, L; Michalko, KJ, 1987)	0.76
"005), in area under the serum-digoxin concentration curve (4 h: 520."	( [Effect of propafenone on the pharmacokinetics of digoxin administered orally: a study in healthy volunteers]. Cardaioli, P; Compostella, L; Cucchini, F; De Domenico, R; Libardoni, M; Papalia, D; Pulido, E; Zeppellini, R, 1986)	0.81
" Digoxin pharmacokinetic patterns are analysed with reference to baseline myocardial contractility."	( [Pharmacokinetics of digoxin in middle-aged and elderly patients in the subacute period of myocardial infarction]. Glezer, MG; Grigor'eva, EA; Iakovlev, SV; Kholodov, LE; Mikhaĭlov, AA, 1986)	1.5
" The method deals with individual linear compartmental mammillary pharmacokinetic models and requires estimated values of model parameters."	( Steady-state dosage regimen calculations in linear pharmacokinetics. Bruno, R; Cano, JP; Iliadis, A, 1986)	0.27
" None of these pharmacokinetic parameters of digoxin were significantly different before or during diltiazem administration."	( Digoxin-diltiazem interaction: a pharmacokinetic evaluation. Bliss, M; Goldman, S; Jones, WN; Kern, KB; Mayersohn, M; Rindone, JP, 1986)	1.97
"The usefulness of pharmacokinetic predictions of serum digoxin concentrations was evaluated in a group of 19 elderly residents of a nursing home."	( Pharmacokinetic prediction of serum digoxin concentration in the elderly. Mooradian, AD; Wynn, EM, 1987)	0.8
"Bepridil hydrochloride differs from the other calcium antagonists in structure as well as in several clinical pharmacokinetic characteristics."	( Pharmacokinetics and metabolism of bepridil. Benet, LZ, 1985)	0.27
"The potential for a pharmacokinetic interaction between the investigational antiarrhythmic drug ethmozine (moricizine HCl, the generic name that is infrequently used in existing literature) and digoxin was evaluated in nine healthy male adults."	( Assessment of the potential pharmacokinetic interaction between digoxin and ethmozine. MacFarland, RT; Marcus, FI; Moeller, VR; Pieniaszek, HJ; Whitney, CC, 1985)	0.7
" Based on the available data it seems that one may postulate the following conclusions: (1) that the distribution factors as well as changes in drug elimination capacities seem to play a role, perhaps with differing relative importance, during each of the maturational periods; (2) that the physicochemical properties of a drug and its dosage, as well as changes in the volume of distribution in children, in the course of certain disease states may have a significant effect on kinetics of drug disposition in the body; (3) that systemic clearance, a model independent parameter, rather than elimination half-life, a hybrid pharmacokinetic parameter, more accurately reflects elimination of some drugs from the body; (4) that each drug and every clinical situation may require the evaluation of the direct effect on pharmacokinetic processes, since general principles may not always apply; (5) that drug disposition studies should also be performed, if possible, on patients under actual clinical situations and receiving the usual therapeutic regime, and (6) that the half-life of colistin is independent of postnatal age which should serve as a warning not to generalize about drug excretion in the young infant."	( Clinical pharmacokinetics of changes in drug elimination in children. Prandota, J, 1985)	0.27
" Mean values for peak concentration, area under the serum concentration time curve (AUC), total serum clearance and the half-life of elimination of nifedipine did not differ before and concomitantly with digoxin administration."	( Pharmacokinetic studies of nifedipine and digoxin co-administration. Granit, L; Koren, G; Levy, M; Zylber-Katz, E, 1986)	0.72
" This study was designed to evaluate the pharmacokinetic basis of this interaction in 10 normal subjects."	( Pharmacokinetic evaluation of the digoxin-amiodarone interaction. Fenster, PE; Hanson, CD; White, NW, 1985)	0.55
"This study was done to determine the effects of a pharmacokinetic service (PKS) on digoxin concentration monitoring and patient outcomes, including length of stay and toxicity measures."	( Evaluation of a digoxin pharmacokinetic monitoring service in a community hospital. Christensen, DB; deBlaquiere, PA; Horn, JR, 1985)	0.84
" Coadministration of quinidine sulphate induces a prolongation of digoxin elimination half-life (means +/- SD) from 33."	( Quinidine-digoxin interaction: are the pharmacokinetics of both drugs altered? Rameis, H, 1985)	0.91
" Pharmacokinetic parameters were estimated for the liposoluble (dichloromethane soluble) material in the water phase obtained by centrifugation of the emulsion, for the liposoluble material and unchanged gitoxin in the total emulsion."	( A further study of the pharmacokinetics of gitoxin in rabbit isolated liver: clearance of 3H-gitoxin. Lesne, M; Pellegrin, PL, )	0.13
"The pharmacokinetic interaction between digoxin (1) and amiodarone (2) has drawn increasing attention during recent years, but the tissue correlates of such an interaction are not known."	( Tissue-serum correlates of digoxin-amiodarone pharmacokinetic interaction in rats: evidence for selective tissue accumulation and reduced tissue binding. Al-Sarraf, L; Kannan, R; Singh, BN; Venkatesh, N, 1985)	0.83
" The pharmacodynamic response was a dose-related fall in the systemic arterial pressure, both supine and standing; dose-response effects were most evident in the upright posture."	( The pharmacokinetic, pharmacodynamic and haemodynamic effects of acute and chronic alpha-adrenoceptor blockade in chronic heart failure. Silke, B; Taylor, SH, 1981)	0.26
"The pharmacokinetic properties and dosage guidelines for digoxin in pediatric patients with congestive heart failure are reviewed."	( Digoxin pharmacokinetics and dosage requirements in pediatric patients. Bendayan, R; McKenzie, MW, )	1.82
" Unlike other calcium antagonists, detailed pharmacokinetic data are available for verapamil."	( Clinical pharmacokinetics of verapamil. Blouin, RA; Hamann, SR; McAllister, RG, )	0.13
" As yet, its pharmacokinetic behaviour has not been satisfactorily characterised."	( Clinical pharmacokinetics of amiodarone. Kates, RE; Latini, R; Tognoni, G, )	0.13
"The theory of Bayesian analysis and its application to therapeutic and pharmacokinetic decision making are discussed."	( Bayesian approaches in pharmacokinetic decision making. Barr, JT; Schumacher, GE, )	0.13
" Treatments were compared by evaluating the following model-independent pharmacokinetic parameters: maximum serum concentration (Cmax); time of maximum serum concentration (tmax); area under the serum concentration-time curve for 0-12 h (AUC0-12); cumulative urinary excretion for 0-48 h (CUE48)."	( Bioavailability of digoxin capsules and tablets: effect of coadministered fluid volume. Bustrack, JA; Christenson, RH; Foster, JR; Hammond, JE; Hull, JH; Katz, JD, 1984)	0.6
"001) and increased the plasma half-life of the drug from 33."	( Influence of verapamil on the inotropism and pharmacokinetics of digoxin. Christiansen, BD; Klitgaard, NA; Nielsen-Kudsk, F; Pedersen, KE; Thayssen, P, 1983)	0.5
" Following an open two-compartment model a mean elimination half-life of 60."	( On the pharmacokinetics of pengitoxin and its cardioactive derivative 16-acetyl-gitoxin. Alken, RG; Becker, U; Haustein, KO; Lach, HJ; Rietbrock, N, 1983)	0.27
" No pharmacodynamic interaction as assessed by changes in the systolic time intervals QA2 and LVET was found."	( Pharmacokinetics of digoxin alone and in the presence of indomethacin therapy. Finch, MB; Johnston, GD; Kelly, JG; McDevitt, DG, 1984)	0.59
" The pharmacokinetic data were interpreted in terms of a two-compartmental model."	( [Effect of age on the pharmacokinetic parameters of digoxin]. Belyĭ, AA; Bezverkhaia, IS; Korkushko, OV; Orlov, PA, )	0.38
"Simultaneous oral administration of digoxin and three benzamides (Metoclopramide, Alizapride, Bromopride) to the rat, modify digoxin's pharmacokinetic parameters: peak plasma concentration, elimination phase half life and bioavailability (Bromopride, Alizapride in function with dose-level)."	( Pharmacokinetic study of digoxin-benzamide interaction in the rat. Jacquot, C; Metivier, B; Renault, H; Servin, A, 1984)	0.85
" Other pharmacokinetic parameters (alpha, beta, V1, V2."	( Hepatic clearance of gitoxin: pharmacokinetic study on rabbit isolated liver. Influence of protein binding and comparison with digoxin. Lesne, M; Pellegrin, P, 1983)	0.47
" Plasma half-life increased from 51."	( Changes in steady state digoxin pharmacokinetics during quinidine therapy in cardiac patients: influence of plasma quinidine concentration. Christiansen, BD; Klitgaard, NA; Nielsen-Kudsk, F; Pedersen, KE, 1983)	0.57
" Paracetamol, the only metabolised drug which is conjugated for which pharmacokinetic parameters have been accurately determined in obesity, undergoes increased clearance in obese subjects."	( Pharmacokinetics of drugs in obesity. Abernethy, DR; Greenblatt, DJ, )	0.13
"A package of integrated programs for calculating pharmacokinetic variables and drug-dosing regimens using a hand-held programmable calculator is described."	( Integrated calculator programs for pharmacokinetic calculations. Bauer, LA; Koup, JR; Robb, RA, 1982)	0.26
"An analysis of pharmacokinetic parameters of digoxin was carried out in six premature infants after the administration of a single total digitalizing dose of 20 microgram/kg."	( Digoxin pharmacokinetics in premature infants. Benawra, R; Chiou, WL; Hastreiter, AR; Lam, G; Mangurten, H; Simonton, RL; van der Horst, RL, 1982)	1.97
" No significant difference between ewes and newborns was shown for drug distribution half-life (0."	( The pharmacokinetics of digoxin in newborn and adult sheep. Berman, W; Musselman, J; Shortencarrier, R, 1982)	0.57
" There were no significant differences in digoxin half-life of elimination between the two states."	( Digoxin pharmacokinetics in congestive heart failure. Adir, J; Applefeld, MM; Crouthamel, WG; Roffman, DS, )	1.84
" Pharmacokinetic parameters were determined by weighted iterative nonlinear least squares regression analysis."	( Digoxin disposition in obesity: clinical pharmacokinetic investigation. Abernethy, DR; Greenblatt, DJ; Smith, TW, 1981)	1.71
" The data were fitted to a two compartment open pharmacokinetic model."	( Pharmacokinetics of digoxin in the turkey and comparison with other species. Einzig, S; Noren, GR; Park, E; Staley, NA, 1981)	0.59
"6 ng/ml) at approximately 1 hour after dosing and had a half-life of 28."	( Pharmacokinetics of a single, orally administered dose of digoxin in horses. Belmonte, AA; McCullers, RM; Pedersoli, WM; Ravis, WR, 1981)	0.51
" The pharmacokinetic changes in elderly are therefore multiple, and can hardly be predicted in the individual case."	( [Changes in pharmacokinetics in the aged and their practical consequences]. Höffler, D, )	0.13
"/kg), prolonged its elimination half-life (47."	( Impairment of digoxin clearance by coadministration of quinidine. Bodem, G; Greenblatt, DJ; Ochs, HR, 1981)	0.62
" Our finding of slower renal digoxin clearance helps to explain the higher serum levels and longer half-life of this drug in premature neonates."	( Renal clearance of digoxin in premature neonates. Collins-Nakai, RL; Cote, J; Ng, PK; Schiff, D, 1981)	0.88
"The article deals with the shortcomings of pharmacokinetic models in predicting tissue-concentrations of drugs."	( [Pharmacokinetic problems in surgery]. Fabian, W; Fellmann, E; Hropot, M; Muschaweck, R; Sörgel, F, 1980)	0.26
" For this and other reasons, at the Hospital Pharmacological Service a clinical pharmacokinetic laboratory was set up about two years ago."	( Clinical pharmacokinetics: the pharmacological monitoring of plasmatic levels in therapy. Bonora, MR; Guaglio, R; Rondanelli, R; Terzoni, PA, 1980)	0.26
" In a subsequent study, we demonstrated that ischemic stroke caused a significant prolongation in the elimination half-life of digoxin and an increase in the volume of distribution."	( The effects of acute focal cerebral ischemia on digoxin toxicity and pharmacokinetics. Das, SK; Jallad, NS; Keener, DB; Wagner, JG; Weidler, DJ, 1980)	0.72
" No significant differences were found in the following experiments with digoxin and ouabain in control and protein-deficient animals: inotropic effects of ouabain on isolated papillary muscles and left atria; uptake of [3H]ouabain by isolated papillary muscles; ventricular fibrillatory doses of digoxin and ouabain in anesthetized animals and the concentrations of digoxin in plasma and papillary muscles at the onset of ventricular fibrillation in these animals; plasma half-life of digoxin in unanesthetized guinea pigs."	( Myocardial effects and pharmacokinetics of digoxin and ouabain in protein-deficient guinea pigs. Varma, DR, 1980)	0.76
" A dosing schedule based on the creatinine clearance, body weight and volume of distribution has been developed from pharmacokinetic data taken from the literature."	( Digoxin dosage in renal insufficiency: impracticality of basing it on the creatinine clearance, body weight and volume of distribution. Ingerowski, R; Keller, F; Molzahn, M, 1980)	1.7
" Data collected in this series of experiments and data from the literature were applied to standard pharmacokinetic equations to formulate loading and maintenance doses of digoxin for the IV injection, the elixir, and the tablet."	( Pharmacokinetics, bioavailability, and dosage regimens of digoxin in dogs. Button, C; Gross, DR; Johnston, JT; Yakatan, GJ, 1980)	0.7
" Standard pharmacokinetic equations and mean pharmacokinetic variables were used to derive parenteral and oral (loading and maintenance) doses for digoxin in horses."	( Digoxin pharmacokinetics, bioavailability, efficacy, and dosage regimens in the horse. Button, C; Gross, DR; Johnston, JT; Yakatan, GJ, 1980)	1.9
" The results of this study indicate that, in healthy young men, co-administration of tenidap with digoxin does not have any apparent clinically significant effects on the pharmacokinetic profile of digoxin, and the treatment is well tolerated."	( Effect of tenidap sodium on digoxin pharmacokinetics in healthy young men. Coates, PE; Dewland, PM; Grimwood, VC; Rapeport, WG, 1995)	0.8
" Pharmacokinetic studies have not been performed in healthy volunteers, but there are limited kinetic data from patients who have received therapy for the treatment of digoxin toxicity."	( Pharmacokinetic aspects of digoxin-specific Fab therapy in the management of digitalis toxicity. Robert, S; Ujhelyi, MR, 1995)	0.78
"To evaluate an animal model of multiple-dose activated charcoal (MDAC) therapy and correlate the pharmacokinetic properties of four drugs with the efficacy of MDAC."	( Correlation of drug pharmacokinetics and effectiveness of multiple-dose activated charcoal therapy. Chyka, PA; Holley, JE; Mandrell, TD; Sugathan, P, 1995)	0.29
" Pharmacokinetic assays were performed in all animals after 2 months of the experiment."	( Effect of experimental hyperlipidemia on the pharmacokinetics of digoxin. Drozdzik, M; Gawrońska-Szklarz, B; Wójcicki, J; Zakrzewski, J, 1994)	0.53
" In contrast, there were no observed differences in pharmacokinetic parameters, serum elimination, or biliary excretion for the clinically important cardiac glycoside digoxin (dose of 100 nmol/kg)."	( Chronic voluntary exercise may alter hepatobiliary clearance of endogenous and exogenous chemicals in rats. Crawford, ST; Sanders, RA; Watkins, JB, )	0.33
" The following pharmacokinetic parameters were determined using noncompartmental techniques: area under the curve for 24 hours (AUC24); time to maximum concentration after digoxin (tmax); maximum concentration after digoxin dosing (Cmax); concentration at 24 hours after fluvastatin or placebo (Cmin); total amount excreted in the urine over 24 hours (U24); and urinary clearance (Clren)."	( Pharmacokinetic effects of fluvastatin in patients chronically receiving digoxin. Dimenna, G; Garnett, WR; Venitz, J; Wilkens, RC, 1994)	0.71
"The pharmacokinetic and pharmacodynamic effects of co-administration of flosequinan (BTS 49465, CAS 76568-02-0) and digoxin (CAS 20830-75-5) were investigated in 12 healthy volunteers."	( Effects of concurrent administration of flosequinan and digoxin on the pharmacokinetics of each drug. Hind, ID; Rau, R; White, SA; Wynne, RD, 1994)	0.74
"In three groups (each n = 12) of unselected hospitalized patients treated either with digoxin, theophylline, or gentamicin routinely performed TDM measurement of trough steady-state plasma levels (+ peak levels in case of gentamicin) was combined with a pharmacokinetic study at steady state (multiple blood sampling during one dosing interval)."	( Generation of pharmacokinetic data during routine therapeutic drug monitoring: Bayesian approach vs. pharmacokinetic studies. Bühl, K; Drewelow, B; el Desoky, E; Engel, G; Harings-Kaim, A; Klotz, U; Meinshausen, J, 1993)	0.51
" Systemic exposure is limited because of extensive sequestration by the liver and/or first-pass metabolism, a plasma half-life of approximately 30 min, no circulating active metabolites, and no accumulation of drug during chronic dosing."	( Pharmacokinetics of fluvastatin and specific drug interactions. Hwang, DS; Jokubaitis, LA; Robinson, WT; Smith, HT; Troendle, AJ, 1993)	0.29
" RIA was applied to the pharmacokinetic study of sheep digoxin-specific Fab fragments in one patient acutely intoxicated by digitoxin and treated with Digidot."	( Development of a sensitive radioimmunoassay for Fab fragments: application to Fab pharmacokinetics in humans. Cano, NJ; Sabouraud, AE; Scherrmann, JM; Thanh-Barthet, CV; Urtizberea, M, 1993)	0.53
"36 ng/mL), time to peak concentration (3 versus 4 hours), and apparent oral clearance of digoxin (237."	( Digoxin pharmacokinetics and perindopril in heart failure patients. Desche, P; Dews, IM; Resplandy, G; Robinson, J; Stephens, JD; Vandenburg, MJ, 1993)	1.95
"2 mg) to 24 patients with various degrees of renal function, to investigate its pharmacokinetic characteristics related to renal function."	( Pharmacokinetics of beta-methyldigoxin in subjects with normal and impaired renal function. Imagawa, M; Nakano, S; Nakashima, H; Tateishi, T; Tsutsumi, K, 1993)	0.57
" In the present study we evaluated the pharmacokinetic behaviour of digoxin and the factors responsible for intoxication by this drug in monitored patients exhibiting clinical signs of overdosing with serum levels > 2 ng/ml."	( Digoxin pharmacokinetics in patients with high serum digoxin concentrations. Calvo, MV; Domínguez-Gil, A; Lanao, JM; Martín, P; Martín-Suárez, A, 1993)	1.96
" The 90% confidence intervals for the ratio of geometric least-squares means (for Cmax, AUC0-48, AUC0-t, and AUC) and for the difference of arithmetic least-squares means (for tmax and lambda z) indicate that the pharmacokinetics of digoxin was not altered by treatment with orlistat."	( The influence of reduced dietary fat absorption induced by orlistat on the pharmacokinetics of digoxin in healthy volunteers. Arora, S; Freundlich, NL; Koss-Twardy, SG; Melia, AT; Min, BH; Passe, SM; Smith, BL; Zhi, J, 1995)	0.69
" The elimination half-life in patients with normal renal function is approximately 40-60 h, but is significantly increased in subjects with severe renal impairment."	( Human pharmacokinetics of tiludronate. Necciari, J; Sansom, LN; Thiercelin, JF, 1995)	0.29
"The effects of coadministration of zileuton on the pharmacokinetic profile of digoxin were investigated in a double-blind placebo-controlled crossover study in 12 healthy male volunteers."	( Assessment of the pharmacokinetic interaction between zileuton and digoxin in humans. Awni, WM; Cavanaugh, JH; Dubé, LM; Granneman, GR; Hussein, Z, 1995)	0.76
"Digoxin-specific Fab are recognized to be effective in the treatment of acute cardiac glycoside poisoning but no pharmacokinetic studies have been performed in human volunteers."	( Interspecies scaling of clearance and volume of distribution for digoxin-specific Fab. Bazin-Redureau, MI; Debray, M; Grene-Lerouge, NA; Scherrmann, JM, 1996)	1.97
" Blood and urine samples were collected for pharmacokinetic analyses."	( Effect of diprafenone on the pharmacokinetics of digoxin. Alken, RG; Koytchev, R; Mayer, O, 1996)	0.55
"A previously validated physiologically based pharmacokinetic model was used to examine whether epoprostenol-induced increases in gastrointestinal blood flow (Qg) could alter digoxin systemic bioavailability to a clinically significant extent in severe congestive heart failure (CHF) patients."	( Physiologic pharmacokinetic modeling of gastrointestinal blood flow as a rate-limiting step in the oral absorption of digoxin: implications for patients with congestive heart failure receiving epoprostenol. Brouwer, KL; Carlton, LD; Pollack, GM, 1996)	0.7
"The effect of nefazodone on pharmacokinetic and pharmacodynamic parameters of digoxin were evaluated in an open, randomized, multiple-dose, three-way crossover study of 18 healthy male volunteers."	( Assessment of pharmacokinetic and pharmacodynamic drug interactions between nefazodone and digoxin in healthy male volunteers. Barbhaiya, RH; Dockens, RC; Greene, DS, 1996)	0.74
" This communication highlights the possible pharmacokinetic basis of the reported digoxin-nifedipine interaction."	( Pharmacokinetic basis of nifedipine-digoxin interaction: a commentary. Kokwaro, GO, 1995)	0.79
" Analysis of the pharmacokinetics of digoxin was accomplished with a simple steady-state pharmacokinetic model."	( Population-based investigation of relative clearance of digoxin in Japanese patients by multiple trough screen analysis: an update. Aoyama, T; Higuchi, S; Honda, T; Ohdo, S; Yukawa, E, 1997)	0.82
"To investigate the potential pharmacokinetic and pharmacodynamic interaction between imidapril and digoxin."	( Pharmacokinetic and pharmacodynamic interaction trial after repeated oral doses of imidapril and digoxin in healthy volunteers. Harder, S; Thürmann, PA, 1997)	0.73
" Cmax was 19."	( Pharmacokinetic and pharmacodynamic interaction trial after repeated oral doses of imidapril and digoxin in healthy volunteers. Harder, S; Thürmann, PA, 1997)	0.51
" Two-compartment pharmacokinetic parameters (zero-time intercept of the concentration-time curve of the initial distribution phase [A], zero-time intercept of the concentration-time curve of the terminal elimination phase [B], initial distribution phase constant [alpha], terminal elimination rate constant [beta], volume of distribution in the central compartment [Vc] and at steady state [Vss], total body clearance [Cl], mean residence time [MRT], area under the concentration-time curve [AUC]) were determined using a nonlinear least squares regression program."	( Is the volume of distribution of digoxin reduced in patients with renal dysfunction? Determining digoxin pharmacokinetics by fluorescence polarization immunoassay. Charland, SL; Cheng, JW; Goldfarb, S; Kobrin, S; Shaw, LM; Spinler, SA; Stanek, EJ, )	0.41
" tmax was similar for both regimens."	( Lack of effect of eprosartan on the single dose pharmacokinetics of orally administered digoxin in healthy male volunteers. Boike, SC; Citerone, D; Ilson, B; Jorkasky, DK; Martin, DE; Tenero, D; Tompson, D, 1997)	0.52
"Based on AUC and Cmax data, it can be concluded that eprosartan has no effect on the pharmacokinetics of a single oral dose of digoxin."	( Lack of effect of eprosartan on the single dose pharmacokinetics of orally administered digoxin in healthy male volunteers. Boike, SC; Citerone, D; Ilson, B; Jorkasky, DK; Martin, DE; Tenero, D; Tompson, D, 1997)	0.72
" Although the time to maximum peak concentration with terbinafine was slightly reduced, the maximum concentration and area under the serum drug concentration-time curve from time zero to 120 hours were not significantly different with terbinafine than with placebo."	( Effects of terbinafine on the pharmacokinetics of digoxin in healthy volunteers. Francheteau, P; Guerret, M; Tarral, A, )	0.38
"The aim of this series of studies was to determine the potential for pharmacokinetic interaction between candesartan (administered orally as the prodrug candesartan cilexetil) and hydrochlorothiazide (HCTZ), nifedipine, glibenclamide, warfarin, digoxin or the components of an oral contraceptive formulation."	( Pharmacokinetic drug interaction studies with candesartan cilexetil. Högemann, A; Jonkman, JH; Lins, R; Sennewald, R; van Heiningen, PN; van Lier, JJ, 1997)	0.48
" Biomedical and anatomo-pathological tests and pharmacokinetic assays were performed before the operation and on the 6th day after surgery."	( Pharmacokinetics of intragastrically administered digoxin in rabbits with experimental bile duct obstruction. Drozdzik, M; Gawronska-Szklarz, B; Musial, HD; Rózewicka, L; Skowron, J; Sulikowski, T; Wójcicki, J; Wójcicki, M; Zakrzewski, J; Zielinski, S, 1997)	0.55
" The increases in digoxin Cmax and T(1/2) by itraconazole were not statistically significant."	( Itraconazole decreases renal clearance of digoxin. Jalava, KM; Neuvonen, PJ; Partanen, J, 1997)	0.9
" Mean values for maximum concentration (Cmax), time to Cmax (tmax), and area under the concentration-time curve from 0 to 24 hours (AUC0-24) of digoxin on day 10 were similar to those on day 20."	( Effect of troglitazone on steady-state pharmacokinetics of digoxin. Knowlton, PW; Koup, JR; Loi, CM; Randinitis, EJ; Sedman, AJ; Stern, R; Vassos, AB, 1998)	0.74
" No change in AUC and tmax was recorded."	( Lack of effect of mizolastine on the safety and pharmacokinetics of digoxin administered orally in repeated doses to healthy volunteers. Chaufour, S; Cimarosti, I; Delhotal-Landes, B; Denolle, T; Deschamps, C; Dubruc, C; Le Coz, F; Rosenzweig, P; Ulliac, N, 1998)	0.54
" While pharmacokinetic changes in the elderly are usually well characterised, pharmacodynamic changes are understood only in the most preliminary way."	( Pharmacokinetic and pharmacodynamic changes in the elderly. Clinical implications. Derendorf, H; Hämmerlein, A; Lowenthal, DT, 1998)	0.3
"To assess the possibility of any clinically relevant pharmacokinetic interactions between tiagabine, a novel antiepileptic drug, and digoxin."	( Tiagabine, a novel antiepileptic agent: lack of pharmacokinetic interaction with digoxin. Jansen, JA; Jonkman, JH; Pedersen, PC; Snel, S; van Heiningen, PN, 1998)	0.73
"Potential pharmacokinetic interactions between tiagabine and digoxin were investigated in an open-label, two-period cross-over study in healthy male volunteers."	( Tiagabine, a novel antiepileptic agent: lack of pharmacokinetic interaction with digoxin. Jansen, JA; Jonkman, JH; Pedersen, PC; Snel, S; van Heiningen, PN, 1998)	0.77
"No statistically significant differences between treatment groups were observed for any of the derived digoxin pharmacokinetic parameters."	( Tiagabine, a novel antiepileptic agent: lack of pharmacokinetic interaction with digoxin. Jansen, JA; Jonkman, JH; Pedersen, PC; Snel, S; van Heiningen, PN, 1998)	0.74
"At the doses administered, there is no evidence of a pharmacokinetic interaction between digoxin and tiagabine in healthy male volunteers."	( Tiagabine, a novel antiepileptic agent: lack of pharmacokinetic interaction with digoxin. Jansen, JA; Jonkman, JH; Pedersen, PC; Snel, S; van Heiningen, PN, 1998)	0.75
"25 mg) produced no changes in the pharmacokinetic profile of either drug."	( Concurrent administration of donepezil HCl and digoxin: assessment of pharmacokinetic changes. Friedhoff, LT; Perdomo, CA; Tiseo, PJ, 1998)	0.56
" Pharmacokinetic consultation services have been implemented in many teaching hospitals and tertiary care facilities in the past."	( A regional pharmacokinetic consultation service. Bédard, M; McLean, W, 1994)	0.29
"Sparfloxacin, a broad-spectrum, oral fluoroquinolone antimicrobial agent, has a long elimination half-life that permits once-daily administration."	( Pharmacokinetic interaction of sparfloxacin and digoxin. Conway, S; Dorr, MB; Hunt, TL; Johnson, RD; Talbot, GH, 1999)	0.56
" Based on these results, the pharmacokinetic interaction between DGX and ITZ may be due not only to a reduction in the renal clearance but also to a reduction in the metabolic clearance of DGX by ITZ."	( Effect of itraconazole on the pharmacokinetics of digoxin in guinea pigs. Hibino, J; Iga, T; Kotaki, H; Nishihara, K; Sawada, Y, 1999)	0.56
"A pharmacy-conducted digoxin pharmacokinetic consultation service was implemented to determine the influence of the service on patient serum digoxin concentrations."	( Evaluation of a computerized digoxin pharmacokinetic consultation service. Jeffrey, LP; Mahoney, CD; Pezzullo, JC; Rich, DS, 1981)	0.87
"This paper reviews the 10 years of providing a Clinical Pharmacokinetic Service (CPS) at the Ottawa General Hospital."	( The history of a comprehensive pharmacokinetic service. Lalonde, R; McLean, W; Roy, M, 1989)	0.28
" Average steady-state Cmax and Ctr were 2-2."	( The effect of bosentan on the pharmacokinetics of digoxin in healthy male subjects. Banken, L; Birnboeck, H; Nave, S; Schulz, R; Weber, C, 1999)	0.56
" The pharmacokinetic parameters of digoxin (AUC0-->24' AUC0-->infinity' Cmax' tmax' t1/2) and cumulative urinary excretion over 120 hours were not affected by the multiple doses of montelukast."	( Effect of multiple doses of montelukast, a CysLT1 receptor antagonist, on digoxin pharmacokinetics in healthy volunteers. De Lepeleire, I; De Schepper, PJ; Depré, M; Freeman, A; Gertz, B; Holland, S; Shahane, A; Van Hecken, A; Verbesselt, R; Wynants, K, 1999)	0.81
" In addition, single-dose pharmacokinetic variables for cerivastatin, including area under the curve (AUC(0-24)), peak concentration (C(max)), time to peak concentration (T(max)), and elimination half-life (t1/2), were examined with and without concurrent digoxin dosing."	( Lack of mutual pharmacokinetic interaction between cerivastatin, a new HMG-CoA reductase inhibitor, and digoxin in healthy normocholesterolemic volunteers. Kaiser, L; Lettieri, JT; Mazzu, AL; Weber, P, 1999)	0.7
"Macrogol 4000 coadministration was associated with a 30% decrease of digoxin AUC and a 40% decrease in its Cmax (P<0."	( Pharmacokinetic and pharmacodynamic drug interactions between digoxin and macrogol 4000, a laxative polymer, in healthy volunteers. Funck-Brentano, C; Jaillon, P; Poirier, JM; Radembino, N; Ragueneau, I; Sao, AB, 1999)	0.78
"0001], peak concentration in plasma (Cmax; P = ."	( Pharmacokinetic interaction of digoxin with an herbal extract from St John's wort (Hypericum perforatum). Bauer, S; Brockmöller, J; Johne, A; Langheinrich, M; Maurer, A; Roots, I, 1999)	0.59
" The objective of this double-blind, randomized, placebo-controlled, 2-way crossover study was to demonstrate the lack of a pharmacokinetic interaction between gemifloxacin and digoxin."	( Lack of pharmacokinetic interaction between gemifloxacin and digoxin in healthy elderly volunteers. Allen, A; Ehren, N; Lewis, A; Vousden, M, )	0.57
"To determine the contribution of the mdr1a gene product to digoxin pharmacokinetics, we constructed a physiologically based pharmacokinetic model for digoxin in mdr1a (-/-) and mdr1a (+/+) mice."	( Physiologically based pharmacokinetics of digoxin in mdr1a knockout mice. Kawahara, M; Miyashita, T; Sakata, A; Tamai, I; Tsuji, A, 1999)	0.81
" There were no significant differences between the pharmacokinetic parameters of repaglinide when given as monotherapy and when administered concurrently with cimetidine."	( Drug interaction studies with repaglinide: repaglinide on digoxin or theophylline pharmacokinetics and cimetidine on repaglinide pharmacokinetics. Hatorp, V; Thomsen, MS, 2000)	0.55
"The reversal effect of itraconazole on P-glycoprotein (P-gp)-mediated resistance of vinblastine, daunorubicin and doxorubicin was analyzed from a cellular pharmacokinetic point of view, namely by [3H]azidopine photoaffinity labeling, intracellular accumulation and transcellular transport experiments."	( Cellular pharmacokinetic aspects of reversal effect of itraconazole on P-glycoprotein-mediated resistance of anticancer drugs. Komada, F; Nishiguchi, K; Okumura, K; Sakaeda, T; Takara, K; Tanigawara, Y, 1999)	0.3
"Digoxin possesses a narrow therapeutic index and shows a large inter-patient pharmacokinetic variability."	( Population pharmacokinetics of digoxin in Korean patients. Derendorf, H; Jeon, S; Nagaraja, NV; Park, YJ; Sands, CD, 2000)	2.04
" The effect of demographic and clinical factors like sex, age, weight, disease state, and renal function on the pharmacokinetic parameters of digoxin was investigated."	( Population pharmacokinetics of digoxin in Korean patients. Derendorf, H; Jeon, S; Nagaraja, NV; Park, YJ; Sands, CD, 2000)	0.79
"A population pharmacokinetic model for the digoxin pharmacokinetics in a section of Korean patients was developed."	( Population pharmacokinetics of digoxin in Korean patients. Derendorf, H; Jeon, S; Nagaraja, NV; Park, YJ; Sands, CD, 2000)	0.86
"The study was carried out to explore the potential for pharmacokinetic interaction of a single oral dose of alpha-dihydroergocryptine (CAS 14271-05-7, DHEC, Almirid) with digoxin."	( Study on the interaction of the dopamine agonist alpha-dihydroergocryptine with the pharmacokinetics of digoxin. Althaus, M; de Mey, C; Mazur, D; Retzow, A; Vens-Cappell, B, 2000)	0.72
"The in vivo digoxin binding affinity and normal pharmacokinetic values of digoxin-immune Fab are unknown."	( Comparison of the pharmacokinetics and in vivo bioaffinity of DigiTAb versus Digibind. Sjostrom, L; Ujhelyi, MR; Ward, SB, 2000)	0.69
" The pharmacokinetic parameters were calculated using a noncompartmental analysis."	( Pharmacokinetics of intravenously administered digoxin and histopathological picture in rabbits with experimental bile duct obstruction. Drozdzik, M; Gawrońska-Szklarz, B; Rózewicka, L; Sulikowski, T; Wójcicki, J; Wójcicki, M; Zieliński, S, 2000)	0.56
" No statistically significant differences between treatment groups were observed for any of the calculated digoxin pharmacokinetic parameters."	( Effect of rofecoxib on the pharmacokinetics of digoxin in healthy volunteers. De Smet, M; Ebel, DL; Gertz, BJ; Larson, PJ; Lens, S; Lins, R; Porras, AG; Schwartz, JI; Verbesselt, R, 2001)	0.78
" Blood samples were obtained on days 3, 5, 8, 9, and 14, and serum digoxin concentration data were analyzed by model-independent pharmacokinetic methods."	( Effect of zaleplon on digoxin pharmacokinetics and pharmacodynamics. Darwish, M; Frías, J; García Pérez, LE; Guerra, P; Leister, CA; Paty, I; Sanchez Garcia, P, 2000)	0.86
" Five days of dofetilide treatment did not significantly affect steady-state pharmacokinetic variables of digoxin compared with placebo; therefore, the use of dofetilide does not necessitate an adjustment in digoxin dose to maintain therapeutic digoxin levels."	( Effect of dofetilide on the pharmacokinetics of digoxin. Dalrymple, I; Kleinermans, D; Nichols, DJ, 2001)	0.78
" Geometric mean AUC144-168, Cmax, and Cmin values for digoxin when given in combination with telmisartan were higher by 22%, 50%, and 13%, respectively, compared with values when given alone."	( The effect of telmisartan on the steady-state pharmacokinetics of digoxin in healthy male volunteers. Hendriks, MG; Jonkman, JH; Oosterhuis, B; Sollie, FA; Stangier, J; Su, CA; van Lier, JJ, 2000)	0.79
" The pharmacokinetic profiles of digoxin and warfarin were not altered by the simultaneous and continued administration of sevelamer."	( Sevelamer hydrochloride (Renagel), a nonabsorbed phosphate-binding polymer, does not interfere with digoxin or warfarin pharmacokinetics. Amin, N; Burke, S; Incerti, C; Plone, M; Watson, N, 2001)	0.81
" There were no statistically significant differences in any of the digoxin pharmacokinetic parameters (AUC(0-->24), AUC(0-->infinity), Cmax, tmax, t(1/2), CL/F, CLrenal, and Ae(0-->infinity)), and the 90% confidence intervals for treatment differences for the parameters (except for tmax) were all within 80% to 125%."	( Lack of citalopram effect on oral digoxin pharmacokinetics. Larsen, F; Overø, KF; Priskorn, M, 2001)	0.83
" Analysis of the pharmacokinetics of digoxin was accomplished using a simple steady-state pharmacokinetic model."	( Population-based investigation of relative clearance of digoxin in Japanese neonates and infants by multiple-trough screen analysis. Goto, Y; Higuchi, S; Minemoto, M; Ohdo, S; Suematsu, F; Yukawa, E; Yukawa, M, 2001)	0.83
" Blood and urine samples were collected at appropriate times for evaluation of digoxin and cilomilast steady-state pharmacokinetic parameters."	( Cilomilast: pharmacokinetic and pharmacodynamic interactions with digoxin. Clark, DJ; Collie, H; Kelly, J; Murdoch, RD; Schubert, C; Zussman, BD, 2001)	0.78
" At steady state, cilomilast 15 mg BID had no significant effect on the steady-state pharmacokinetic parameters of digoxin, with 90% CIs for both primary end points--area under the plasma concentration-time curve (AUC) over a 24-hour dosing interval and minimum plasma concentration--completely contained within the specified interval for equivalence (0."	( Cilomilast: pharmacokinetic and pharmacodynamic interactions with digoxin. Clark, DJ; Collie, H; Kelly, J; Murdoch, RD; Schubert, C; Zussman, BD, 2001)	0.76
"This study was undertaken to determine whether levetiracetam (Keppra) affected the pharmacokinetic or pharmacodynamic profile of digoxin in healthy adults."	( Repeated administration of the novel antiepileptic agent levetiracetam does not alter digoxin pharmacokinetics and pharmacodynamics in healthy volunteers. Baltes, E; Levy, RH; Ragueneau-Majlessi, I, 2001)	0.74
" Although digoxin produced predictable changes in ECG, its pharmacodynamic parameters did not differ significantly between levetiracetam and placebo administration."	( Repeated administration of the novel antiepileptic agent levetiracetam does not alter digoxin pharmacokinetics and pharmacodynamics in healthy volunteers. Baltes, E; Levy, RH; Ragueneau-Majlessi, I, 2001)	0.94
"At the doses administered, there was no pharmacokinetic interaction and no evidence of a pharmacodynamic interaction between digoxin and levetiracetam."	( Repeated administration of the novel antiepileptic agent levetiracetam does not alter digoxin pharmacokinetics and pharmacodynamics in healthy volunteers. Baltes, E; Levy, RH; Ragueneau-Majlessi, I, 2001)	0.74
" The secondary objective was to determine whether the magnitude of the pharmacokinetic interaction was influenced by P-glycoprotein genetic polymorphism."	( Effect of grapefruit juice on digoxin pharmacokinetics in humans. Becquemont, L; Brinkmann, U; Funck-Brentano, C; Jaillon, P; Kerb, R; Lebot, M; Verstuyft, C, 2001)	0.6
" No relationship between MDR1 C3435T genotype and early digoxin pharmacokinetic changes could be detected."	( Effect of grapefruit juice on digoxin pharmacokinetics in humans. Becquemont, L; Brinkmann, U; Funck-Brentano, C; Jaillon, P; Kerb, R; Lebot, M; Verstuyft, C, 2001)	0.85
"To clarify the observed variability of digoxin disposition by performing a population pharmacokinetic analysis in a Japanese population."	( Population pharmacokinetics of digoxin in Japanese patients: a 2-compartment pharmacokinetic model. Aoyama, T; Goto, Y; Higuchi, S; Minemoto, M; Ohdo, S; Suematu, F; Yukawa, E; Yukawa, M, 2001)	0.87
"Retrospective analysis of clinical pharmacokinetic data."	( Population pharmacokinetics of digoxin in Japanese patients: a 2-compartment pharmacokinetic model. Aoyama, T; Goto, Y; Higuchi, S; Minemoto, M; Ohdo, S; Suematu, F; Yukawa, E; Yukawa, M, 2001)	0.6
" Population pharmacokinetic analysis was performed using a 2-compartment open pharmacokinetic model with the computer program NONMEM."	( Population pharmacokinetics of digoxin in Japanese patients: a 2-compartment pharmacokinetic model. Aoyama, T; Goto, Y; Higuchi, S; Minemoto, M; Ohdo, S; Suematu, F; Yukawa, E; Yukawa, M, 2001)	0.6
" Final pharmacokinetic parameters were: CL (L/h) = (0."	( Population pharmacokinetics of digoxin in Japanese patients: a 2-compartment pharmacokinetic model. Aoyama, T; Goto, Y; Higuchi, S; Minemoto, M; Ohdo, S; Suematu, F; Yukawa, E; Yukawa, M, 2001)	0.6
"Results of this study suggest that an important pharmacokinetic interaction between levofloxacin and digoxin is unlikely to occur when administered concomitantly."	( Absence of a pharmacokinetic interaction between digoxin and levofloxacin. Chien, SC; Chow, AT; Natarajan, J; Rogge, MC; Williams, RR; Wong, F, 2002)	0.78
"8 mg) affects the pharmacokinetic and safety profile of intravenous digoxin (0."	( Effects of the concomitant administration of tamsulosin (0.8 mg) on the pharmacokinetic and safety profile of intravenous digoxin (Lanoxin) in normal healthy subjects: a placebo-controlled evaluation. Forrest, A; Ito, Y; Kamimura, H; Miyazawa, Y; Paul Starkey, L; Schentag, JJ; Swarz, H, 2002)	0.76
" Digoxin clearance was calculated using a pharmacokinetic software package."	( Serum cystatin C is not a better marker of creatinine or digoxin clearance than serum creatinine. Brice, S; Jackson, SH; O'Riordan, S; Ouldred, E; Swift, CG, 2002)	1.47
" On the other hand isosorbide dinitrate significantly increased digoxin maximum serum concentration but without change in the other digoxin pharmacokinetic parameters."	( A comparison between the effects of diltiazem and isosorbide dinitrate on digoxin pharmacodynamics and kinetics in the treatment of patients with chronic ischemic heart failure. Abdulatif, AS; El-Medany, AH; Mahgoub, AA, 2002)	0.78
"There were no differences in the pharmacokinetic parameters of digoxin in the two periods, apart from a significant increase in the mean maximum serum concentration (Cmax) when digoxin was given with acarbose (5."	( Do therapeutic doses of acarbose alter the pharmacokinetics of digoxin? Almog, S; Cohen, E; Garty, M; Staruvin, D, 2002)	0.79
"There was no significant pharmacokinetic interaction between digoxin and acarbose at current therapeutic doses in the healthy volunteers."	( Do therapeutic doses of acarbose alter the pharmacokinetics of digoxin? Almog, S; Cohen, E; Garty, M; Staruvin, D, 2002)	0.8
"Digoxin pharmacokinetics were studied in a pediatric population with an age range of 6 days to 1 year using the population pharmacokinetic approach."	( Population pharmacokinetics of digoxin in pediatric patients. Arranz, I; Falcao, AC; González, MC; Hernández, FJ; Lanao, JM; Martín-Suárez, A; Outeda, M; Quero, M, 2002)	2.04
" The geometric least square mean AUC(0-t) and Cmax of digoxin were only 4% higher when the drug was coadministered with rosuvastatin compared to placebo."	( No effect of rosuvastatin on the pharmacokinetics of digoxin in healthy volunteers. Dane, AL; Kemp, J; Martin, PD; Schneck, DW; Warwick, MJ, 2002)	0.81
" We assessed whether teriparatide causes a change in digoxin pharmacodynamic effects by measuring systolic time intervals and heart rate."	( Teriparatide has no effect on the calcium-mediated pharmacodynamics of digoxin. Benson, CT; Voelker, JR, 2003)	0.8
"A PK/PD model for the relationship between the plasma concentration of digoxin, the estimated concentration at the effect site and the reduction in heart rate during atrial fibrillation could be defined using a population pharmacokinetic approach."	( Intravenously administered digoxin in patients with acute atrial fibrillation: a population pharmacokinetic/pharmacodynamic analysis based on the Digitalis in Acute Atrial Fibrillation trial. Held, P; Hornestam, B; Jerling, M; Karlsson, MO, 2003)	0.85
"This study demonstrates a pharmacokinetic and pharmaceutic interaction between the emulgent Cremophor RH40 and digoxin, caused by P-glycoprotein inhibition and prolongation of the dissolution time of digoxin tablets by Cremophor RH40, respectively."	( Pharmacokinetic and pharmaceutic interaction between digoxin and Cremophor RH40. Burhenne, J; Ding, R; Haefeli, WE; Hoppe-Tichy, T; Mikus, G; Riedel, KD; Tayrouz, Y; Weiss, J, 2003)	0.78
"To investigate the effect of Shengmai Injection (SMI) on serum concentration and pharmacokinetic parameters of digoxin in patients with congestive heart failure."	( [Clinical study on effect of shengmai injection on serum concentration and pharmacokinetic parameters of digoxin in patients with congestive heart failure]. Mao, JY; Wang, HH; Xu, WR, 2003)	0.74
" The serum concentration of digoxin at different time points was determined with radioimmunoassay and the pharmacokinetical parameters were calculated with 3P97 pharmacokinetic software."	( [Clinical study on effect of shengmai injection on serum concentration and pharmacokinetic parameters of digoxin in patients with congestive heart failure]. Mao, JY; Wang, HH; Xu, WR, 2003)	0.83
"A study was carried out to evaluate the potential pharmacokinetic interaction between digoxin and acenocoumarol."	( Pharmacokinetic study of the digoxin-acenocoumarol interaction in rabbits. Alberca, I; Atencio, DR; Lanao, JM; Lopez, FG; Martin-Suarez, A; Mendez, ME; Santos, M; Zarzuelo, A, 2003)	0.83
" a one-, two- or three-compartment pharmacokinetic model)."	( Population pharmacokinetics of levosimendan in patients with congestive heart failure. Antila, S; Jonsson, EN; Karlsson, MO; Lehtonen, L; McFadyen, L, 2003)	0.32
"Concomitant administration with voriconazole did not significantly alter the Cmax, AUCtau, tmax or CLR of digoxin at steady state."	( Voriconazole does not affect the steady-state pharmacokinetics of digoxin. Kleinermans, D; Nichols, D; Purkins, L; Wood, N, 2003)	0.77
" The pharmacokinetic properties of digoxin after oral administration of its hydroxypropyl-beta-cyclodextrin (HPCD) inclusion complex to rabbits and human volunteers were investigated in comparison with those of commercially available tablets."	( Effects of 2-hydroxypropyl-beta-cyclodextrin on pharmacokinetics of digoxin in rabbits and humans. He, ZG; Li, YS; Tang, X; Zhang, RH; Zhang, TH; Zhao, C, 2004)	0.84
"Pharmacokinetic parameters showed extensive variation; median values were: elimination half-life 42."	( Pharmacokinetics of digoxin in children with congestive heart failure aggravated by other diseases. Bobadilla-Chávez, J; Flores-Pérez, J; Juárez-Olguín, H; Lares-Asseff, I, )	0.45
"The range of dosage required in order to adjust individual treatments was very wide, leading us to the conclusion that therapeutic schemes for this population should be individualized based on their pharmacokinetic parameters, and therapeutic monitoring of drugs should be performed."	( Pharmacokinetics of digoxin in children with congestive heart failure aggravated by other diseases. Bobadilla-Chávez, J; Flores-Pérez, J; Juárez-Olguín, H; Lares-Asseff, I, )	0.45
" Digoxin pharmacokinetic parameter values were determined using noncompartmental methods."	( Ritonavir decreases the nonrenal clearance of digoxin in healthy volunteers with known MDR1 genotypes. Alfaro, RM; Falloon, J; Natarajan, V; Penzak, SR; Remaley, AT; Shen, JM, 2004)	1.49
" The aim of the study was to evaluate the possible pharmacokinetic interaction of marketed St John's wort formulations and doses with digoxin."	( Effect of St John's wort dose and preparations on the pharmacokinetics of digoxin. Drewelow, B; Frank, B; Hehl, EM; Majcher-Peszynska, J; Mueller, SC; Petzsch, M; Riethling, AK; Sievers, H; Uehleke, B; Woehling, H, 2004)	0.76
" In conclusion, no pharmacokinetic or pharmacodynamic interaction between digoxin and ximelagatran was observed in this study."	( No pharmacokinetic or pharmacodynamic interaction between digoxin and the oral direct thrombin inhibitor ximelagatran in healthy volunteers. Eriksson, UG; Kessler, E; Sarich, TC; Schützer, KM; Wall, U; Wollbratt, M, 2004)	0.8
" We examined digoxin transport in the presence and absence of ouabain to determine whether digoxin binding to Na+,K(+)-ATPase affects its transcellular digoxin transport, and evaluated its influx and efflux clearance by model-dependent pharmacokinetic analysis."	( Pharmacokinetic characterization of transcellular transport and drug interaction of digoxin in Caco-2 cell monolayers. Aiba, T; Hashimoto, Y; Ishida, K; Okuno, M; Yoshinaga, M, 2005)	0.92
" The Tmax and mean residence time (MRT) values of digoxin pharmacokinetics in four subjects with drowsiness were significantly lower and Cmax was higher than those in four subjects with marginal effect."	( Relationship between loperamide-induced sedative effect and digoxin pharmacokinetics in healthy Japanese subjects. Aungst, BJ; Fujita, H; Kobayashi, M; Matsubara, K; Saito, T; Saitoh, H; Suno, M; Yamaguchi, M, 2005)	0.82
" The pharmacokinetic and pharmacodynamic changes observed upon coadministration were small and are not expected to be clinically important."	( Influence of coadministration on the pharmacokinetics of azimilide dihydrochloride and digoxin. Agnew, JR; Corey, AE; Moehrke, W; Parekh, N; Powell, JH; Thompson, GA; Toothaker, RD; Valentine, SN, 2005)	0.55
"), respectively, showed significant change of the pharmacokinetic parameters of Dx compared with the control rats."	( Pharmacokinetic interaction with digoxin and glucocorticoids in rats detected by radio-immunoassay using a novel specific antiserum. Fujii, Y; Higashi, Y; Ikeda, Y; Yamamoto, R; Yamashiro, M, 2005)	0.61
" Digoxin urinary pharmacokinetic parameters were not altered."	( Effect of exenatide on the steady-state pharmacokinetics of digoxin. Chan, C; Kothare, PA; Lim, M; Linnebjerg, H; Mace, KF; Park, S; Soon, DK; Wise, SD; Yeo, A, 2005)	1.48
" Comparisons of area under the serum concentration time curves from 0 to 3 h (AUC(0-3)), AUC(0-24), Cmax, apparent oral clearance of digoxin (CL/F), and elimination half-life were used to assess the effects of milk thistle, black cohosh, rifampin, and clarithromycin on digoxin pharmacokinetics."	( Effect of milk thistle (Silybum marianum) and black cohosh (Cimicifuga racemosa) supplementation on digoxin pharmacokinetics in humans. Barone, GW; Breen, P; Carrier, J; Cheboyina, S; Gurley, BJ; Hubbard, MA; Song, PF; Tong, Y; Williams, DK; Yates, CR, 2006)	0.75
" Because digoxin is distributed to lean body mass, use of the BMI could have overadjusted body weight, leading to inaccurate pharmacokinetic assumptions and calculations."	( Evaluation of a sex-based difference in the pharmacokinetics of digoxin. Chan, LN; Lee, LS, 2006)	0.99
" This article utilized the physiologically based pharmacokinetic (PBPK) liver model and its extension that include heterogeneity in enzymes and transporters to illustrate how in vitro uptake and metabolic data from zonal hepatocytes on transport and enzymes may be used to predict the kinetics of removal in the intact liver; binding data were also necessary."	( An integrated approach to model hepatic drug clearance. Liu, L; Pang, KS, 2006)	0.33
" The potential for pharmacokinetic and/or pharmacodynamic interactions between solifenacin and warfarin or digoxin was investigated."	( Multiple doses of the antimuscarinic agent solifenacin do not affect the pharmacodynamics or pharmacokinetics of warfarin or the steady-state pharmacokinetics of digoxin in healthy subjects. Krauwinkel, WJ; Kuipers, ME; Smulders, RA, 2006)	0.74
" No significant changes in mean residence time and terminal half-life were observed for all drugs, suggesting a negligible effect of BA on their hepatic/renal elimination."	( Altered oral bioavailability and pharmacokinetics of P-glycoprotein substrates by coadministration of biochanin A. Cousineau, M; Danser, E; Dewire, R; Floden, J; Peng, SX; Ritchie, DM, 2006)	0.33
" There was a significant decrease in elimination half-life (P<0."	( The effect of pancreatic and biliary depletion on the in vivo pharmacokinetics of digoxin in pigs. Erlwanger, K; Evilevitch, L; Lennernäs, H; Piedra, JV; Pierzynowski, S; Tannergren, C; Tatara, M; Weström, B, 2006)	0.56
" Comparisons of area under the curve (AUC)((0-3)), AUC((0-24)), C(max,) CL/F, and elimination half-life were used to assess the effects of goldenseal, kava kava, rifampin, and clarithromycin on digoxin pharmacokinetics."	( Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans. Barone, GW; Breen, P; Cheboyina, S; Gurley, BJ; Hubbard, MA; Stuart, LB; Swain, A; Tong, Y; Williams, DK; Yates, CR, 2007)	0.75
" The apparent terminal half-life was highly variable, with a median time of 42."	( Pharmacokinetics of digoxin cross-reacting substances in patients with acute yellow Oleander (Thevetia peruviana) poisoning, including the effect of activated charcoal. Buckley, NA; Eddleston, M; Potter, JM; Roberts, DM; Roberts, MS; Southcott, E, 2006)	0.66
" Two pharmacokinetic factors appear to be of major concern, namely the age-related decrease renal function and changes in drug metabolism and distribution."	( [Pharmacokinetics of cardiovascular drugs in the elderly]. Imbs, JL; Lates, S; Welsch, M, )	0.13
" The objective of this work was to apply different methods for covariate selection in non-linear mixed-effect models to study the relationship between the pharmacokinetic parameters of digoxin and the genotype for two major exons located on the multi-drug-resistance 1 (MDR1) gene coding for P-glycoprotein."	( Modelling the influence of MDR1 polymorphism on digoxin pharmacokinetic parameters. Becquemont, L; Comets, E; Jaillon, P; Lavielle, M; Mentré, F; Verstuyft, C, 2007)	0.79
"Thirty-two healthy volunteers were recruited in three pharmacokinetic drug interaction studies."	( Modelling the influence of MDR1 polymorphism on digoxin pharmacokinetic parameters. Becquemont, L; Comets, E; Jaillon, P; Lavielle, M; Mentré, F; Verstuyft, C, 2007)	0.6
" Non-linear mixed-effect models can be useful for detecting the influence of covariates on pharmacokinetic parameters."	( Modelling the influence of MDR1 polymorphism on digoxin pharmacokinetic parameters. Becquemont, L; Comets, E; Jaillon, P; Lavielle, M; Mentré, F; Verstuyft, C, 2007)	0.6
" When rats were subcutaneously administered PCN, an increase of biliary excretion clearance and distribution volume was observed for drugs such as MPP(+), metformin, and tetraethylammonium, although the effects on pharmacokinetic parameters were variable among the tested drugs."	( Effect of pregnane X receptor ligand on pharmacokinetics of substrates of organic cation transporter Oct1 in rats. Higashi, R; Maeda, T; Nagata, K; Oyabu, M; Tamai, I; Yamazoe, Y; Yotsumoto, T, 2007)	0.34
" Analysis of the pharmacokinetics of digoxin was accomplished using a one-compartment open pharmacokinetic model."	( Population pharmacokinetic investigation of digoxin in Japanese neonates. Akiyama, K; Minemoto, M; Suematsu, F; Yukawa, E; Yukawa, M, 2007)	0.87
" This open-label, randomized, 3-period crossover study investigated the potential for pharmacokinetic interactions in 18 healthy subjects during coadministration of vildagliptin and digoxin."	( Evaluation of pharmacokinetic interactions between vildagliptin and digoxin in healthy volunteers. Bizot, MN; Dole, WP; He, YL; Howard, D; Leon, S; Ligueros-Saylan, M; Riviere, GJ; Sabo, R; Sunkara, G, 2007)	0.77
" The data were evaluated using a mechanistic pharmacokinetic approach in NONMEM."	( Pharmacodynamics of carbamazepine-mediated induction of CYP3A4, CYP1A2, and Pgp as assessed by probe substrates midazolam, caffeine, and digoxin. Cederberg, J; Dahl, ML; Karlsson, MO; Magnusson, MO; Sandström, R, 2008)	0.55
" The aims of this study were to elucidate its pharmacokinetic characteristics, tissue distribution, plasma protein binding and excretion properties and underlying mechanisms of deuxemether in rats based on the simultaneous determination of MHD and DMD."	( Pharmacokinetics, tissue distribution and excretion of a new photodynamic drug deuxemether. Hao, H; He, H; Li, X; Wang, G; Wang, R; Wang, W; Xie, H; Xu, M, 2008)	0.35
" pharmacokinetic data on 670 drugs representing, to our knowledge, the largest publicly available set of human clinical pharmacokinetic data."	( Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds. Lombardo, F; Obach, RS; Waters, NJ, 2008)	0.35
"This study investigated the potential pharmacokinetic interaction between the direct renin inhibitor aliskiren and modulators of P-glycoprotein and cytochrome P450 3A4 (CYP3A4)."	( Pharmacokinetics of the oral direct renin inhibitor aliskiren in combination with digoxin, atorvastatin, and ketoconazole in healthy subjects: the role of P-glycoprotein in the disposition of aliskiren. Bizot, MN; Camenisch, G; Dieterich, HA; Dole, WP; Howard, D; Reynolds, C; Schuetz, H; Vaidyanathan, S; Yeh, CM, 2008)	0.57
" The aim of this exploratory study was to assess the hemodynamic and pharmacokinetic interactions between digoxin and oral levosimendan as well as the proarrhythmic potential of this combination in patients with chronic heart failure."	( The hemodynamic and pharmacokinetic interactions between chronic use of oral levosimendan and digoxin in patients with NYHA Classes II-III heart failure. Harjola, VP; Jurkko, R; Nieminen, MS; Oikarinen, L; Puttonen, J; Sarapohja, T; Sundberg, S; Toivonen, L, 2008)	0.78
" Pharmacokinetic variables of levosimendan and digoxin were calculated in both treatment periods."	( The hemodynamic and pharmacokinetic interactions between chronic use of oral levosimendan and digoxin in patients with NYHA Classes II-III heart failure. Harjola, VP; Jurkko, R; Nieminen, MS; Oikarinen, L; Puttonen, J; Sarapohja, T; Sundberg, S; Toivonen, L, 2008)	0.82
" In contrast to the earlier data with intravenous levosimendan, the results indicate a pharmacokinetic interaction between levosimendan and digoxin."	( The hemodynamic and pharmacokinetic interactions between chronic use of oral levosimendan and digoxin in patients with NYHA Classes II-III heart failure. Harjola, VP; Jurkko, R; Nieminen, MS; Oikarinen, L; Puttonen, J; Sarapohja, T; Sundberg, S; Toivonen, L, 2008)	0.77
" Venous blood samples were taken from 0 to 4 h after dosing, and the pharmacokinetic parameters were calculated using the Drug and Statistics software."	( Impact of MDR1 haplotypes derived from C1236T, G2677T/A and C3435T on the pharmacokinetics of single-dose oral digoxin in healthy Chinese volunteers. Jiang, ZP; Li, HD; Tu, JY; Xu, P; Zhang, BK, 2008)	0.56
" The peak concentration in plasma, the time to reach the peak concentration and the area under the plasma concentration/time curve between 0 and 4 h were used as indices of digoxin absorption."	( Impact of MDR1 haplotypes derived from C1236T, G2677T/A and C3435T on the pharmacokinetics of single-dose oral digoxin in healthy Chinese volunteers. Jiang, ZP; Li, HD; Tu, JY; Xu, P; Zhang, BK, 2008)	0.75
" Pharmacokinetic parameters assessed at the end of each treatment period were compared using the standard statistical analysis for bioequivalence assessment."	( Absence of an effect of a single-dose deferasirox on the steady-state pharmacokinetics of digoxin. Balez, S; Belleli, R; Robeva, A; Sechaud, R, 2008)	0.57
" The developed assay method was successfully applied to a pharmacokinetic study in human volunteers following intravenous administration of digoxin."	( Development and validation of an LC-MS method with electrospray ionization for quantitation of digoxin in human plasma and urine: application to a pharmacokinetic study. Chen, H; Li, Z; Shi, S; Zeng, F, 2008)	0.77
" This study was designed to establish if this combination of therapy has the potential of a significant pharmacokinetic interaction."	( Pharmacokinetics of digoxin in healthy subjects receiving taranabant, a novel cannabinoid-1 receptor inverse agonist. Denker, AE; Dunbar, S; Lewis, NM; Li, S; Morelli, G; Taggart, W; Vessey, LK; Wagner, JA; Yuan, J, 2009)	0.68
"To determine the digoxin population pharmacokinetic parameters and influence of various factors on pharmacokinetic parameters in Thai pediatric patients with heart disease."	( Population pharmacokinetics of digoxin in Thai pediatric patients. Petcharattana, S; Preechagoon, Y; Somsaard, P, 2009)	0.98
"The present study was an analytical cross-sectional study design and population pharmacokinetic modeling study."	( Population pharmacokinetics of digoxin in Thai pediatric patients. Petcharattana, S; Preechagoon, Y; Somsaard, P, 2009)	0.64
" Median time of occurrence of C(max) and mean half-life of immunoreactive digoxin were comparable in the presence and absence of laropiprant."	( Effects of laropiprant, a selective prostaglandin D2 receptor 1 antagonist, on the steady-state pharmacokinetics of digoxin in healthy adult subjects. Buckland, M; Connolly, S; Denker, A; Johnson-Levonas, AO; Lai, E; Liu, F; Vessey, L; Wagner, JA; Wenning, L, 2010)	0.8
" However, elimination rate (k(e)) and half-life (t(1/2)) in rats reperfused for 1 h were not altered."	( Pharmacokinetics of oral and intravenous administration of digoxin after intestinal ischemia-reperfusion. Iseki, K; Itagaki, S; Kobayashi, M; Maruyama, H; Ogura, J, 2010)	0.6
"To establish a population pharmacokinetic (PPK) model of digoxin in older Chinese patients to provide a reference for individual medication in clinical practice."	( Population pharmacokinetic model of digoxin in older Chinese patients and its application in clinical practice. Gao, Y; Guan, Z; Li, J; Li, ZD; Zhou, XD, 2010)	0.88
" Analysis of the pharmacokinetics of digoxin was accomplished using a 1-compartment pharmacokinetic model."	( Population pharmacokinetic investigation of digoxin in Japanese infants and young children. Aki, H; Ikeda, H; Mimemoto, M; Suematsu, F; Takiguchi, T; Yukawa, E; Yukawa, M, 2011)	0.9
" Because a patient taking digoxin may also take hawthorn, we investigated potential interference of hawthorn in serum digoxin measurements using immunoassays as well as pharmacodynamic interaction between hawthorn and digoxin."	( Interference of hawthorn on serum digoxin measurements by immunoassays and pharmacodynamic interaction with digoxin. Bick, RJ; Dasgupta, A; Kidd, L; Poindexter, BJ, 2010)	0.94
"To study potential pharmacodynamic interaction between hawthorn and digoxin."	( Interference of hawthorn on serum digoxin measurements by immunoassays and pharmacodynamic interaction with digoxin. Bick, RJ; Dasgupta, A; Kidd, L; Poindexter, BJ, 2010)	0.88
" To study the pharmacodynamic interaction between hawthorn and digoxin, we used an isolated adult rat cardiomyocyte system, measuring calcium transients by real-time fluorescence spectrophotometry."	( Interference of hawthorn on serum digoxin measurements by immunoassays and pharmacodynamic interaction with digoxin. Bick, RJ; Dasgupta, A; Kidd, L; Poindexter, BJ, 2010)	0.88
"Because of interference of hawthorn with a digoxin immunoassay and pharmacodynamic interaction with digoxin, a patient receiving digoxin should avoid hawthorn."	( Interference of hawthorn on serum digoxin measurements by immunoassays and pharmacodynamic interaction with digoxin. Bick, RJ; Dasgupta, A; Kidd, L; Poindexter, BJ, 2010)	0.9
"Hyperthyroid patients showed significantly lower serum digoxin concentrations, shorter T1/2 beta and a significantly smaller area under the concentration curve (AUC) that the control group."	( [Pharmacokinetics of digoxin in hyperthyroidism. Effect of methimazole]. Dec, R; Gasińska, T; Izbicka, M, 2010)	0.93
" The validated method was applied to the pharmacokinetic study of periplocin in rat plasma after intravenous and intramuscular administration."	( Determination and pharmacokinetics of periplocin in rat plasma by LC-MS. Bi, K; Che, S; Chen, X; Liu, W; Lu, D; Yi, L; Zhang, Q, 2010)	0.36
"The low-, medium- and high-dose SMI showed different effects on the pharmacokinetics of digoxin: the low-, medium- and high-dose SMI revealed a tendency to decrease the elimination half-life (T(1/2β)) of digoxin."	( [Effects of Shenmai Injection on serum concentration and pharmacokinetics of digoxin in dogs with heart failure]. Bi, YF; Liu, CX; Mao, JY; Wang, HH; Wang, XL; Wei, GL; Xing, J; Zhang, ZP, 2010)	0.81
" Plasma samples for pharmacokinetic evaluations of digoxin and roflumilast concentrations with and without concomitant treatment were taken."	( Absence of pharmacokinetic interaction between roflumilast and digoxin in healthy adults. Bethke, TD; Eckermann, G; Lahu, G; Nassr, N, 2012)	0.87
" Based on numerous reports implicating the role of the ATP-binding cassette drug transporter P-glycoprotein (P-gp) in ivermectin efflux in dogs, an in vivo study was conducted to determine whether ivermectin toxicity results from a pharmacokinetic interaction with spinosad."	( Pharmacokinetic interaction of the antiparasitic agents ivermectin and spinosad in dogs. Balogh, L; Dunn, ST; Hedges, L; Lai, Y; Locuson, CW; Mahabir, S; Sampson, KE, 2011)	0.37
" There were no clinically significant changes in steady-state pharmacokinetic parameters of digoxin when it was co-administered with linagliptin."	( Evaluation of the pharmacokinetic interaction after multiple oral doses of linagliptin and digoxin in healthy volunteers. Brand, T; Friedrich, C; Graefe-Mody, EU; Ring, A; Sennewald, R; Woerle, HJ, 2011)	0.81
" Because use of more than 1 drug is often required with these conditions, pharmacokinetic considerations, including those related to complementary medicine, are important."	( Digoxin therapy in the elderly: pharmacokinetic considerations in nursing. Jelinek, HF; Warner, P, )	1.57
" Pharmacokinetic calculations were performed on each individual set of data using 3P97 practical pharmacokinetic software."	( [Effect of berberine on pharmacokinetics of digoxin after oral administration to rats]. Jiang, X; Ju, Y; Liu, C; Qiu, W, 2011)	0.63
" After pretreatment with BBR (30, 100 mg x kg(-1)), the pharmacokinetic parameters of ig DIG were significantly altered."	( [Effect of berberine on pharmacokinetics of digoxin after oral administration to rats]. Jiang, X; Ju, Y; Liu, C; Qiu, W, 2011)	0.63
" The pharmacokinetic profile of digoxin also remained unchanged in the presence of dabigatran etexilate."	( Pharmacokinetics and pharmacodynamics of dabigatran etexilate, an oral direct thrombin inhibitor, with coadministration of digoxin. Körnicke, T; Rathgen, K; Reseski, K; Roth, W; Stähle, H; Stangier, J, 2012)	0.87
" However, because of sampling restrictions, it is often difficult to perform traditional pharmacokinetic studies in elderly patients."	( Determination of digoxin clearance in Japanese elderly patients for optimization of drug therapy: a population pharmacokinetics analysis using nonlinear mixed-effects modelling. Aki, H; Ikeda, H; Mimemoto, M; Suematsu, F; Takiguchi, T; Yukawa, E; Yukawa, M, 2011)	0.71
" Midazolam, 1'-hydroxymidazolam, digoxin, and telaprevir concentrations in plasma and digoxin concentrations in urine were measured and pharmacokinetic parameters calculated."	( Effect of telaprevir on the pharmacokinetics of midazolam and digoxin. Alves, K; Chandorkar, G; Farmer, HF; Garg, V; Smith, F; van Heeswijk, RP, 2012)	0.9
" Blood samples for pharmacokinetic profiling were taken up to 72 h post-dose and digoxin plasma concentrations were determined by a validated liquid chromatography-tandem mass spectrometry (LCMS/MS) method."	( Pharmacokinetics and bioequivalence study of two digoxin formulations after single-dose administration in healthy Chinese male volunteers. Cao, XM; Rui, JZ; Tian, Y; Zhang, XY; Zhang, ZJ, 2011)	0.85
" The aim of these studies was to assess the potential for pharmacokinetic interaction between dapagliflozin, a sodium glucose co-transporter-2 inhibitor being developed for the treatment of T2DM, and four medications commonly prescribed in patients with T2DM and cardiovascular disease: simvastatin, valsartan, warfarin, and digoxin."	( Lack of pharmacokinetic interactions between dapagliflozin and simvastatin, valsartan, warfarin, or digoxin. Boulton, DW; Chang, M; Griffen, SC; Kasichayanula, S; LaCreta, FP; Liu, X; Shyu, WC, 2012)	0.77
"Potential pharmacokinetic interactions between 20 mg dapagliflozin, 40 mg simvastatin, or 320 mg valsartan were assessed in an open-label, randomized, five-period, five-treatment, unbalanced crossover study in 24 healthy subjects."	( Lack of pharmacokinetic interactions between dapagliflozin and simvastatin, valsartan, warfarin, or digoxin. Boulton, DW; Chang, M; Griffen, SC; Kasichayanula, S; LaCreta, FP; Liu, X; Shyu, WC, 2012)	0.6
" Further studies indicated stereoselective pharmacokinetic profiles and intestinal biotransformations of Rh2 epimers."	( Stereoselective regulations of P-glycoprotein by ginsenoside Rh2 epimers and the potential mechanisms from the view of pharmacokinetics. Lu, M; Niu, F; Sun, J; Wang, G; Wu, X; Zhang, J; Zhou, F, 2012)	0.38
"Population pharmacokinetic and dynamic modeling is often employed to analyze data of steady-state trough serum digoxin concentrations in the course of what is frequently regarded as routine therapeutic drug monitoring (TDM)."	( Some comments and suggestions concerning population pharmacokinetic modeling, especially of digoxin, and its relation to clinical therapy. Jelliffe, RW, 2012)	0.81
"This study was designed to characterize breast cancer resistance protein (Bcrp) knockout Abcg2(-/-) rats and assess the effect of ATP-binding cassette subfamily G member 2 (Abcg2) deletion on the excretion and pharmacokinetic properties of probe substrates."	( Deletion of Abcg2 has differential effects on excretion and pharmacokinetics of probe substrates in rats. Be, X; Colletti, AE; Huang, L; Jin, L; Langley, M; Ling, Y; Roberts, J; Tchaparian, EH; Wong, BK, 2012)	0.38
"This study was aimed at determining the population pharmacokinetics of digoxin and identifying factors that explain pharmacokinetic variability in elderly patients."	( Population pharmacokinetics of digoxin in elderly patients. Chen, R; Jiang, Y; Qian, CY; Wang, ML; Xia, ZL; Xue, H; Zou, SL, 2013)	0.91
" Apparent permeability values and pharmacokinetic parameters of digoxin were compared to determine if co-administration of digoxin with ML, CP, or VA modulated the activity of P-gp."	( Ex vivo and in vivo investigations of the effects of extracts of Vernonia amygdalina, Carica papaya and Tapinanthus sessilifolius on digoxin transport and pharmacokinetics: assessing the significance on rat intestinal P-glycoprotein efflux. Horie, T; Oga, EF; Sekine, S, 2013)	0.83
" Three open-label phase 1 studies were conducted in healthy human participants to investigate potential pharmacokinetic (PK) and/or pharmacodynamic (PD) interactions between albiglutide and medications that may be used concomitantly."	( Effects of multiple doses of albiglutide on the pharmacokinetics, pharmacodynamics, and safety of digoxin, warfarin, or a low-dose oral contraceptive. Bush, M; Lewis, E; Scott, R; Watanalumlerd, P; Zhi, H, 2012)	0.6
" Therefore, a physiologically-based pharmacokinetic (PBPK) model for verapamil and its primary metabolite was developed and validated through the recovery of observed clinical plasma concentration data for both moieties and the reported interaction with midazolam, albeit a cytochrome P450 3A4-mediated DDI."	( Application of permeability-limited physiologically-based pharmacokinetic models: part II - prediction of P-glycoprotein mediated drug-drug interactions with digoxin. Barter, Z; Jamei, M; Neuhoff, S; Rostami-Hodjegan, A; Turner, DB; Yeo, KR, 2013)	0.59
" rifampicin) is a predictive pharmacokinetic model for digoxin itself."	( Application of permeability-limited physiologically-based pharmacokinetic models: part I-digoxin pharmacokinetics incorporating P-glycoprotein-mediated efflux. Barter, Z; Jamei, M; Neuhoff, S; Rostami-Hodjegan, A; Turner, DB; Yeo, KR, 2013)	0.86
" Pharmacokinetic parameters of digoxin and ticagrelor were evaluated following co-administration of ticagrelor 400 mg qd or placebo on days 1-16, and digoxin (0."	( A pharmacokinetic interaction study of ticagrelor and digoxin in healthy volunteers. Butler, K; Teng, R, 2013)	0.92
"To investigate the impact of the direct Factor Xa inhibitor darexaban administered in a modified-release formulation (darexaban-MR) on the pharmacokinetic (PK) profile of digoxin."	( Darexaban (YM150), an oral direct factor Xa inhibitor, has no effect on the pharmacokinetics of digoxin. Garcia-Hernandez, A; Groenendaal, D; Heeringa, M; Kadokura, T; Mol, R; Onkels, H; Verheggen, F, 2014)	0.81
" In this study, in vivo-based [I]/Ki values were used to predict the DDI risks of a P-gp substrate dabigatran etexilate (DABE) using physiologically based pharmacokinetic (PBPK) modelling."	( Physiologically based pharmacokinetic modelling and in vivo [I]/K(i) accurately predict P-glycoprotein-mediated drug-drug interactions with dabigatran etexilate. Hu, ZY; Zhao, Y, 2014)	0.4
"This approach accurately predicted the effects of five P-gp inhibitors on DABE pharmacokinetics (98-133% and 89-104% for the ratios of AUC and Cmax respectively)."	( Physiologically based pharmacokinetic modelling and in vivo [I]/K(i) accurately predict P-glycoprotein-mediated drug-drug interactions with dabigatran etexilate. Hu, ZY; Zhao, Y, 2014)	0.4
"The main goal of this study was to estimate the population pharmacokinetics of digoxin and to identify the nutritional status that explains pharmacokinetic variability in hospitalized Korean patients."	( A population pharmacokinetic analysis of the influence of nutritional status of digoxin in hospitalized Korean patients. Choi, SA; Lee, ES; Shin, WG; Yun, HY, 2014)	0.86
" The pharmacokinetics of digoxin were analyzed with a 1-compartment, open-label pharmacokinetic model by using a nonlinear mixed-effects modeling tool (NONMEM) and a multiple trough screening approach."	( A population pharmacokinetic analysis of the influence of nutritional status of digoxin in hospitalized Korean patients. Choi, SA; Lee, ES; Shin, WG; Yun, HY, 2014)	0.93
" The present study established important sources of variability in digoxin pharmacokinetics and highlighted the relationship between pharmacokinetic parameters and nutritional status in hospitalized Korean patients."	( A population pharmacokinetic analysis of the influence of nutritional status of digoxin in hospitalized Korean patients. Choi, SA; Lee, ES; Shin, WG; Yun, HY, 2014)	0.87
"Pradigastat, a novel diacylglycerol acyltransferase-1 inhibitor, was evaluated for both pharmacokinetic (PK) and pharmacodynamic (PD) drug-drug interactions when co-administered with digoxin or warfarin in healthy subjects."	( Pharmacokinetic and pharmacodynamic drug-drug interaction assessment between pradigastat and digoxin or warfarin. Chen, J; Danis, K; Lee, Z; Majumdar, T; Meyers, D; Neelakantham, S; Rebello, S; Sunkara, G; Yan, JH, 2014)	0.81
" Pharmacokinetic models of digitoxin and digoxin, containing a peripheral non-serum effect compartment, were used to analyze outcomes in a non-systematic literature review of five clinical studies, using the computed concentrations of digitoxin and digoxin in the effect compartment of these models in an analysis of their outcomes."	( The role of digitalis pharmacokinetics in converting atrial fibrillation and flutter to regular sinus rhythm. Jelliffe, RW, 2014)	0.67
"To obtain more information regarding the influence of various covariates on the disposition of digoxin in Chinese neonates and infants, routine clinical pharmacokinetic data were retrospectively collected from 131 hospitalized patients."	( Population pharmacokinetic analysis of digoxin in Chinese neonates and infants. Chen, Y; Gong, Y; Li, Q; Li, Z, 2014)	0.89
"To evaluate felodipine as a potential perpetrator of pharmacokinetic drug-drug interactions (PK-DDIs) involving cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp)."	( Evaluation of felodipine as a potential perpetrator of pharmacokinetic drug-drug interactions. Doogue, MP; Miners, JO; Polasek, TM; Rowland, A; Snyder, BD, 2014)	0.4
" Vandetanib + digoxin increased digoxin area under the concentration-time curve from zero to the last quantifiable concentration (AUC0-last) and Cmax by 23 and 29 %, respectively, versus digoxin alone, with only a 9 % decrease in CLR."	( Pharmacokinetic evaluations of the co-administrations of vandetanib and metformin, digoxin, midazolam, omeprazole or ranitidine. Johansson, S; Leese, PT; Li, Y; Lisbon, E; Martin, P; Mathews, D; Oliver, S; Read, J; Steinberg, M, 2014)	0.99
"Physiologically based pharmacokinetic modeling was applied to characterize the potential drug-drug interactions for ruxolitinib."	( Predicting drug-drug interactions involving multiple mechanisms using physiologically based pharmacokinetic modeling: a case study with ruxolitinib. Fraczkiewicz, G; Shi, JG; Williams, WV; Yeleswaram, S, 2015)	0.42
" The studies reported herein examined whether fostamatinib and R406 are inhibitors of P-glycoprotein (P-gp) in vitro and evaluated the effect of fostamatinib on the pharmacokinetic parameters of digoxin to understand drug-drug interaction (DDI) potential in the clinic."	( Effects of Fostamatinib on the Pharmacokinetics of Digoxin (a P-Glycoprotein Substrate): Results From in Vitro and Phase I Clinical Studies. Baluom, M; Brealey, C; Elsby, R; Gillen, M; Lau, D; Mant, T; Martin, P; Millson, D; Oliver, S, 2015)	0.86
" Median digoxin time of Cmax was earlier when digoxin was co-administered with fostamatinib (1."	( Effects of Fostamatinib on the Pharmacokinetics of Digoxin (a P-Glycoprotein Substrate): Results From in Vitro and Phase I Clinical Studies. Baluom, M; Brealey, C; Elsby, R; Gillen, M; Lau, D; Mant, T; Martin, P; Millson, D; Oliver, S, 2015)	1.1
" However, when administered as a cocktail the Cmax of furosemide was 19."	( Pharmacokinetic Evaluation of a Drug Transporter Cocktail Consisting of Digoxin, Furosemide, Metformin, and Rosuvastatin. Ebner, T; Gansser, D; Giessmann, T; Hohl, K; Ishiguro, N; Müller, F; Sharma, A; Stopfer, P; Taub, ME; Wein, M; Zimdahl-Gelling, H, 2016)	0.67
" Four phase 1 studies were conducted in healthy subjects to evaluate the potential for pharmacokinetic interactions between mirabegron and metformin, warfarin, digoxin, or a combination oral contraceptive (COC)."	( Pharmacokinetic Interactions Between Mirabegron and Metformin, Warfarin, Digoxin or Combined Oral Contraceptives. Groen-Wijnberg, M; Kerbusch, V; Krauwinkel, W; Meijer, J; Tretter, R; van Dijk, J; van Gelderen, M; Zhang, W, 2017)	0.88
" Pharmacokinetic parameters were determined by non-compartmental methods."	( Pharmacokinetic Interactions Between Mirabegron and Metformin, Warfarin, Digoxin or Combined Oral Contraceptives. Groen-Wijnberg, M; Kerbusch, V; Krauwinkel, W; Meijer, J; Tretter, R; van Dijk, J; van Gelderen, M; Zhang, W, 2017)	0.69
"No clinically significant pharmacokinetic or pharmacodynamic interactions were identified and no new safety issues observed with combined treatment with semaglutide."	( Effect of Semaglutide on the Pharmacokinetics of Metformin, Warfarin, Atorvastatin and Digoxin in Healthy Subjects. Anderson, TW; Derving Karsbøl, J; Golor, G; Hausner, H; Holst, AG; Jacobsen, JB; Wagner, FD, 2017)	0.68
"Data were analized: age, sex, diagnosis, number of serum digoxin concentration determinations, date and origin of the request for monitoring, analytical result and pharmacokinetic assessment are collected."	( Pharmacokinetic monitoring of chronic treatment with digoxin from Primary Health Care. García-Iranzo, EM; García-Monsalve, A; Matoses-Chirivella, C; Murcia-López, AC; Navarro-Ruiz, A; Rodríguez-Lucena, FJ, 2017)	0.95
"A small proportion of patients undergoing chronic treatment with digoxin are under pharmacokinetic monitoring and a reduction in complications derived from inappropriate CSD compared to those not under pharmacokinetic follow-up is observed."	( Pharmacokinetic monitoring of chronic treatment with digoxin from Primary Health Care. García-Iranzo, EM; García-Monsalve, A; Matoses-Chirivella, C; Murcia-López, AC; Navarro-Ruiz, A; Rodríguez-Lucena, FJ, 2017)	0.94
" Blood samples for the pharmacokinetic assessments of digoxin were collected up to 8 hours after each dose."	( Effect of green tea catechins on the pharmacokinetics of digoxin in humans. Choi, DH; Kim, MG; Kim, TE; Kwon, KJ; Lee, J; Park, JE; Shin, KH; Yun, YM, 2018)	0.97
" Physiologically based pharmacokinetic (PBPK) modelling creates clinical simulations which are closely related to physiological and pharmacokinetic behaviour."	( Physiologically based pharmacokinetic modelling of acute digoxin toxicity and the effect of digoxin-specific antibody fragments. Bracken, LM; Buckley, NA; Chan, BSH, 2019)	0.76
"A randomized, controlled, single- and multiple-dose study was conducted to evaluate the pharmacokinetic profiles of orally and intravenously administered digoxin."	( Effect of purple grape juice on the pharmacokinetics of digoxin: Results of a food-drug interaction study . Ju, Y; Qiu, W; Song, X; Zhao, H, 2019)	0.96
"Physiologically-based pharmacokinetic (PBPK) modeling is a powerful tool to quantitatively describe drug disposition profiles in vivo, thereby providing an alternative to predict drug-drug interactions (DDIs) that have not been tested clinically."	( Physiologically-Based Pharmacokinetic Modeling Approach to Predict Rifampin-Mediated Intestinal P-Glycoprotein Induction. Costales, C; Eatemadpour, S; Kimoto, E; Lazzaro, S; Varma, MV; Yamazaki, S, 2019)	0.51
"P-glycoprotein (P-gp/ABCB1) is an ATP-binding cassette drug efflux transporter expressed in a variety of tissues that affects the pharmacokinetic disposition of many drugs."	( Estradiol regulation of P-glycoprotein expression in mouse kidney and human tubular epithelial cells, implication for renal clearance of drugs. Akamine, T; Kanado, Y; Koyanagi, S; Kusunose, N; Matsunaga, N; Ohdo, S; Omata, Y; Tsurudome, Y; Yasukochi, S, 2019)	0.51
" We use this case to demonstrate the potential role of physiologically based pharmacokinetic modeling in assisting therapeutic decision making."	( Utility of Physiologically Based Pharmacokinetic Modeling in Point-of-Care Decisions: An Example Using Digoxin Dosing in Continuous Venovenous Hemodiafiltration. Chaturvedula, A; Hirani, R; Kabani, K; Palasik, B; Srinivasan, M; Tsiu, M, 2020)	0.77
" All paediatric population pharmacokinetic studies of digoxin that utilized the nonlinear mixed-effect modelling approach were incorporated in this review, and data were synthesized descriptively."	( A systematic review of population pharmacokinetic analyses of digoxin in the paediatric population. Abdel Jalil, MH; Abdullah, N; Abu-Hammour, K; Alsous, MM; Saleh, M, 2020)	1.05
"To develop a novel intestinal drug absorption system using intestinal epithelial cells derived from human induced pluripotent stem (iPS) cells, the cells must possess sufficient pharmacokinetic functions."	( Pharmacokinetic functions of human induced pluripotent stem cell-derived small intestinal epithelial cells. Imakura, Y; Iwao, T; Kabeya, T; Matsunaga, T; Mima, S; Miyashita, T; Ogura, I; Yamada, T; Yasujima, T; Yuasa, H, 2020)	0.56
"This study aimed to utilize a population pharmacokinetic method to obtain information about the influence of covariates on the in vivo behavior of digoxin in patients with cardiac insufficiency."	( Impact of SLCO4C1 Genotypes, Creatinine, and Spironolactone on Digoxin Population Pharmacokinetic Variables in Patients With Cardiac Insufficiency. Du, P; Jia, A; Li, X; Li, Y; Ma, Y; Wang, A, 2020)	1
" The first-order absorption one-compartment model was used to develop a population pharmacokinetic model from a nonlinear mixed effects modeling approach."	( Impact of SLCO4C1 Genotypes, Creatinine, and Spironolactone on Digoxin Population Pharmacokinetic Variables in Patients With Cardiac Insufficiency. Du, P; Jia, A; Li, X; Li, Y; Ma, Y; Wang, A, 2020)	0.8
" A literature search was conducted using the ISI Web of Science, Science Direct, PubMed, and SCOPUS databases to identify digoxin population pharmacokinetic studies of adults that utilized the nonlinear mixed-effect modeling approach."	( Population Pharmacokinetic Studies of Digoxin in Adult Patients: A Systematic Review. Abdel Jalil, M; Abdullah, N; Abu-Hammour, K; Alsous, M, 2021)	1.1
"This is the first study to report digoxin pharmacokinetic changes caused by hepatic P-gp upregulation in NAFLD."	( Changes in digoxin pharmacokinetics associated with hepatic P-glycoprotein upregulation in rats with non-alcoholic fatty liver disease. Jeong, HJ; Kang, HE; Lee, SH, 2021)	1.29
"The pharmacodynamic effects of digoxin are susceptible to multiple factors, most notably, heart uptake of the digoxin dose and its concentration in the serum."	( Pharmacokinetics Parameters of Diagoxin among Saudi Patients in Qassim Region, Saudi Arabia. Allihimy, AS; Almadhi, J; Almeman, AA; Alnassar, NA, 2021)	0.91
"In this study, we aimed to develop a simple algorithm based on subsets of clinically relevant information, which will help to personalize digoxin based on pharmacokinetic (PK) approach which can help in marketing the appropriate utilization of this medication."	( Pharmacokinetics Parameters of Diagoxin among Saudi Patients in Qassim Region, Saudi Arabia. Allihimy, AS; Almadhi, J; Almeman, AA; Alnassar, NA, 2021)	0.82
" All pharmacokinetic parameters were added according to the C-peaks and C-troughs."	( Pharmacokinetics Parameters of Diagoxin among Saudi Patients in Qassim Region, Saudi Arabia. Allihimy, AS; Almadhi, J; Almeman, AA; Alnassar, NA, 2021)	0.62
"The aim of this work is the development of a mechanistic physiologically-based pharmacokinetic (PBPK) model using in vitro to in vivo extrapolation to conduct a drug-drug interaction (DDI) assessment of treosulfan against two cytochrome p450 (CYP) isoenzymes and P-glycoprotein (P-gp) substrates."	( Evaluation of the drug-drug interaction potential of treosulfan using a physiologically-based pharmacokinetic modelling approach. Balazki, P; Baumgart, J; Beelen, DW; Böhm, S; Hemmelmann, C; Hilger, RA; Martins, FS; Ring, A; Schaller, S, 2022)	0.72
" However, considering the comprehensive treosulfan-based conditioning treatment schedule and the respective pharmacokinetic properties of the concomitantly used drugs (eg, half-life), the potential for interaction on all evaluated mechanisms would be low (AUCR < 1."	( Evaluation of the drug-drug interaction potential of treosulfan using a physiologically-based pharmacokinetic modelling approach. Balazki, P; Baumgart, J; Beelen, DW; Böhm, S; Hemmelmann, C; Hilger, RA; Martins, FS; Ring, A; Schaller, S, 2022)	0.72
" In conclusion, OM coadministered with digoxin or amiodarone did not result in any clinically relevant pharmacokinetic drug-drug interactions."	( Pharmacokinetic Drug-Drug Interaction Study of Omecamtiv Mecarbil With Amiodarone and Digoxin in Healthy Subjects. Abbasi, S; Dutta, S; Flach, S; Hsu, CP; Hutton, S; Jafarinasabian, P; Lee, E; Sohn, W; Trivedi, A; Zhang, H, 2022)	1.21
"As one of the key components in model-informed drug discovery and development, physiologically-based pharmacokinetic (PBPK) modeling linked with in vitro-to-in vivo extrapolation (IVIVE) is widely applied to quantitatively predict drug-drug interactions (DDIs) on drug-metabolizing enzymes and transporters."	( Physiologically-based pharmacokinetic modeling to evaluate in vitro-to-in vivo extrapolation for intestinal P-glycoprotein inhibition. De Zwart, L; Evers, R; Yamazaki, S, 2022)	0.72
" The presence of steady-state letermovir reduced digoxin area under the plasma concentration-time curve from administration until last quantifiable measurement by 12% and maximum plasma concentration by 22% compared with digoxin alone; digoxin half-life and elimination rate remained similar in both conditions."	( The Effect of Oral Letermovir Administration on the Pharmacokinetics of a Single Oral Dose of P-Glycoprotein Substrate Digoxin in Healthy Volunteers. Erb-Zohar, K; Kropeit, D; McCormick, D; Rübsamen-Schaeff, H; Scheuenpflug, J; Stobernack, HP; Theis, JGW; Zimmermann, H, 2022)	1.18
" In the present study, we developed a human transplacental pharmacokinetic model of digoxin using previously reported ex vivo human placental perfusion data."	( Transplacental Pharmacokinetic Model of Digoxin Based on Ex Vivo Human Placental Perfusion Study. Chiba, K; Kurosawa, K; Nishimura, T; Noguchi, S; Tomi, M, 2022)	1.21
" This study aimed to establish a physiologically based pharmacokinetic (PBPK) model of rifampicin to predict the P-gp-mediated drug-drug interactions (DDIs) and assess the DDI impact in the intestine, liver, and kidney."	( Robust physiologically based pharmacokinetic model of rifampicin for predicting drug-drug interactions via P-glycoprotein induction and inhibition in the intestine, liver, and kidney. Asaumi, R; Nunoya, KI; Sugiyama, Y; Taskar, KS; Yamaura, Y, 2022)	0.72
" NONMEM was used for pharmacokinetic analysis of digoxin  blood levels, being mostly described by a one-compartment model."	( Population pharmacokinetics of digoxin in elderly patients: A systematic review. Barcia-Hernández, E; García-Díaz, B; Salcedo-Mingoarranz, ÁL, 2022)	1.26
" Pharmacokinetic characteristics of probe drugs were subsequently assessed in a Phase I, open-label, single-sequence crossover study in healthy male participants."	( Pharmacokinetic-Interactions of BI 425809, a Novel Glycine Transporter 1 Inhibitor, With Cytochrome P450 and P-Glycoprotein Substrates: Findings From In Vitro Analyses and an Open-Label, Single-Sequence Phase I Study. Chan, T; Desch, M; Hohl, K; Ishiguro, N; Keller, S; Liesenfeld, KH; Müller, F; Schlecker, C; Wind, S; Wunderlich, G, )	0.13
" With BI 425809, area under the plasma concentration curve from administration to the last measurement (AUC 0-tz ) and maximum plasma concentration ( Cmax ) for midazolam were lower than when administered alone."	( Pharmacokinetic-Interactions of BI 425809, a Novel Glycine Transporter 1 Inhibitor, With Cytochrome P450 and P-Glycoprotein Substrates: Findings From In Vitro Analyses and an Open-Label, Single-Sequence Phase I Study. Chan, T; Desch, M; Hohl, K; Ishiguro, N; Keller, S; Liesenfeld, KH; Müller, F; Schlecker, C; Wind, S; Wunderlich, G, )	0.13
" Based on prescription information and literature, we selected the agents that were moderate/strong inducers or inhibitors of pharmacokinetic human molecular determinants of pharmacological interest (enzymes, drug transporters) highlighting on clinically meaningful interactions (i."	( Oral anticancer agents as generators of relevant pharmacokinetic interactions. Levêque, D; Machkouri, C, 2023)	0.91
"5 for digoxin), 24 oral anticancer agents commercialised in the European Union and the United States are susceptible to generate clinically meaningful pharmacokinetic interactions with comedications."	( Oral anticancer agents as generators of relevant pharmacokinetic interactions. Levêque, D; Machkouri, C, 2023)	1.39
" These potential pharmacokinetic interactions are likely to occur in the ambulatory setting in a polymedicated and aged population, needing to reinforce the vigilance of community pharmacists and health care providers (particularly in thoracic oncology and genitourinary cancer) with these sometimes rarely prescribed agents."	( Oral anticancer agents as generators of relevant pharmacokinetic interactions. Levêque, D; Machkouri, C, 2023)	0.91

Compound-Compound Interactions

Intravenous amiodarone alone or in combination with digoxin was found to be safe and effective in controlling refractory and life-threatening SVT in neonates and small infants. There was no significant difference between the bio-availability of beta-acetyldigoxine alone and that of the combination with Alucol.

Excerpt	Reference	Relevance
" These drugs may interact pharmacokinetically or pharmacodynamically, and most drug interactions are therapeutically useful."	( [Drug interactions in cardiovascular therapy]. Koch-Weser, J, 1976)	0.26
" The binding of digitoxin and cardioactive metabolites to serum proteins was studied using equilibrium dialysis (an in vitro chemical assay) alone and in combination with a modified 86Rb method."	( Studies on digitalis. V. The influence of impaired renal function, hemodialysis, and drug interaction on serum protein binding of digitoxin and digoxin. Storstein, L, 1976)	0.46
" There was no significant difference between the bio-availability of beta-acetyldigoxine alone and that of the combination with Alucol."	( The bio-availability of beta-acetyldigoxine alone and combined with aluminum hydroxide and magnesium hydroxide (Alucol). Bonelli, J; Hitzenberger, G; Hruby, K; Kaik, G; Magometschnigg, D, 1977)	0.76
" In 28 patients, ethacizine was administered in combination with glutamic acid and in 23 with digoxin."	( [The characteristics of the action of ethacizine and its combination with digoxin and glutamic acid on the hemodynamic indices and myocardial contractile capacity in patients with a heart rhythm disorder]. Nikolaeva, SA; Poliakova, LA; Zapevina, VV, 1990)	0.73
"Rifampin, a potent inducer of the hepatic microsomal system, has been shown to cause clinically important interactions when combined with other drugs, including oral anticoagulants, oral contraceptives, digitoxin, methadone hydrochloride, sulfonylureas, and barbiturates."	( Update on rifampin drug interactions. Baciewicz, AM; Bekemeyer, WB; Self, TH, 1987)	0.27
"In the clinical management of heart disease, calcium channel blockers are generally prescribed in combination with one or more anti-angina, antiarrhythmic, or antihypertensive agents."	( Calcium antagonists--adverse drug interactions. Ebner, FX; Neufeld, HN; Reicher-Reiss, H, 1987)	0.27
"We evaluated the efficacy and the safety of medium-(240 mn/day) and high-dose (360 mg/day) diltiazem alone and in combination with digoxin when used for control of heart rate in 12 patients with chronic atrial fibrillation."	( Efficacy and safety of medium- and high-dose diltiazem alone and in combination with digoxin for control of heart rate at rest and during exercise in patients with chronic atrial fibrillation. Cohen, J; Elkayam, U; Harrison, E; Mitani, G; Rahimtoola, SH; Roth, A, 1986)	0.7
" Furthermore, amiodarone may interact with beta-blocking agents and some of the calcium antagonists to produce symptomatic sinus bradycardia and sinus arrest, especially in a latent or overt sick sinus syndrome."	( Drug interactions with amiodarone. Marcus, FI, 1983)	0.27
" These effects, combined with the common use of cimetidine in clinical practice, make the risk of adverse drug interactions a relatively frequent risk in the clinical setting."	( Drug interactions involving cimetidine--mechanisms, documentation, implications. Greene, W, 1984)	0.27
" Fibrates should not be combined with HMG-CoA reductase inhibitors because of the increased risk of myopathy."	( Serious drug interactions. Aronson, J, 1993)	0.29
" Different mechanisms have to be considered as causes for potential drug-drug interactions."	( Lack of pantoprazole drug interactions in man. Bliesath, H; Hartmann, M; Huber, R; Radtke, HW; Steinijans, VW; Wurst, W; Zech, K, 1994)	0.29
"2 years, 1,594 (31%) had at least one interacting drug combination according to the Swedish National Formulary."	( Potential drug--drug interactions in 5,125 mostly elderly out-patients in Gothenburg, Sweden. Bergendal, L; Friberg, A; Schaffrath, A, 1995)	0.29
"2 mg daily), or nefazodone combined with digoxin during three 8-day treatment periods, with a single dose on the ninth day."	( Assessment of pharmacokinetic and pharmacodynamic drug interactions between nefazodone and digoxin in healthy male volunteers. Barbhaiya, RH; Dockens, RC; Greene, DS, 1996)	0.78
" Candesartan cilexetil was well tolerated both alone and in combination with the other agents."	( Pharmacokinetic drug interaction studies with candesartan cilexetil. Högemann, A; Jonkman, JH; Lins, R; Sennewald, R; van Heiningen, PN; van Lier, JJ, 1997)	0.3
"5 mg digoxin administered alone or in combination with macrogol 4000, 20 g day-1 during 8 days."	( Pharmacokinetic and pharmacodynamic drug interactions between digoxin and macrogol 4000, a laxative polymer, in healthy volunteers. Funck-Brentano, C; Jaillon, P; Poirier, JM; Radembino, N; Ragueneau, I; Sao, AB, 1999)	1.06
" In some cases of atrial fibrillation digoxin is used in combination with verapamil."	( P-glycoprotein system as a determinant of drug interactions: the case of digoxin-verapamil. Beijnen, JH; Koks, CH; Schellens, JH; Verschraagen, M, 1999)	0.81
" There was no clinically relevant change in the effect of digoxin on vital signs or electrocardiographic parameters when administered with single- or multiple-dose valspodar compared with administration alone in volunteers with healthy cardiovascular systems."	( Longitudinal assessment of a P-glycoprotein-mediated drug interaction of valspodar on digoxin. Gerbeau, C; Guerret, M; Kovarik, JM; Rigaudy, L; Rost, KL, 1999)	0.77
" No direct drug-drug interactions were found in these studies, suggesting that repaglinide may be coprescribed with cimetidine, digoxin, or theophylline at the dosage used for monotherapy."	( Drug interaction studies with repaglinide: repaglinide on digoxin or theophylline pharmacokinetics and cimetidine on repaglinide pharmacokinetics. Hatorp, V; Thomsen, MS, 2000)	0.76
"The drug-drug interactions discussed in this article have either documented or suspected clinical relevance for patients with cardiovascular disease and the clinician involved in the care of these patients."	( Cardiovascular drug-drug interactions. Anderson, JR; Nawarskas, JJ, 2001)	0.31
"The aim of this work is to identify the medicines which interact with the herbal remedy St John's wort (SJW), and the mechanisms responsible."	( St John's wort (Hypericum perforatum): drug interactions and clinical outcomes. Arlett, P; Bergquist, C; Gerden, B; Henderson, L; Yue, QY, 2002)	0.31
"Many hospital admissions of elderly patients for drug toxicity occur after administration of a drug known to cause drug-drug interactions."	( Drug-drug interactions among elderly patients hospitalized for drug toxicity. Juurlink, DN; Kopp, A; Laupacis, A; Mamdani, M; Redelmeier, DA, 2003)	0.32
"MDC of HF remains cost-beneficial when combined with optimal, medical care."	( Is multidisciplinary care of heart failure cost-beneficial when combined with optimal medical care? Barry, M; Cahill, J; Ledwidge, M; Maurer, B; McDonald, K; Ryan, E; Ryder, M; Timmons, L; Travers, B, 2003)	0.32
" For drugs with narrow therapeutic windows, such as digoxin, an understanding of the potential mechanisms by which drugs might interact is essential to clinical practice."	( From bench to bedside: utilization of an in vitro model to predict potential drug-drug interactions in the kidney: the digoxin-mifepristone example. Ito, S; Koren, G; Woodland, C, 2003)	0.78
" The HPLC-separation used a 10 x 2 mm LiChrospher RP-18 5 microm guard column in combination with a 125 x 2 mm main column of the same material and a gradient containing methanol, caesium ions and formic acid."	( Determination of the cardiac glycosides digoxin and digitoxin by liquid chromatography combined with isotope-dilution mass spectrometry (LC-IDMS)--a candidate reference measurement procedure. Kaiser, P; Kramer, U; Kress, M; Meissner, D; Reinauer, H; Wood, WG, 2003)	0.59
" However, this component may take part in vivo and contribute to drug-drug interactions involving P-gp."	( pH-dependent bidirectional transport of weakly basic drugs across Caco-2 monolayers: implications for drug-drug interactions. Artursson, P; Neuhoff, S; Ungell, AL; Zamora, I, 2003)	0.32
" We conclude that the interplay of transporters and enzymes must be considered in defining the intrinsic metabolic clearance of the liver and in evaluating potential drug-drug interactions."	( Hepatic microsome studies are insufficient to characterize in vivo hepatic metabolic clearance and metabolic drug-drug interactions: studies of digoxin metabolism in primary rat hepatocytes versus microsomes. Benet, LZ; Lam, JL, 2004)	0.52
"To estimate the rate of potential drug-drug interactions in outpatients of a typical Thai university hospital, and to identify risk factors for such interactions in Thai patients."	( Pharmacoepidemiologic study of potential drug interactions in outpatients of a university hospital in Thailand. Chongsuvivatwong, V; Janchawee, B; Owatranporn, T; Wongpoowarak, W, 2005)	0.33
" Since DDIs are associated with adverse reactions, we performed a cross-sectional study to assess the prevalence of potentially critical drug-drug and drug-statin interactions in an outpatient adult population with dyslipidaemia."	( Prevalence of potentially severe drug-drug interactions in ambulatory patients with dyslipidaemia receiving HMG-CoA reductase inhibitor therapy. Hess, L; Krähenbühl, S; Krähenbühl-Melcher, A; Rätz Bravo, AE; Schlienger, RG; Tchambaz, L, 2005)	0.33
"Regulatory interest is increasing for drug transporters generally and P-glycoprotein (Pgp) in particular, primarily in the area of drug-drug interactions."	( Development, validation and utility of an in vitro technique for assessment of potential clinical drug-drug interactions involving P-glycoprotein. Keogh, JP; Kunta, JR, 2006)	0.33
"The authors studied a potential drug-drug interaction via findings from in vitro and in vivo studies, to assess whether the in vitro system was predictive of in vivo clinical pharmacokinetic outcomes."	( Predictive power of an in vitro system to assess drug interactions of an antimuscarinic medication: a comparison of in vitro and in vivo drug-drug interaction studies of trospium chloride with digoxin. Fox, L; Harnett, M; Lasseter, K; Profy, A; Sabounjian, L; Sandage, B; Shipley, J, 2006)	0.52
"The clinical pharmacokinetics and in vitro inhibition of digoxin were examined to predict the P-glycoprotein (P-gp) component of drug-drug interactions."	( Drug-drug interactions mediated through P-glycoprotein: clinical relevance and in vitro-in vivo correlation using digoxin as a probe drug. Cook, JA; Fenner, KS; Kempshall, S; Lee, CA; Smith, DA; Troutman, MD; Ware, JA, 2009)	0.81
" Selected cardiac glycosides were tested in combination with four clinically relevant cytotoxic drugs (5-fluorouracil, oxaliplatin, cisplatin, irinotecan)."	( Cytotoxic effects of cardiac glycosides in colon cancer cells, alone and in combination with standard chemotherapeutic drugs. Bohlin, L; Felth, J; Fryknäs, M; Gullbo, J; Lindskog, M; Rickardson, L; Rosén, J; Wickström, M, 2009)	0.35
"The purpose of this study was to report the efficacy of intravenous amiodarone alone or in combination with digoxin in neonates and small infants with life-threatening supraventricular tachyarrhythmia (SVT)."	( Intravenous amiodarone used alone or in combination with digoxin for life-threatening supraventricular tachyarrhythmia in neonates and small infants. Aslan, Y; Celiker, A; Dilber, B; Dilber, E; Gedik, Y; Mutlu, M, 2010)	0.82
"We retrospectively analyzed 9 neonates and small infants with life-threatening or resistant SVT who were treated with intravenous amiodarone alone or in combination with digoxin."	( Intravenous amiodarone used alone or in combination with digoxin for life-threatening supraventricular tachyarrhythmia in neonates and small infants. Aslan, Y; Celiker, A; Dilber, B; Dilber, E; Gedik, Y; Mutlu, M, 2010)	0.8
" Amiodarone alone or in combination with digoxin effectively controlled reentrant SVT in all patients."	( Intravenous amiodarone used alone or in combination with digoxin for life-threatening supraventricular tachyarrhythmia in neonates and small infants. Aslan, Y; Celiker, A; Dilber, B; Dilber, E; Gedik, Y; Mutlu, M, 2010)	0.87
"Intravenous amiodarone alone or in combination with digoxin was found to be safe and effective in controlling refractory and life-threatening SVT in neonates and small infants."	( Intravenous amiodarone used alone or in combination with digoxin for life-threatening supraventricular tachyarrhythmia in neonates and small infants. Aslan, Y; Celiker, A; Dilber, B; Dilber, E; Gedik, Y; Mutlu, M, 2010)	0.86
" Drug-drug interactions were investigated when nebivolol was coadministered to subjects classified as poor CYP2D6 metabolizers and extensive CYP2D6 metabolizers who were receiving other drugs commonly administered to patients with hypertension or compounds metabolized by cytochrome P450 (CYP) 2D6."	( Effects of commonly administered agents and genetics on nebivolol pharmacokinetics: drug-drug interaction studies. Gorski, JC; Lindamood, C; Ortiz, S; Rackley, R; Shaw, A, 2011)	0.37
" Inhibition or induction of P-gp can cause drug-drug interactions and thus influence the effects of P-gp substrate drugs."	( 20(S)-ginsenoside Rh2 noncompetitively inhibits P-glycoprotein in vitro and in vivo: a case for herb-drug interactions. Ai, H; Gu, Y; Hao, G; Li, Y; Peng, Y; Sun, J; Wang, G; Wu, X; Zhang, J; Zhang, X; Zheng, Y; Zhou, F, 2010)	0.36
" In this study, the drug-drug interaction (DDI) potential of N-(1-{(3R)-3-(3,5-difluorophenyl)-3-[4-methanesulfonylphenyl]propyl}piperidin-4-yl)-N-ethyl-2-[4-methanesulfonylphenyl]acetamide (AZD5672) was assessed accordingly, and a subsequent clinical digoxin interaction study was performed."	( The utility of in vitro data in making accurate predictions of human P-glycoprotein-mediated drug-drug interactions: a case study for AZD5672. Butters, C; Elsby, R; Gillen, M; Imisson, G; Sharma, P; Smith, V; Surry, DD, 2011)	0.55
" These results suggest modifications to drug-drug interaction (DDI) trial designs."	( Rifampin's acute inhibitory and chronic inductive drug interactions: experimental and model-based approaches to drug-drug interaction trial design. Cai, X; Chu, X; Ding, Y; Evers, R; Gibson, C; Reitman, ML; Roupe, K; Stoch, A; Stone, JA; Venkatasubramanian, R; Wagner, JA; Witter, R; Yabut, J; Zajic, S, 2011)	0.37
"The decision tree to determine whether the P-glycoprotein (P-gp)/multidrug resistance protein 1 (MDR1)-mediated drug-drug interaction (DDI) study is recommended has been proposed by the International Transporter Consortium."	( Establishment of in vitro P-glycoprotein inhibition assay and its exclusion criteria to assess the risk of drug-drug interaction at the drug discovery stage. Amano, N; Hirabayashi, H; Matsumoto, S; Moriwaki, T; Niwa, S; Sugimoto, H; Tachibana, M, 2011)	0.37
"As part of a larger clinical drug-drug interaction (DDI) study aimed at in vitro to in vivo prediction of HIV protease inhibitor metabolic and transporter-based DDIs, we measured the inductive (staggered administration) and inductive plus inhibitory (simultaneously administered) effect of multiple dose ritonavir (RTV), nelfinavir (NFV), or rifampin (RIF) on the pharmacokinetics of the P-glycoprotein probe, digoxin (DIG), when administered simultaneously or staggered with the protease inhibitors or RIF."	( Complex drug interactions of the HIV protease inhibitors 3: effect of simultaneous or staggered dosing of digoxin and ritonavir, nelfinavir, rifampin, or bupropion. Collier, AC; Kharasch, ED; Kirby, BJ; Thummel, KE; Unadkat, JD; Whittington, D, 2012)	0.76
"The hepatic organic anion transporting polypeptides (OATPs) influence the pharmacokinetics of several drug classes and are involved in many clinical drug-drug interactions."	( Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. Artursson, P; Haglund, U; Karlgren, M; Kimoto, E; Lai, Y; Norinder, U; Vildhede, A; Wisniewski, JR, 2012)	0.38
" We used a panel of stably and transiently transfected cell lines to elucidate the carrier-mediated transport processes that are involved in linagliptin disposition in vivo and to assess the potential for drug-drug interactions (DDIs)."	( Evaluation and prediction of potential drug-drug interactions of linagliptin using in vitro cell culture methods. Ebner, T; Ishiguro, N; Kishimoto, W; Schaefer, O; Shimizu, H, 2013)	0.39
"The goal of this study was to investigate potential drug-drug interactions between empagliflozin and verapamil, ramipril, and digoxin in healthy volunteers."	( Lack of clinically relevant drug-drug interaction between empagliflozin, a sodium glucose cotransporter 2 inhibitor, and verapamil, ramipril, or digoxin in healthy volunteers. Broedl, UC; Macha, S; Pinnetti, S; Rose, P; Schoene, K; Sennewald, R; Woerle, HJ, 2013)	0.8
"The potential drug-drug interactions were evaluated in 3 separate trials."	( Lack of clinically relevant drug-drug interaction between empagliflozin, a sodium glucose cotransporter 2 inhibitor, and verapamil, ramipril, or digoxin in healthy volunteers. Broedl, UC; Macha, S; Pinnetti, S; Rose, P; Schoene, K; Sennewald, R; Woerle, HJ, 2013)	0.59
" The impact of these findings on drug-drug interaction risk assessment is discussed in the companion article (Ellens et al."	( Variability in P-glycoprotein inhibitory potency (IC₅₀) using various in vitro experimental systems: implications for universal digoxin drug-drug interaction risk assessment decision criteria. Balimane, P; Bednarczyk, D; Bentz, J; Brännström, M; Chu, X; Coleman, J; Ellens, H; Funk, C; Guo, A; Hanna, I; Herédi-Szabó, K; Hillgren, K; Hollnack-Pusch, E; Jamei, M; Lee, C; Li, L; Lin, X; Mason, AK; Neuhoff, S; O'Connor, MP; Pak, YA; Palm, J; Patel, A; Perloff, ES; Plise, E; Podila, L; Rajaraman, G; Reyner, E; Salphati, L; Sands, E; Taub, ME; Taur, JS; Weitz, D; Wortelboer, HM; Xia, CQ; Xiao, G; Yabut, J; Yamagata, T; Zhang, L, 2013)	0.6
"In the 2012 Food and Drug Administration (FDA) draft guidance on drug-drug interactions (DDIs), a new molecular entity that inhibits P-glycoprotein (P-gp) may need a clinical DDI study with a P-gp substrate such as digoxin when the maximum concentration of inhibitor at steady state divided by IC₅₀ ([I₁]/IC₅₀) is ≥0."	( Application of receiver operating characteristic analysis to refine the prediction of potential digoxin drug interactions. Balimane, P; Bednarczyk, D; Bentz, J; Chu, X; Chung, SP; Coleman, J; Deng, S; Ellens, H; Forsgard, M; Funk, C; Guo, A; Hanna, I; Herédi-Szabó, K; Hillgren, KM; Jamei, M; Lee, CA; Li, L; Neuhoff, S; O'Connor, M; Pak, AY; Palm, J; Perloff, ES; Ragueneau-Majlessi, I; Rajaraman, G; Salphati, L; Taub, ME; Taur, JS; Weitz, D; Wortelboer, HM; Xia, CQ; Xiao, G; Yamagata, T; Zhang, L, 2013)	0.79
"Digoxin is the recommended substrate for assessment of P-glycoprotein (P-gp)-mediated drug-drug interactions (DDIs) in vivo."	( Application of permeability-limited physiologically-based pharmacokinetic models: part II - prediction of P-glycoprotein mediated drug-drug interactions with digoxin. Barter, Z; Jamei, M; Neuhoff, S; Rostami-Hodjegan, A; Turner, DB; Yeo, KR, 2013)	2.03
" Dabigatran etexilate was proposed as an in vivo probe substrate for intestinal P-gp inhibition in a recent guidance on drug-drug interactions (DDI) from the European Medicines Agency (EMA) and the Food and Drug Administration (FDA)."	( In vitro predictability of drug-drug interaction likelihood of P-glycoprotein-mediated efflux of dabigatran etexilate based on [I]2/IC50 threshold. Ebner, T; Ishiguro, N; Kishimoto, W; Ludwig-Schwellinger, E; Schaefer, O, 2014)	0.4
"In vitro inhibitory potency (Ki )-based predictions of P-glycoprotein (P-gp)-mediated drug-drug interactions (DDIs) are hampered by the substantial variability in inhibitory potency."	( Physiologically based pharmacokinetic modelling and in vivo [I]/K(i) accurately predict P-glycoprotein-mediated drug-drug interactions with dabigatran etexilate. Hu, ZY; Zhao, Y, 2014)	0.4
" Drug-drug interactions involving voclosporin and CYP3A substrates are not expected."	( Cytochrome P450 3A and P-glycoprotein drug-drug interactions with voclosporin. Aspeslet, LJ; Foster, RT; Freitag, DG; Huizinga, RB; Larouche, R; Ling, SY; Mayo, PR, 2014)	0.4
"Modulation of drug transporters via herbal medicines which have been widely used in combination with conventional prescription drugs may result in herb-drug interactions in clinical practice."	( Inhibitory effects of herbal constituents on P-glycoprotein in vitro and in vivo: herb-drug interactions mediated via P-gp. Hu, J; Li, X; Li, Y; Liu, Z; Sheng, L; Wang, B; Yang, S, 2014)	0.4
"Pradigastat, a novel diacylglycerol acyltransferase-1 inhibitor, was evaluated for both pharmacokinetic (PK) and pharmacodynamic (PD) drug-drug interactions when co-administered with digoxin or warfarin in healthy subjects."	( Pharmacokinetic and pharmacodynamic drug-drug interaction assessment between pradigastat and digoxin or warfarin. Chen, J; Danis, K; Lee, Z; Majumdar, T; Meyers, D; Neelakantham, S; Rebello, S; Sunkara, G; Yan, JH, 2014)	0.81
" Therefore, the potential pharmacokinetic drug-drug interactions between sucroferric oxyhydroxide and selected drugs commonly taken by dialysis patients were investigated."	( Drug-drug interactions between sucroferric oxyhydroxide and losartan, furosemide, omeprazole, digoxin and warfarin in healthy subjects. Chong, E; Kalia, V; Willsie, S; Winkle, P, 2014)	0.62
"Systemic exposure based on AUC0-∞ for all drugs, and AUC0-24 for all drugs except omeprazole (for which AUC 0-8 h was measured), was unaffected to a clinically significant extent by the presence of sucroferric oxyhydroxide, irrespective of whether sucroferric oxyhydroxide was administered with the drug or 2 h earlier."	( Drug-drug interactions between sucroferric oxyhydroxide and losartan, furosemide, omeprazole, digoxin and warfarin in healthy subjects. Chong, E; Kalia, V; Willsie, S; Winkle, P, 2014)	0.62
"There is a low risk of drug-drug interactions between sucroferric oxyhydroxide and losartan, furosemide, digoxin and warfarin."	( Drug-drug interactions between sucroferric oxyhydroxide and losartan, furosemide, omeprazole, digoxin and warfarin in healthy subjects. Chong, E; Kalia, V; Willsie, S; Winkle, P, 2014)	0.84
"To evaluate felodipine as a potential perpetrator of pharmacokinetic drug-drug interactions (PK-DDIs) involving cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp)."	( Evaluation of felodipine as a potential perpetrator of pharmacokinetic drug-drug interactions. Doogue, MP; Miners, JO; Polasek, TM; Rowland, A; Snyder, BD, 2014)	0.4
" Based on these results, a series of clinical drug-drug interaction (DDI) studies were conducted to evaluate the effect of ivacaftor on sensitive substrates of CYP2C8 (rosiglitazone), CYP3A (midazolam), CYP2D6 (desipramine), and P-gp (digoxin)."	( Clinical drug-drug interaction assessment of ivacaftor as a potential inhibitor of cytochrome P450 and P-glycoprotein. Chavan, AB; Dubey, N; Gilmartin, GS; Higgins, M; Li, C; Luo, X; Mahnke, L; Robertson, SM, 2015)	0.6
"The "P-glycoprotein" IC50 working group reported an 18- to 796-fold interlaboratory range in digoxin transport IC50 (inhibitor concentration achieving 50% of maximal inhibition), raising concerns about the predictability of clinical transporter-based drug-drug interactions (DDIs) from in vitro data."	( ITC commentary on the prediction of digoxin clinical drug-drug interactions from in vitro transporter assays. Galetin, A; Kalvass, JC; Lee, CA; Zamek-Gliszczynski, MJ, 2014)	0.9
"Physiologically based pharmacokinetic modeling was applied to characterize the potential drug-drug interactions for ruxolitinib."	( Predicting drug-drug interactions involving multiple mechanisms using physiologically based pharmacokinetic modeling: a case study with ruxolitinib. Fraczkiewicz, G; Shi, JG; Williams, WV; Yeleswaram, S, 2015)	0.42
"Probe drug cocktails are used clinically to assess the potential for drug-drug interactions (DDIs), and in particular, DDIs resulting from coadministration of substrates and inhibitors of cytochrome P450 enzymes."	( The Use of Transporter Probe Drug Cocktails for the Assessment of Transporter-Based Drug-Drug Interactions in a Clinical Setting-Proposal of a Four Component Transporter Cocktail. Ebner, T; Ishiguro, N; Taub, ME, 2015)	0.42
" The permeability of nalfurafine across human P-glycoprotein (P-gp)-expressing LLC-PK1 cells was investigated to evaluate drug-drug interactions (DDI) involving the P-gp efflux transporter of nalfurafine."	( Drug-Drug Interactions of a Novel κ-Opioid Receptor Agonist, Nalfurafine Hydrochloride, Involving the P-Glycoprotein. Ando, A; Miyamoto, Y; Ohzone, Y; Sasago, S, 2016)	0.43
" However, the digitalization therapy involves dose titration and can exhibit drug-drug interaction."	( Strategy for the Prediction of Steady-State Exposure of Digoxin to Determine Drug-Drug Interaction Potential of Digoxin With Other Drugs in Digitalization Therapy. Srinivas, NR, )	0.38
" However, digoxin is rarely used in HIV patients; hence, digoxin toxicity due to drug-drug interaction is not widely recognised."	( Life-threatening digoxin toxicity due to drug-drug interactions in an HIV-positive man. Heatley, MK; Roberts, B; Yoganathan, K, 2017)	1.2
" In this trial, the doses of metformin and furosemide as putative perpetrators were reduced to eliminate their drug-drug interaction (DDI) with rosuvastatin."	( Optimization of a drug transporter probe cocktail: potential screening tool for transporter-mediated drug-drug interactions. Ebner, T; Gansser, D; Giessmann, T; Hohl, K; Hutzel, S; Ishiguro, N; Müller, F; Schmidt, S; Sharma, A; Stopfer, P; Taub, ME, 2018)	0.48
" To our knowledge, there have been no published cases of clinically significant posaconazole-digoxin drug-drug interactions."	( Posaconazole-digoxin drug-drug interaction mediated by inhibition of P-glycoprotein. Bullard, HM; Churpek, J; Knoebel, RW; Shumaker, AC, 2019)	1.1
"A three-period digoxin-bupropion drug-drug interaction study was performed in cynomolgus monkeys to assess the effect of bupropion and its metabolites on digoxin disposition."	( Evaluation of a Potential Clinical Significant Drug-Drug Interaction between Digoxin and Bupropion in Cynomolgus Monkeys. Chen, X; He, J; Hong, K; Jin, J; Lai, W; Li, S; Shen, Y; Xia, C; Xing, H; Xiong, A; Xu, Z; Yan, X; Yu, Y, 2018)	1.06
"Five clinical pharmacology studies evaluated the potential drug-drug interaction between multiple subcutaneous taspoglutide doses and a single dose of lisinopril, warfarin, and simvastatin and multiple doses of digoxin and an oral contraceptive containing ethinylestradiol and levonorgestrel."	( Assessment of Drug-Drug Interactions between Taspoglutide, a Glucagon-Like Peptide-1 Agonist, and Drugs Commonly Used in Type 2 Diabetes Mellitus: Results of Five Phase I Trials. Bogman, K; Brumm, J; Giraudon, M; Hofmann, C; Mangold, B; Niggli, M; Sauter, A; Schmitt, C; Sturm, S; Sturm-Pellanda, C, 2019)	0.7
"25 mg) and rosuvastatin (5 mg) as a new transporter (P-glycoprotein/breast cancer resistance protein/organic anion-transporting polypeptide (OATP)1B1/OATP1B3) probe cocktail (Oita combination) for drug-drug interaction (DDI) studies by demonstrating lack of DDI of digoxin on the pharmacokinetics (PKs) of rosuvastatin, as it was already known that rosuvastatin did not affect digoxin PK."	( No Effect of Digoxin on Rosuvastatin Pharmacokinetics in Healthy Subjects: Utility of Oita Combination for Clinical Drug-Drug Interaction Study. Hasunuma, T; Imai, H; Ishii, Y; Ito, Y; Kuranari, M; Ogawa, O; Ohyama, T; Okubo, A; Otani, N; Takeda, K; Uemura, N; Wakuda, H, 2019)	1.06
" Based on in vitro data, clinical trials were conducted to assess the potential for drug-drug interactions between eliglustat and digoxin (P-glycoprotein substrate), metoprolol (sensitive CYP2D6 substrate), a combined oral contraceptive (CYP3A substrate), and acid-reducing agents."	( Effect of eliglustat on the pharmacokinetics of digoxin, metoprolol, and oral contraceptives and absorption of eliglustat when coadministered with acid-reducing agents. Ibrahim, J; Peterschmitt, MJ; Puga, AC; Ross, L; Thibault, N; Turpault, S; Vu, L; Xue, Y, 2020)	1.02
" The aim of this study was to better understand the drug-drug interaction (DDI) potential of CYP3A and P-gp inhibitors."	( PBPK modeling of CYP3A and P-gp substrates to predict drug-drug interactions in patients undergoing Roux-en-Y gastric bypass surgery. Chan, LN; Chen, KF; Lin, YS, 2020)	0.56
"To characterize the clinical relevance of in vitro drug-drug interaction findings with apararenone (MT-3995), the effects of apararenone on the sensitive substrates of cytochrome P450 3A4 (midazolam) and 2C9 (warfarin), and P-glycoprotein (digoxin), were assessed through a series of studies conducted in healthy volunteers."	( Drug-Drug Interactions of the Nonsteroidal Mineralocorticoid Receptor Antagonist Apararenone With Midazolam, Warfarin, and Digoxin: A Phase 1 Studies in Healthy Volunteers. Kawaguchi, A; Nakamura, T; Shimizu, H, 2020)	0.95
"The findings from this analysis of data from healthy volunteers suggest minimal risk for potential drug-drug interactions between apararenone and other drugs that are likely to be used concurrently in patients."	( Drug-Drug Interactions of the Nonsteroidal Mineralocorticoid Receptor Antagonist Apararenone With Midazolam, Warfarin, and Digoxin: A Phase 1 Studies in Healthy Volunteers. Kawaguchi, A; Nakamura, T; Shimizu, H, 2020)	0.77
" Between Days 11 and 32, capmatinib 400 mg was administered twice daily to ensure the attainment of steady state for drug-drug interaction assessment."	( Effect of capmatinib on the pharmacokinetics of digoxin and rosuvastatin administered as a 2-drug cocktail in patients with MET-dysregulated advanced solid tumours: A phase I, multicentre, open-label, single-sequence drug-drug interaction study. Chen, X; Cui, X; Curigliano, G; Giovannini, M; Grande, E; Marriere, E; Pultar, P; Quinlan, M; Rahmanzadeh, G, 2021)	0.88
"This study demonstrated that capmatinib is an inhibitor of P-gp and BCRP transporters, with clinically relevant drug-drug interaction potential."	( Effect of capmatinib on the pharmacokinetics of digoxin and rosuvastatin administered as a 2-drug cocktail in patients with MET-dysregulated advanced solid tumours: A phase I, multicentre, open-label, single-sequence drug-drug interaction study. Chen, X; Cui, X; Curigliano, G; Giovannini, M; Grande, E; Marriere, E; Pultar, P; Quinlan, M; Rahmanzadeh, G, 2021)	0.88
"The aim of this work is the development of a mechanistic physiologically-based pharmacokinetic (PBPK) model using in vitro to in vivo extrapolation to conduct a drug-drug interaction (DDI) assessment of treosulfan against two cytochrome p450 (CYP) isoenzymes and P-glycoprotein (P-gp) substrates."	( Evaluation of the drug-drug interaction potential of treosulfan using a physiologically-based pharmacokinetic modelling approach. Balazki, P; Baumgart, J; Beelen, DW; Böhm, S; Hemmelmann, C; Hilger, RA; Martins, FS; Ring, A; Schaller, S, 2022)	0.72
"To best promote drug tolerability and efficacy in the clinic, data from drug-drug interaction (DDI) evaluations and subsequent translation of the results to DDI prevention and/or management strategies must be incorporated into the US Food and Drug Administration (FDA) product labeling in a consistent manner because differences in language might result in varied interpretations."	( Analysis of Drug-Drug Interaction Labeling Language and Clinical Recommendations for Newly Approved Drugs Evaluated With Digoxin, Midazolam, and S-Warfarin. Henderson, LM; Ragueneau-Majlessi, I; Steinbronn, CE; Yeung, CK; Yu, J, 2021)	0.83
" Therefore, a drug-drug interaction study was conducted to assess the impact of enasidenib at steady state on the pharmacokinetics of several probe compounds in patients with relapsed or refractory acute myeloid leukemia or myelodysplastic syndrome, including the probes herein described in this article, digoxin and rosuvastatin."	( Assessment of Transporter-Mediated Drug Interactions for Enasidenib Based on a Cocktail Study in Patients With Relapse or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome. Carayannopoulos, L; Cheng, Y; Li, Y; Reyes, J; Tong, Z; Wang, X; Zhou, S, 2022)	0.9
" In vitro studies demonstrate OM as a substrate and inhibitor of P-glycoprotein (P-gp), which can result in drug-drug interactions."	( Pharmacokinetic Drug-Drug Interaction Study of Omecamtiv Mecarbil With Amiodarone and Digoxin in Healthy Subjects. Abbasi, S; Dutta, S; Flach, S; Hsu, CP; Hutton, S; Jafarinasabian, P; Lee, E; Sohn, W; Trivedi, A; Zhang, H, 2022)	0.94
" This study aimed to establish a physiologically based pharmacokinetic (PBPK) model of rifampicin to predict the P-gp-mediated drug-drug interactions (DDIs) and assess the DDI impact in the intestine, liver, and kidney."	( Robust physiologically based pharmacokinetic model of rifampicin for predicting drug-drug interactions via P-glycoprotein induction and inhibition in the intestine, liver, and kidney. Asaumi, R; Nunoya, KI; Sugiyama, Y; Taskar, KS; Yamaura, Y, 2022)	0.72
" Understanding potential drug-drug interactions (DDIs) informs proper dosing when co-administering tucatinib with other therapies."	( Evaluation of Safety and Clinically Relevant Drug-Drug Interactions with Tucatinib in Healthy Volunteers. Abdulrasool, LI; Endres, CJ; Lee, A; Mayor, JG; Rustia, EL; Sun, H; Topletz-Erickson, A; Walker, L, 2022)	0.72
" Based on nonclinical in vitro characterization of gepotidacin metabolism, two phase I studies were conducted in healthy participants to investigate clinical drug-drug interactions (DDIs)."	( Clinical assessment of gepotidacin (GSK2140944) as a victim and perpetrator of drug-drug interactions via CYP3A metabolism and transporters. Barth, A; Brimhall, DB; Dumont, EF; Nguyen, D; Perry, CR; Shabbir, S; Srinivasan, M; Swift, B; Thomas, S; Zamek-Gliszczynski, MJ, 2023)	0.91
" Based on these results, a clinical drug-drug interaction study to evaluate the effect of ensitrelvir on the pharmacokinetics of P-gp, BCRP, OATP1B1, OATP1B3, and OCT1 substrates was conducted with a cocktail approach using digoxin (P-gp substrate), rosuvastatin (BCRP, OATP1B1, and OATP1B3 substrate), and metformin (OCT1 substrate)."	( Evaluation of Drug-Drug Interactions of Ensitrelvir, a SARS-CoV-2 3CL Protease Inhibitor, With Transporter Substrates Based on In Vitro and Clinical Studies. Fukuhara, T; Kubota, R; Kuwata, A; Matsuo, Y; Matsuzaki, T; Oka, R; Shimizu, R; Sonoyama, T, 2023)	1.09

Bioavailability

An encapsulated solution of digoxin has been repeatedly shown to have greater bioavailability than tablet forms of the drug. Macrolide antibiotics appear to be able to enhance the oral bioavailability ofDigoxin by altering the gastrointestinal flora that metabolize digoxin to less active dihydro metabolites.

Excerpt	Reference	Relevance
" These changes suggest interference with the bioavailability of digoxin by SSA."	( Effect of sulfasalazine on digoxin bioavailability. Blaug, SM; Brown, DD; Cheng, FH; Guillory, JK; Juhl, RP; Summers, RW, 1976)	0.79
"Although oral drug bioinequivalence has been attributed to a number of causes (excipients, dosage form, variation in dissolution time, and aging) less is known about bioavailability problems of topical medications in ophthalmology."	( Bioavailability and generic prescribing. Mindel, JS, )	0.13
"The bioavailability of tablet formulations averages about 60% for digoxin, 75% for beta-acetyldigoxin, and 75% for beta-methyldigoxin."	( Bioavailability of digoxin: some pitfalls and problems. Keller, F; Rietbrock, N, 1977)	0.82
" Data are presented suggesting that at least some variation in the bioavailability of orally administered digoxin arises from observed variations in gastric pH; these variations influence the extent to which hydrolysis occurs and, thus, modify the composition of digoxin species available for absorption."	( Kinetics of digoxin stability in aqueous solution. Shaffer, RD; Sternson, LA, 1978)	0.85
" This trend, however, preceded the publicity on potency and bioavailability, and in the case of lanoxin was apparent during the time that bioavailability fell."	( Digoxin prescribing in general practice 1967--77. Pedoe, HD, 1978)	1.7
"The bioavailability of digoxin from 3 silica matrix formulations was assessed in single-dose crossover studies in 12 healthy human volunteers: digoxin/silica matrix tablets (I, Digacin), digoxin/silica matrix in capsule form (II) and digoxin/silica matrix dragées, protected against gastrict juice by film coating (III)."	( [Enhanced bioavailability of digoxin from silica matrix formulations (author's transl)]. Asmussen, B; Flasch, H; Heinz, N, 1978)	0.86
", serum peak height, time of the peak, area under the serum level--time curve (AUC), and area above the Q--S2I (electromechanical systole) decrease (obtained from polycardiographic evaluation), showed better bioavailability of digoxin capsules than tablets, averaging 36."	( Bioavailability and related heart function index of digoxin capsules and tablets in cardiac patients. Assanelli, D; Astorri, E; Bianchi, G; La Canna, G; Marzo, A; Visioli, O, 1979)	0.69
"The digitalis derivative beta-methyldigoxin has been shown to be quickly and well absorbed from the gut and, in hemodynamic studies, to start acting rapidly after intravenous administration."	( Electrophysiological effects soon after intravenous beta-methyldigoxin. Curry, P; Krikler, D; Mahar, L; Rowland, E, 1979)	0.77
" However, despite continuing concern over the bioavailability of generic digoxin tablets, less than 40% of digoxin prescriptions in this study were written for the innovator's brand-name product (Lanoxin)."	( Digoxin-prescribing. Mostly good news. Becker, LA; Karch, FE; Lasagna, L; Morgan, JP; Sorensen, A; Trabert, N; Weintraub, M, 1979)	1.93
" Recent studies have demonstrated that the bioavailability of gitoxin could be upraised to 100% provided it be given as a hydroalcoholic solution."	( Bioavailability study of gitoxin in a solid dosage form. de Suray, JM; Dodion, L; Hupin, C; Lesne, M; Lorent, M; Versluys, J, 1979)	0.26
" It was not known whether the enchanced bioavailability of the encapsulated digoxin solution could also be demonstrated when given postprandially."	( Greater bioavailability of digoxin solution in capsules. Studies in the postprandial state. Lindenbaum, J, 1977)	0.78
"The bioavailability single doses (0."	( [Comparative bioavailability of three pharmaceutical forms of digoxin]. d'Athis, P; Lucas, A; Thebault, J; Tillement, JP, 1977)	0.5
" Absolute bioavailability (i."	( Absolute bioavailability of digoxin tablets. Beveridge, T; Nüesch, E; Ohnhaus, EE, 1978)	0.55
" Sex-linked differences in the bioavailability of different galenic preparations of digoxin were not confirmed statistically in this trial."	( [Bioavailability and elimination of various digoxin preparations in the beagle dog and their possible sex dependence (author's transl)]. Eltze, M; Gastauer, R; Pabst, J, 1979)	0.75
"A study of relative bioavailability of two digoxin formulations was carried out on 28 healthy volunteer human subjects of both sexes."	( An improvement in digoxin bioavailability. Studies with soft gelatin capsules containing a solution of digoxin. Alvisi, V; Bagni, B; Fersini, C; Longhini, C; Portaluppi, F; Ruina, M, 1979)	0.86
" By inference, cardiotoxicity is related solely to the amount and not the rate of absorption from a given dose of digoxin."	( Transient changes in plasma digoxin concentration and the development of cardiotoxicity. Chapple, DJ; Hughes, R; Johnson, BF, 1977)	0.76
" Variations in bioavailability and intestinal absorption are important factors in the determination of dosage and should be reduced to a minimum by improved pharmaceutical formulations."	( Digoxin therapy: a clinical pharmacokinetic approach. Whiting, B, 1978)	1.7
"In six healthy volunteers the bioavailability of alpha-acetyldigoxin in solution and tablet form was compared with a tablet which in addition to alpha-acetyldigoxin contained the DH-ergot alkaloid Hydergine in identical galenic formulation."	( The bioavailability of alpha-acetyldigoxin from Card-Hydergin--a fixed combination of Hydergine and acetyldigoxin. Klotz, U, 1978)	0.78
"The authors have studied the bioavailability of a commercially available digoxin solution in capsule."	( Bioavailability of digoxin in capsules. Brat, A; Padeletti, L, 1978)	0.82
"The effect of a kaolin--pectin suspension on the bioavailability of orally administered digoxin was evaluated when both drugs were given concomitantly and when their time of administration was separated by 2 hr."	( Influence of kaolin--pectin suspension on digoxin bioavailability. Albert, KS; Ayres, JW; DeSante, KA; DiSanto, AR; Hallmark, MR; Sakmar, E; Stoll, RG; Wagner, JG; Weidler, DJ, 1978)	0.74
" Determination of absolute bioavailability of a given digoxin preparation requires a comparative study using intravenous digoxin as a standard."	( Bioavailability of drugs: the digoxin dilemma. Greenblatt, DJ; Koch-Weser, J; Smith, TW, 1976)	0.79
" Digoxin levels was related to blood nitrogen (p less than 0,01); on the other hand, no relationship between others factors influencing the digoxin bioavailability (age, body weight, associated drug) and digoxin levels could be found."	( [Blood digoxin and treatment of heart failure in aged patients]. Hatt, PY; Jouannot, P; Lavabre, J; Thomas, M, 1976)	1.62
"Seven subjects who underwent jejunoileal bypass surgery for massive obesity participated in a study to examine the relative bioavailability of digoxin before and one to two months after surgery."	( The effect of jejunoileal bypass on the pharmacokinetics of digoxin in man. Horton, H; Jacobs, S; Marcus, FI; Pippin, S; Quinn, EJ; Stafford, M; Zukoski, C, 1977)	0.7
" Factors that affect bioavailability among drugs of the same type (especially oral drugs) include not only disintegration and absorption rates but also the amount of food taken before or with the dose, interactions with other drugs, the physical state of the patient, and the "first-pass effect" upon drug with high liver clearance."	( Drug bioavailability studies. Wagner, JG, 1977)	0.26
"The in vitro dissolution and the bioavailability of two pharmaceutical formulations of digoxin were compared, one being a common commercial tablet form and the other a solution of the glycoside in soft gelatin capsules."	( Bioavailability of digoxin in a new soluble pharmaceutical formulation in capsules. Catenazzo, G; Ghirardi, P; Mantero, O; Marzo, A; Merotti, GC, 1977)	0.81
" Literature reports on the oral bioavailability of solutions and solid dosage forms of digoxin were critically reviewed, but no reliable comparison of the extent and reproducibility of oral absorption of cardioactive agents from administered digoxin or beta-methyldigoxin could be made from the widely variable digoxin studies with nonspecific assays."	( Pharmacokinetics of beta-methyldigoxin in healthy humans II: Oral studies and bioavailability. Garrett, ER; Hinderling, PH; Wester, RC, 1977)	0.77
" 4 The enhanced bioavailability of Lanoxicaps was associated with reduced between-subject variability in plasma concentration."	( The comparability of dosage regimens of Lanoxin tablets and Lanoxicaps. French, J; Johnson, BF; Smith, G, 1977)	0.26
"The bioavailability of digoxin and lanatoside C from tablets and dragees and from solutions of the two substances has been investigated intraindividually in patients on maintenance therapy."	( [Clinical study of the biological availability of lanatoside C and digoxin in long-term tests]. Bodem, G; Dengler, HJ; Hahn, E; Ochs, H, 1977)	0.8
"A new oral digoxin formulation, a digoxin-hydroquinone complex (99% dissolution at 5 min), was evaluated in 12 healthy human volunteers with reference to bioavailability and extent and time of peak serum digoxin levels."	( Bioavailability of digoxin-hydroquinone complex: a new oral digoxin formulation. Azarnoff, DL; Bochner, F; Huffman, DH; Shen, DD, 1977)	0.98
" In a test preparation with a bioavailability of 94."	( [Radioimmunological estimation of digoxin in urine (author's transl)]. Maertin, K; Rietbrock, N, 1977)	0.54
" alpha-acetyldigoxin shows a lower bioavailability than beta-acetyldigoxin even if the alpha-acetylated derivative is incorporated in a matrix of aerosil (SiO2)."	( [Isomerisation and bioavailability of beta- and alpha-acetyldigoxin (author's transl)]. Kuhlmann, J; Maertin, K; Rietbrock, N; Vöhringer, HF, 1977)	0.87
"5 mg doses of digoxin; this is necessary in human bioavailability studies to accurately estimate the total area under the digoxin concentration, time curve from zero to infinite time."	( Sensitive radioimmunoassay for digoxin in plasma and urine. Ayres, JW; Hallmark, MR; Sakmar, E; Wagner, JG, 1977)	0.9
" Rapid dissolution in the intestinal fluids accounts for the high digoxin bioavailability of the tablets."	( Maximal bioavailability of digoxin from tablets and oral solution in steady state. Manninen, V; Ojala, K; Reissell, P, 1976)	0.79
"The bioavailability of digoxin (lanoxin) tablets, oral aqueous solution of digoxin, and capsules containing a solution of digoxin was compared with digoxin given intravenously over 1 and 3 hr."	( Digoxin bioavailability: formulations and rates of infusions. Bressler, R; Dickerson, J; Marcus, FI; Pippin, S; Stafford, M, 1976)	2.01
" Extending the period of urine collection beyond 1 day or the blood sampling period beyond 4 or 8 h does not enhance the reliability or usefulness of digoxin bioavailability studies."	( Assessment of methodology in single-dose studies of digoxin bioavailability. Duhme, DW; Greenblatt, DJ; Koch-Weser, J; Smith, TW, 1976)	0.71
" The absolute bioavailability from the oral preparations in comparison with the infusion was lower for the first 8 h than for the entire 32 h of the investigation; the relative bioavailability from tablets was the same as from the solution for both periods."	( Absorption of beta-methyl-digoxin determined after a single dose and under steady state conditions. Boerner, D; Olcay, A; Schaumann, W; Weiss, W, 1976)	0.56
"Employing a Latin-square design and single-dose studies of bioavailability in 10 normal human volunteers, we tested the hypothesis that antacids and kaolin-pectin might interfere with the bioavailability of orally administered digoxin."	( Decreased bioavailability of digoxin due to antacids and kaolin-pectin. Brown, DD; Juhl, RP, 1976)	0.73
" Maintenance doses can be derived from a simple formula based on the glomerular filtration rate, extra-renal clearance and bioavailability of the digoxin preparation used."	( Digoxin pharmacokinetics: multicompartmental analysis and its clinical implications. Russell, AJ; Sumner, DJ, 1976)	1.9
" Bioavailability was assessed further by comparing the area under a six-hour concentration-time curve, and again the capsules gave a consistently higher value than the tablets."	( A comparison of the bioavailability of digoxin in capsule, tablet, and solution taken orally with intravenous digoxin. Binnion, PF, 1976)	0.52
"In eight healthy volunteers the bioavailability of beta-acetyldigoxin solution and tablets was measured after single and multiple doses."	( Bioavailability of beta-acetyldigoxin after single and repeated doses of tablets and solution. Antonin, KH; Bieck, PR; Klotz, U, 1976)	0.78
"In a randomized crossover study the bioavailability of a single dose of digoxin and of beta-methyl-digoxin tablets was tested in four normal volunteers."	( Bioavailability of digoxin and beta-methyl-digoxin. Cinelli, P; Fantini, F; Gremigni, C; Padeletti, L, 1976)	0.82
" With reference to comparable total absorption rates these results may be representative for a possibly retarded absorption rate of dilazep given as pure substance."	( [Studies on the bioavailability of the individual components from a combination of dilazep and beta-acetyldigoxin (author's transl)]. Prignitz, R; Schaumlöffel, E, 1976)	0.47
"The bioavailability of single doses from 4 randomly selected lots of digoxin from a single manufacturer that were recently marketed in the United States was compared."	( Bioavailability of different lots of digoxin tablets from the same manufacturer. Lindenbaum, J, 1975)	0.76
" This can be ascribed to a higher absorption rate of beta-methyldigoxin from the digestive tract."	( Multiclinical open studies on the effect of beta-methyldigoxin on congestive heart failure with atrial fibrillation. Ito, Y; Kimura, E; Seki, K, 1975)	0.74
"The bioavailability of various formulations of digoxin was assessed after single and multiple doses in a series of crossover studies in human volunteers."	( Superior bioavailability of digoxin solution in capsules. Lindenbaum, J; Mallis, GI; Schmidt, DH, 1975)	0.81
" Serum levels were significantly higher at 8 and 24 hours in those patients who received their first dose intramuscularly compared with those who received their first dose orally, irrespective of the bioavailability of the oral preparation used."	( Treatment with digoxin and measurement of serum digoxin levels after myocardial infarction. McL White, B; Norris, RM; Sharpe, DN, 1975)	0.61
" Bioavailability of oral digoxin preparations can be reliably determined by comparison of the cumulative 2-day excretion of digoxin following a single dose."	( Intersubject variation in absorption of digoxin in normal volunteers. Azarnoff, DL; Huffman, DH; Manion, CV, 1975)	0.83
" The use of the solid phase assay is demonstrated comparing the bioavailability of various digoxin derivatives."	( A solid phase radioimmunoassay for digoxin and its acylated derivatives. Arndts, D, 1975)	0.75
" In a single dose crossover study bioavailability of the oral preparations was compared to an intravenous injection of digoxin as a standard for complete bioavailability."	( [Bioavailability of beta-acetyldigoxin and digoxin (author's transl)]. Flasch, H, 1975)	0.75
"The period of time after administration over which blood level measurements are required to obtain a reliable bioavailability comparison of two or more formulations of the same drug was considered by the analysis of bioavailability data taken from the literature."	( Comparative bioavailabilities from truncated blood level curves. Lovering, EG; McGilveray, IJ; McMillan, I; Tostowaryk, W, 1975)	0.25
"The bioavailability of digoxin in three tablets prepared from materials with different particle sizes was measured in healthy volunteers in a cross-over study using an alcoholic solution of digoxin as a reference standard."	( Effect of particle size on the bioavailability of digoxin. Jounela, AJ; Pentikäinen, PJ; Sothmann, A, 1975)	0.82
" The absorption rate was estimated taking into account the decreasing amount of drug left to be absorbed at different times."	( Absorption of digoxin in man after oral and intrasigmoid administration studied by portal vein catheterization. Andersson, KE; Dencker, H; Göthlin, J; Nyberg, L, 1975)	0.62
"The bioavailability of digoxin in solution was studied in 4 newbron infants with heart failure."	( Absorption of digoxin in infants. Andersson, KE; Wettrell, G, 1975)	0.93
" Digoxin-Sandoz tablets were shown to have a constant bioavailability and to produce plasma concentrations very similar to ""new'' Lanoxin."	( Bioavailability studies with Digoxin-Sandoz and Lanoxin. Beveridge, T; Kalberer, F; Nüesch, E; Schmidt, R, 1975)	1.46
"A review is presented of the more significant aspects of recent bioavailability studies on digoxin tablets that have led to the identification of variations among commercially available tablets and of the correlation of the methods commonly used in such bioavailability evaluations."	( Digoxin tablets--a review of the bioavailability problems. Sim, SK, 1976)	1.92
" Enhanced bioavailability of the capsules was not affected by altered volume of contained solvent."	( A completely absorbed oral preparation of digoxin. Bye, C; Johnson, BF; Jones, G; Sabey, GA, 1976)	0.52
"Differences in bioavailability of many drugs from their various dosage forms have been shown to be relatively common in human medicine."	( Bioavailability and bioinequivalence of drug formulations in small animals. Watson, AD, 1992)	0.28
" Trough values during steady state and 24 h AUC were used to calculate digoxin bioavailability for tablets and oral solution."	( [Absolute bioavailability of beta-acetyldigoxin from tablets and drops in healthy subjects]. Dammann, HG; Dreyer, M; Endell, W; Iven, H; Rudolph, M, 1992)	0.78
" The nasal and intestinal absorption rate of digoxin was reduced by an increase in the perfusion volume."	( Nasal absorption of digoxin in rats. Kato, Y; Kimura, R; Sato, M; Yagi, N; Yamada, S, 1992)	0.87
"The bioavailability of digoxin in solution (Lanoxicaps, 90-100 percent) is superior to that of Lanoxin tablets (60-80 percent) in young healthy volunteers."	( Comparison of steady-state serum concentrations of digoxin in tablets (Lanoxin) and capsules (Lanoxicaps) in the elderly. Gribnau, FW; Hooymans, PM; Pouwels, MJ; van der Aa, GC, 1991)	0.84
" It is well established that digitalis compounds present great variability in their respective "in vivo" bioavailability in human (60-90% for digoxin, 0% for ouabain)."	( Intestinal absorption of drugs: digitalis binding and transport by brush-border membrane vesicles from human duodenum. Coppens, R; Di Marino, V; Durand, A; Masset, D; Placidi, M; Rahmani, R; Rahmani-Jourdheuil, D, 1991)	0.48
" Omeprazole, and presumably other gastric-acid inhibitors, may increase the bioavailability of unchanged digoxin."	( Influence of gastric acidity on the bioavailability of digoxin. Cohen, AF; Hoogkamer, H; Kroon, R; Schoemaker, R; van Vliet, A, 1991)	0.74
" The apolar, fat soluble digitoxin is very well absorbed from the intestine, its onset of action is slow, binds to a high degree to albumin and undergoes enterohepatic recirculation which accounts for a long elimination half time and stability of plasmatic levels."	( [The past and the present of cardiac glycosides. III. Pharmacokinetics]. Synek, P, 1991)	0.28
"Moricizine is well absorbed after oral administration and undergoes extensive first-pass metabolism."	( Clinical pharmacokinetics of moricizine. Barbey, JT; Schwartz, SL; Siddoway, LA; Woosley, RL, 1990)	0.28
" After oral digoxin treatment, amiodarone increased peak serum concentration, total area under the serum concentration-time curve (AUC), and 5-day urinary recovery of the glycoside, without changes in peak time and absorption rate constant."	( Effects of amiodarone on oral and intravenous digoxin kinetics in healthy subjects. Basadonna, O; Dalla-Volta, S; Fantin, M; Gaion, RM; Maragno, I; Santostasi, G, 1987)	0.91
" Thirty and 45 min after the intake of digoxin, the serum digoxin concentration was significantly higher during exercise compared with rest, indicating increased absorption rate during exercise."	( Effect of physical exercise on the pharmacokinetics of digoxin during maintenance treatment. Andersson, K; Jogestrand, T, 1989)	0.79
"Amlodipine, a dihydropyridine calcium antagonist, was synthesized in an attempt to develop a compound with a pharmacokinetic profile characteristic of this class, which would also have an increased oral bioavailability and extended clearance time."	( The pharmacokinetic profile of amlodipine. Abernethy, DR, 1989)	0.28
" The present data suggested that the sublingual administration of the rapid dissolving form of gamma-cyclodextrin complex may be useful for improving the bioavailability of digoxin due to the prevention of acid hydrolysis in stomach and the enhancement of drug absorption rate."	( [Enhanced bioavailability of digoxin by gamma-cyclodextrin complexation: evaluation for sublingual and oral administrations in humans]. Seo, H; Uekama, K, 1989)	0.76
" The dose was further adjusted for factors such as renal and hepatic function, the bioavailability of different formulations, and the size of the patient."	( Serum digoxin concentrations in canine congestive heart failure. Berry, WL; Bland-van den Berg, P; Kruse, MM; Tobias, AH; Tubbesing, UH, 1989)	0.76
" The geometric mean and nonparametric 95% confidence limits of digoxin relative bioavailability were 97% (93%-103%)."	( Effect of urapidil on steady-state serum digoxin concentration in healthy subjects. Haerlin, R; Klingmann, I; Mosberg, H; Solleder, P; Wurst, W, 1989)	0.78
"The relative steady-state bioavailability of two oral digoxin dosage forms was studied in 17 subjects with malabsorption syndromes."	( Absorption of digoxin from tablets and capsules in subjects with malabsorption syndromes. Bustrack, JA; Fitch, DD; Hammond, JE; Heizer, WD; Hull, JH; Pittman, AW, 1989)	0.89
" Although there were no statistically significant differences in lisinopril pharmacokinetics during single or combined treatment, serum and urinary parameters suggest that bioavailability may be enhanced slightly during combined treatment."	( A study of the potential pharmacokinetic interaction of lisinopril and digoxin in normal volunteers. Dews, IM; Kelly, JG; Marks, C; Morris, F; Stephens, JD; Vandenburg, MJ, 1988)	0.51
" Among the drugs that can decrease digoxin bioavailability are cholestyramine, antacid gels, kaolin-pectate, certain antimicrobial drugs and cancer chemotherapeutic agents."	( Pharmacokinetic interactions between digoxin and other drugs. Marcus, FI, 1985)	0.82
" Certain antibiotics including sulphasalazine, neomycin and aminosalicylic acid reduce digoxin absorption while others, including erythromycin and tetracycline, increase the bioavailability of digoxin in some patients."	( Pharmacokinetic interactions with digoxin. Johnson, BF; Rodin, SM, 1988)	0.78
"001) was observed only in patients with a high plasma felodipine level, which may have been caused by changes in the absorption rate in those patients."	( Digoxin-felodipine interaction in patients with congestive heart failure. Dunselman, PH; Kuntze, CE; Lie, KI; Scaf, AH; Wesseling, H, 1988)	1.72
" The bioavailability was reduced by colestipol 80%, by cholestyramine 95% and by activated charcoal 99."	( Effects of resins and activated charcoal on the absorption of digoxin, carbamazepine and frusemide. Hirvisalo, EL; Kivistö, K; Neuvonen, PJ, 1988)	0.52
" The half-life of absorption t1/2a, Cmax and tmax, half-life of elimination t1/2z, and area under the curve (AUC) were compared to evaluate the influence on the bioavailability of gitoformate."	( [Postprandial delay of drug absorption in a gitoformate model]. Kubin, S; Menke, G; Rietbrock, N; Woodcock, BG, 1987)	0.27
"In rabbits, a three way cross-over test was carried out to assess bioavailability of digoxin from commercially available 'Deriphyllin-Digoxin' tablets."	( Assessment of bio(in)equivalence of deriphyllin-digoxin in human volunteers. II. Evaluation of rabbits as qualitative animal model. Bansinath, M; Chopra, KS; Ghosh, SS; Mathur, VS; Shukla, VK, 1986)	0.75
"Elderly and old patients with subacute myocardial infarction showed elevated gastrointestinal digoxin absorption rates and a tendency to increased bioavailability of the drug, as compared to similar parameters in infarction-free patients of the same age, so that blood digoxin peaks were higher in the former."	( [Pharmacokinetics of digoxin in middle-aged and elderly patients in the subacute period of myocardial infarction]. Glezer, MG; Grigor'eva, EA; Iakovlev, SV; Kholodov, LE; Mikhaĭlov, AA, 1986)	0.81
" The increased dosage requirement could partly be explained by reduced bioavailability due to intestinal conversion of digoxin."	( The significance of the enterohepatic circulation on the metabolism of digoxin in patients with the ability of intestinal conversion of the drug. Klitgaard, NA; Nørregaard-Hansen, K; Pedersen, KE, 1986)	0.71
" In six volunteers the bioavailability of 16AG from two PAG tablet formulations (1."	( On the pharmacokinetics of 16-acetyl-gitoxin and its bioavailability from pengitoxin-containing tablet formulations. Haustein, KO, 1986)	0.27
" The drug is completely absorbed from the gastrointestinal tract, but first-pass extraction reduces oral bioavailability to approximately 60%."	( Pharmacokinetics and metabolism of bepridil. Benet, LZ, 1985)	0.27
" Like tetracycline, erythromycin also appears to have the potential for increasing the bioavailability of digoxin in patients who excrete high amounts of reduced digoxin metabolites, apparently through destruction of the gut flora that form these compounds."	( Pharmacokinetic interactions of the macrolide antibiotics. Ludden, TM, )	0.34
" The bioavailability of digoxin is appreciably less than that of digitoxin, averaging about two-thirds to three-fourths of the equivalent dose given intravenously in the case of currently available tablet formulations."	( Pharmacokinetics, bioavailability and serum levels of cardiac glycosides. Smith, TW, 1985)	0.58
" We investigated possible differences in the effects of high-dose cancer chemotherapy on the relative bioavailability of digoxin administered in tablet form (Lanoxin; Burroughs Wellcome Co."	( Effects of high-dose cancer chemotherapy on the absorption of digoxin in two different formulations. Bjornsson, TD; Christenson, R; Huang, AT; Jacob, DS; Roth, P, 1986)	0.72
"An encapsulated solution of digoxin has been repeatedly shown to have greater bioavailability than tablet forms of the drug."	( Variability of steady-state digoxin kinetics during administration of tablets or capsules. Budnitz, E; Johnson, BF; Lindenbaum, J; Marwaha, R, 1986)	0.86
" The model correctly predicts bioavailability as a function of particle size for both of these poorly soluble drugs."	( Mixing-tank model for predicting dissolution rate control or oral absorption. Dressman, JB; Fleisher, D, 1986)	0.27
"The confidence interval approach to bioavailability assessment depends first on selection of the confidence level, usually 95%, and then determination of the confidence limits for the expected bioavailability ratio AUC(Test)/AUC(Reference)."	( Generalization of distribution--free confidence intervals for bioavailability ratios. Diletti, E; Steinijans, VW, 1985)	0.27
" Bioavailability was determined from steady-state, 24-hour area under the serum concentration-time curve (AUC, ng X h/mL) and from 0- and 24-hour trough serum digoxin concentrations (ng/mL)."	( A steady-state evaluation of the effects of propantheline bromide and cholestyramine on the bioavailability of digoxin when administered as tablets or capsules. Brown, DD; Hull, JH; Long, RA; Schmid, J, )	0.54
"Data on monthly totals of cardiac deaths in England and Wales were examined in different ways to see whether there were any unexplained fluctuations in rates both at the time of an unplanned increase in the bioavailability and therefore the potency of the Lanoxin brand of digoxin in May 1972 and also when there was a coordinated increase in the bioavailability of other brands in October 1975."	( Changing digoxin potency and cardiac mortality in England and Wales 1968-76. Tunstall-Pedoe, H, 1985)	0.86
"After a single dose the absorption rate of the new tablets was about twice as great as the old, both in young subjects and in the elderly patients."	( Comparative study of the absorption, plasma levels, and urinary excretion of the "new" and the "old" Lanoxin. Bjerkelund, CJ; Falch, D; Teien, A, 1973)	0.25
"Three subjects were first given a digoxin tablet in the fasting state and subsequently received the same formulation in the fed state, to simulate a spurious oral bioavailability difference."	( Pharmacokinetics of digoxin: interpreting bioavailability. Halkin, H; Melmon, KL; Sanchez, N; Sheiner, LB, 1973)	0.85
"Though established quality control standards were maintained, the bioavailability of digoxin from Lanoxin tablets produced in the United Kingdom fell in 1969, and was restored in 1972."	( Biological availability of digoxin from Lanoxin produced in the United Kingdom. Fowle, AS; Fox, J; Johnson, BF; Lader, S; Munro-Faure, AD, 1973)	0.77
" The data are presented suggesting that CyDs are useful for improving the oral bioavailability of digoxin."	( Effect of cyclodextrins on the acid hydrolysis of digoxin. Fujinaga, T; Hirayama, F; Ikeda, K; Kurono, Y; Otagiri, M; Uekama, K, 1982)	0.73
" The bioavailability of digoxin elixir in newborns and infants is similar to adults; however, the apparent volume of distribution has been reported to be greater in infants than in adults."	( Digoxin pharmacokinetics and dosage requirements in pediatric patients. Bendayan, R; McKenzie, MW, )	1.88
" The high hepatic extraction results in low systemic bioavailability (20%) after oral drug administration."	( Clinical pharmacokinetics of verapamil. Blouin, RA; Hamann, SR; McAllister, RG, )	0.13
" Available evidence suggests that absorption of amiodarone following oral administration is erratic and unpredictable; oral bioavailability ranges from 22 to 86%."	( Clinical pharmacokinetics of amiodarone. Kates, RE; Latini, R; Tognoni, G, )	0.13
" These results show that amiodarone increases digoxin bioavailability by a mechanism which appears to be independent of changes in drug elimination."	( Influence of amiodarone on oral digoxin bioavailability in healthy volunteers. Gaion, RM; Maragno, I; Paleari, C; Santostasi, G, 1984)	0.81
" Furthermore, because of the bioavailability of the pharmaceutical formulation, the dose the patient "takes" may not be the one that he or she actually gets."	( Effect of bioavailability on dose-response relationships. Goldman, P, 1984)	0.27
" Thus, the absorption rate of digoxin from the enteric-coated formulation was markedly reduced but at the cost of a variable reduction in the amount absorbed."	( Fasting and postprandial absorption of digoxin from a microencapsulated formulation. Bergdahl, B; Bogentoft, C; Jonsson, UE; Magnusson, JO, 1983)	0.82
" The mean bioavailability (F) was 23."	( A pharmacokinetic study of digoxin in the horse. Brumbaugh, GW; Enos, LR; Kaneko, JJ; Thomas, WP, 1983)	0.56
" The use of highly bioavailable capsules in subjects with heavy DRP production should minimize metabolic inactivation during digoxin therapy."	( Decreased digoxin cardioinactive-reduced metabolites after administration as an encapsulated liquid concentrate. Butler, VP; Dobkin, JF; Lindenbaum, J; Rund, DG; Saha, JR, 1983)	0.87
"Simultaneous oral administration of digoxin and three benzamides (Metoclopramide, Alizapride, Bromopride) to the rat, modify digoxin's pharmacokinetic parameters: peak plasma concentration, elimination phase half life and bioavailability (Bromopride, Alizapride in function with dose-level)."	( Pharmacokinetic study of digoxin-benzamide interaction in the rat. Jacquot, C; Metivier, B; Renault, H; Servin, A, 1984)	0.85
" The delayed time to peak after a single dose of digoxin or digitoxin during cytostatic drug therapy shows that rate of absorption of both glycosides is reduced."	( Inhibition of digoxin absorption but not of digitoxin during cytostatic drug therapy. Kuhlmann, J, 1982)	0.88
"The efficacy on congestive heart failure of metildigoxin (beta-methyldigoxin, MD), a derivative of digoxin (DX), which had a good absorption rate from digestive tract, was examined in a double blind study using a gorup comparison method."	( Effect of metildigoxin (beta-methyldigoxin) on congestive heart failure as evaluated by multiclinical double blind study. Kimura, E; Sakuma, A, 1980)	0.87
" constant) bioavailability may contribute to a further decrease of the frequency of toxic side-effects in future."	( [Effective concentration and dosage for cardiac glycosides]. Förster, W; Weiss, M, 1980)	0.26
" Dose-dependent changes in rate and extent of absorption, bioavailability (saturation of first-pass metabolism), distribution (saturation of protein binding sites) and metabolism are discussed."	( Pharmacokinetics of drug overdose. Benowitz, NL; Pond, S; Rosenberg, J, )	0.13
" The bioavailability and biotransformation of digoxin do not vary between healthy subjects and patients with renal insufficiency."	( Digitalis therapy in renal failure with special regard to digitoxin. Rietbrock, N; Vöhringer, HF, 1981)	0.52
" Our laboratory carried out a study of digoxin bioavailability in which a standard digoxin dose of 500 micrograms was given to 16 volunteers and the present radioimmunoassay method was employed to measure digoxin excretion."	( A routine method for the determination of digoxin in urine by radioimmunoassay. Bustrack, JA; Christenson, RH; Hammond, JE; Hull, JH, 1982)	0.8
"The bioavailability of digoxin and beta-methyl-digoxin (BMD) was tested with a single dose on the grounds of peak serum concentration, tmax, area under the serum concentration-time curve and the cumulative 24 hour urinary excretion on one group of patients with liver disease (n = 20) and one with gastrointestinal disease (n = 10)."	( [Bioavailability of digoxin and beta-methyl-digoxin in patients with liver and gastro-intestinal diseases ]. Bütler, A; Hess, T; Stucki, P, 1982)	0.9
"In connection with the function of a newly constructed absorption model the problem of interpretation of values obtained by models in regard of bioavailability is discussed."	( [Feasibility of the in vitro evaluation of bioavailability. 3: Method of operation of a newly-developed absorption model and results obtained with it]. Buchmann, E; Fuchs, G; Fürst, W; Neubert, R; Stütz, B, 1982)	0.26
"The absolute bioavailability of the digoxin tablet (dilanacin new) newly developed by the VEB Arzneimittelwerk Dresden is compared with the bioavailability of the old preparation, and it is referred to the clinical importance of the difference established."	( [Bioavailability of Dilanacin and Dilanacin new]. Gruber, G; Sorger, D, 1982)	0.54
"The drug release of four brands of digoxin tablets (A, B, C, D) with known bioavailability was examined using three liberation systems."	( [Drug release in vitro from digoxin formulations with high bioavailability (author's transl)]. Asmussen, B; Heinz, N, 1980)	0.83
" Bioavailability was measured by the urinary recovery of digoxin in the eight days after each dosing."	( The effects of some organic solvents on the absorption of digoxin by man. Fowle, AS; French, J; O'Grady, J, 1981)	0.75
" Multiple samples of urine and plasma collected in a single dose bioavailability trial in normal human volunteers were assayed by one of these specific methods as well as by the usual direct nonspecific RIA method."	( Specific and sensitive assays for digoxin in plasma, urine and heart tissue. Morais, JA; Sakmar, E; Stetson, PL; Wagner, JG; Zlotecki, RA, 1981)	0.54
"The urinary excretion of the relatively cardioinactive reduced metabolites of digoxin, dihydrodigoxin and related compounds was measured by radioimmunoassay in 131 normal subjects during studies of the bioavailability of digoxin preparations."	( Urinary excretion of reduced metabolites of digoxin. Butler, VP; Lindenbaum, J; Rund, DG; Tse-Eng, D, 1981)	0.75
"The reproducibility of drug absorption within a given subject as well as the evaluation of bioavailability of two digoxin dosage forms were studied."	( The assessment of the intrasubject variability in digoxin absorption in man from two oral dosage forms. Ayers, JW; Chao, GC; Hallmark, M; Sakmar, E; Schwartz, RA; Stoll, RG; Wagner, JG; Weidler, DJ; Yacobi, A, 1981)	0.73
" In four normal volunteers taking digoxin daily for four weeks, urinary excretion of DRPs was greatest after a poorly absorbed tablet was ingested, and least after intravenous administration, Stool cultures from subjects known to make DRPs in vivo ("excretors") converted digoxin to DRPs; cultures from nonexcretors did not."	( Inactivation of digoxin by the gut flora: reversal by antibiotic therapy. Butler, VP; Lindenbaum, J; Rund, DG; Saha, JR; Tse-Eng, D, 1981)	0.89
" Preliminary work supported the assumptions that the steady state glycoside concentration achieved was proportional to the daily dose given to an individual, and that the bioavailability of the different tablet presentations was similar for either glycoside."	( Evaluation of medigoxin in outpatients. Deshmukh, AA; Dobbs, SM; Gettins, DA; Humm, RP; Nicholson, PW; Rodgers, EM; Smith, WR, 1981)	0.61
" The oral bioavailability of bis in azotemic dogs relative to an intravenous dose was approximately 46%."	( Metabolism and rate of elimination of digoxigenin bisdigitoxoside in dogs before and during chronic azotemia. Gierke, KD; Goldman, S; Graves, PE; Marcus, FI; Mayersohn, M; Perrier, D, 1980)	0.26
" Digoxin elixir was rapidly absorbed, with a mean bioavailability estimate of 71."	( Pharmacokinetics, bioavailability, and dosage regimens of digoxin in dogs. Button, C; Gross, DR; Johnston, JT; Yakatan, GJ, 1980)	1.42
"The pharmacokinetics of IV administered digoxin and the bioavailability of intragastrically administered powdered digoxin tables suspended in water were investigated in 6 clinically normal adult horses by 125I radioimmunoassay."	( Digoxin pharmacokinetics, bioavailability, efficacy, and dosage regimens in the horse. Button, C; Gross, DR; Johnston, JT; Yakatan, GJ, 1980)	1.97
" Thus, the bioavailability of orally administered digoxin tablets in healthy volunteers is dose-independent over an 8-fold range of doses."	( Effect of dose on bioavailability of oral digoxin. Bodem, G; Greenblatt, DJ; Ochs, HR, 1981)	0.78
" Carvedilol appears to increase digoxin's oral bioavailability as well as renal elimination."	( Effects of long-term oral carvedilol on the steady-state pharmacokinetics of oral digoxin in patients with mild to moderate hypertension. Boyle, DA; Chandler, MH; Clifton, GD; Field, CJ; Smith, DA; Wermeling, DP, )	0.64
" Studies investigating the effect of food on fluvastatin pharmacokinetics have demonstrated marked reductions in the rate of bioavailability (Cmax) of 40% to 60%."	( Pharmacokinetics of fluvastatin and specific drug interactions. Hwang, DS; Jokubaitis, LA; Robinson, WT; Smith, HT; Troendle, AJ, 1993)	0.29
" Accordingly, the absorption rate of lidocaine by heart tissues increased with time up to 60 min while that of digoxin decreased with time."	( Distribution of lidocaine and digoxin in heart tissues and aorta following intrapericardial administration. Darsinos, JT; Karli, JN; Kontoyanni, M; Krumholz, B; Levis, GM; Moulopoulos, SD; Pistevos, AK; Samouilidou, EC; Theodorakis, MG, 1993)	0.79
" Bioavailability after oral administration was 21."	( Pharmacokinetics of digoxin administered to horses with congestive heart failure. Reef, VB; Reimer, JM; Sweeney, RW, 1993)	0.61
" Digoxin dry elixir might be a useful solid dosage form to improve the dissolution rate and bioavailability of poorly water-soluble digoxin compared to digoxin powder alone."	( Development of digoxin dry elixir as a novel dosage form using a spray-drying technique. Kim, CK; Yoon, YS, )	1.39
" An absolute bioavailability of approximately 6% has been reported with large inter- and intra-subject variability."	( Human pharmacokinetics of tiludronate. Necciari, J; Sansom, LN; Thiercelin, JF, 1995)	0.29
" Estimates of oral clearance (Cl), volume of distribution, and absorption rate constant of digoxin were generated from plasma digoxin concentrations using nonlinear mixed effects modeling, and the effect of epoprostenol on Cl of digoxin was evaluated by univariate analysis."	( The effects of epoprostenol on drug disposition. I: A pilot study of the pharmacokinetics of digoxin with and without epoprostenol in patients with congestive heart failure. Carlton, LD; Mattson, CN; Patterson, JH; Schmith, VD, 1996)	0.73
"A previously validated physiologically based pharmacokinetic model was used to examine whether epoprostenol-induced increases in gastrointestinal blood flow (Qg) could alter digoxin systemic bioavailability to a clinically significant extent in severe congestive heart failure (CHF) patients."	( Physiologic pharmacokinetic modeling of gastrointestinal blood flow as a rate-limiting step in the oral absorption of digoxin: implications for patients with congestive heart failure receiving epoprostenol. Brouwer, KL; Carlton, LD; Pollack, GM, 1996)	0.7
" lentum, which can lead to an increase in digoxin bioavailability and blood concentrations in patients in whom this intestinal metabolic pathway is present."	( Clarithromycin-induced digoxin intoxication. Laberge, P; Martineau, P, 1997)	0.87
"Macrolide antibiotics appear to be able to enhance the oral bioavailability of digoxin by altering the gastrointestinal flora that metabolize digoxin to less active dihydro metabolites, thus leading to increased serum digoxin concentrations and possible digoxin toxicity in select patients stabilized on digoxin therapy."	( Digoxin-macrolide drug interaction. Bizjak, ED; Mauro, VF, 1997)	1.97
" Co-administration of candesartan cilexetil with HCTZ produced a statistically significant increase in the bioavailability and Cmax values for candesartan (18% and 25%, respectively)."	( Pharmacokinetic drug interaction studies with candesartan cilexetil. Högemann, A; Jonkman, JH; Lins, R; Sennewald, R; van Heiningen, PN; van Lier, JJ, 1997)	0.3
" Antibiotics may increase the oral bioavailability of digoxin, leading to increases in its plasma concentration."	( Pharmacokinetic interaction of sparfloxacin and digoxin. Conway, S; Dorr, MB; Hunt, TL; Johnson, RD; Talbot, GH, 1999)	0.81
"Grapefruit juice (GJ) is known to increase the oral bioavailability of many CYP3A-substrates by inhibiting intestinal phase-I metabolism."	( Grapefruit juice activates P-glycoprotein-mediated drug transport. Benet, LZ; Christians, U; Silverman, JA; Soldner, A; Susanto, M; Wacher, VJ, 1999)	0.3
"The bioavailability of digoxin generic tablets manufactured in Korea (formulations A & B) were compared to a standard (formulation C; Lanoxin brand digoxin, Burroughs Wellcome, USA) in 12 healthy Korean male volunteers (mean age 31."	( Bioavailability of digoxin tablets in healthy volunteers. Jones, DW; Lee, CH; Park, YJ; Sands, CD; Trang, JM, 1994)	0.93
" The present study was carried out to determine the use pattern of digoxin in Estonia and bioavailability of the local market leader preparation in comparison with Lanoxin."	( Digoxin: use pattern in Estonia and bioavailability of the local market leader. Irs, A; Oselin, K; Pähkla, R; Rootslane, L, 1999)	1.98
" For the bioequivalence study, a single-blind cross-over randomised two-way single-dose comparative bioavailability study was performed using 14 healthy volunteers."	( Digoxin: use pattern in Estonia and bioavailability of the local market leader. Irs, A; Oselin, K; Pähkla, R; Rootslane, L, 1999)	1.75
" The increasing use of digoxin in Estonia is not caused by low bioavailability of the local market leader but by therapeutic traditions."	( Digoxin: use pattern in Estonia and bioavailability of the local market leader. Irs, A; Oselin, K; Pähkla, R; Rootslane, L, 1999)	2.06
" The significance of the intestinal first pass effect for the bioavailability of the three model drugs, midazolam, cyclosporin and digoxin, has been reviewed."	( [Drug metabolism in the small intestine--the significance for biological availability]. Andersen, VC; Sonne, J, 2000)	0.51
" Absorption rate constant was lower in females and in the presence of concomitant drug treatment."	( Population pharmacokinetics of digoxin in Korean patients. Derendorf, H; Jeon, S; Nagaraja, NV; Park, YJ; Sands, CD, 2000)	0.59
" These results suggest that surfactants such as Cremophor EL and Polysorbate 80 should not only support solubilization but can also modulate the P-glycoprotein system to improve the bioavailability of poorly absorbed drugs."	( Effect of polyoxyl 35 castor oil and Polysorbate 80 on the intestinal absorption of digoxin in vitro. Cloarec, A; Cornaire, G; Decourt, S; Houin, G; Legendre, JY; Saivin, S; Woodley, JF, 2000)	0.53
"We observed a significantly increased bioavailability of digoxin with oral coadministration of talinolol, which is most likely caused by competition for intestinal P-glycoprotein."	( Oral bioavailability of digoxin is enhanced by talinolol: evidence for involvement of intestinal P-glycoprotein. Franke, G; Giessmann, T; Kroemer, HK; Oertel, R; Siegmund, W; Stuhr, M; Terhaag, B; Weinbrenner, A; Westphal, K; Zschiesche, M, 2000)	0.86
" Bioavailability (Cmax and area under the curve) increased approximately in proportion with dose, after single and multiple daily oral doses, over the therapeutic dose range (up to 40-80 mg daily), above which systemic availability of olmesartan increased less than proportionally with increase in dose."	( The pharmacokinetic and metabolic profile of olmesartan medoxomil limits the risk of clinically relevant drug interaction. Kirch, W; Laeis, P; Püchler, K, 2001)	0.31
" At a perfusate concentration of 1 mM, verapamil caused a dramatic increase in [(3)H]digoxin absorption rate from duodenum and jejunum, while the effect in colon was insignificant."	( The role of P-glycoprotein in limiting intestinal regional absorption of digoxin in rats. Borgå, O; Hultkvist-Bengtsson, U; Sababi, M, 2001)	0.77
" Our main objective was to determine whether grapefruit juice alters the bioavailability of digoxin, a P-glycoprotein substrate."	( Effect of grapefruit juice on digoxin pharmacokinetics in humans. Becquemont, L; Brinkmann, U; Funck-Brentano, C; Jaillon, P; Kerb, R; Lebot, M; Verstuyft, C, 2001)	0.82
"Levofloxacin, a broad-spectrum fluoroquinolone, may enhance digoxin bioavailability by eliminating intestinal flora that metabolize digoxin."	( Absence of a pharmacokinetic interaction between digoxin and levofloxacin. Chien, SC; Chow, AT; Natarajan, J; Rogge, MC; Williams, RR; Wong, F, 2002)	0.81
" Modulation of MDR1 expression in these normal cell types can also influence the activity and bioavailability of drugs."	( Functional polymorphisms of the human multidrug resistance (MDR1) gene: correlation with P glycoprotein expression and activity in vivo. Brinkmann, U, 2002)	0.31
" Because nicotine was postulated to be a beneficial component of tobacco smoke for ulcerative colitis, various formulations of nicotine have been developed to improve the local bioavailability within the gastrointestinal tissue."	( Transport mechanisms of nicotine across the human intestinal epithelial cell line Caco-2. Fukada, A; Inui, K; Saito, H, 2002)	0.31
" This work also describes the effects of IL2 on the oral bioavailability of a Pgp substrate (digoxin) and of a Pgp/CYP3A cosubstrate (saquinavir)."	( Effect of interleukin-2 on intestinal P-glycoprotein expression and functionality in mice. Banide, H; Faivre, L; Farinotti, R; Lacour, B; Soursac, M; Tardivel, S; Veau, C, 2002)	0.53
"Our objective was to quantitate the contribution of the genetic polymorphism of the human MDR1 gene to the bioavailability and interaction profiles of digoxin, a substrate of P-glycoprotein."	( Role of human MDR1 gene polymorphism in bioavailability and interaction of digoxin, a substrate of P-glycoprotein. Higuchi, S; Ieiri, I; Irie, S; Kimura, M; Kurata, Y; Morita, T; Ohdo, S; Ohtani, H; Otsubo, K; Sawada, Y; Urae, A, 2002)	0.74
"The bioavailability of digoxin in G/G2677C/C3435, G/T2677C/T3435, and T/T2677T/T3435 subjects were 67."	( Role of human MDR1 gene polymorphism in bioavailability and interaction of digoxin, a substrate of P-glycoprotein. Higuchi, S; Ieiri, I; Irie, S; Kimura, M; Kurata, Y; Morita, T; Ohdo, S; Ohtani, H; Otsubo, K; Sawada, Y; Urae, A, 2002)	0.86
"On the basis of in vitro studies indicating that dipyridamole is an inhibitor for the MDR1 efflux membrane transporter P-glycoprotein, we postulated that dipyridamole could increase the bioavailability of digoxin, a P-glycoprotein substrate."	( Dipyridamole enhances digoxin bioavailability via P-glycoprotein inhibition. Becquemont, L; Brinkmann, U; Dubert, L; El-Morabet, H; Funck-Brentano, C; Jaillon, P; Kerb, R; Strabach, S; Trugnan, G; Verstuyft, C, 2003)	0.82
"The main objective was to determine whether dipyridamole alters the bioavailability of digoxin."	( Dipyridamole enhances digoxin bioavailability via P-glycoprotein inhibition. Becquemont, L; Brinkmann, U; Dubert, L; El-Morabet, H; Funck-Brentano, C; Jaillon, P; Kerb, R; Strabach, S; Trugnan, G; Verstuyft, C, 2003)	0.86
" Recently, a number of polymorphisms in the MDR-1 gene were identified and the T/T genotype at position 3435 in exon 26 was found to correlate with intestinal P-glycoprotein expression and bioavailability of digoxin after oral administration."	( Polymorphism C3435T of the MDR-1 gene predicts response to preoperative chemotherapy in locally advanced breast cancer. Deissler, H; Grundmann, R; Jaeger, C; Kafka, A; Kreienberg, R; Sauer, G; Zeillinger, R, 2003)	0.51
"Digoxin solution was sprinkled directly over the surface of the duodenum using an endoscope, and its absorption rate was evaluated by serial monitoring of the serum concentration and by analysis of its initial 15-min increasing phase."	( MDR1 genotype-related duodenal absorption rate of digoxin in healthy Japanese subjects. Aoyama, N; Horinouchi, M; Kasuga, M; Kuroda, K; Miki, I; Morita, Y; Nakamura, T; Okumura, K; Sakaeda, T; Sakai, T; Shirasaka, D; Tamura, T; Yoshimura, K, 2003)	2.01
"Increased oral bioavailability and reduced nonglomerular renal clearance of digoxin both contribute to the interaction between digoxin and clarithromycin, probably due to inhibition of intestinal and renal P-glycoprotein."	( Contribution of increased oral bioavailability and reduced nonglomerular renal clearance of digoxin to the digoxin-clarithromycin interaction. Burhenne, J; Göggelmann, C; Haefeli, WE; Ludwig, J; Mikus, G; Rengelshausen, J; Riedel, KD; Walter-Sack, I; Weiss, J, 2003)	0.77
" Compared with water, grapefruit juice significantly reduced the digoxin absorption rate constant (3."	( Effects of grapefruit juice on intestinal P-glycoprotein: evaluation using digoxin in humans. Laizure, SC; Parker, RB; Soberman, JE; Yates, CR, 2003)	0.79
" Hence, infection and inflammatory diseases may impose variability in drug bioavailability through alterations in the intestinal expression and activity of drug transporters and metabolic enzymes."	( Suppression of drug-metabolizing enzymes and efflux transporters in the intestine of endotoxin-treated rats. Brocks, DR; Kalitsky-Szirtes, J; Piquette-Miller, M; Shayeganpour, A, 2004)	0.32
" Decreasing its expression could enhance the bioavailability of substrates as digoxin."	( Effect of recombinant interleukin-2 pretreatment on oral and intravenous digoxin pharmacokinetics and P-glycoprotein activity in mice. Ben Reguiga, M; Bonhomme-Faivre, L; Castagne, V; Farinotti, R; Gimenez, F; Soursac, M; Urien, S, 2004)	0.78
"Cisplatin-induced ARF differentially modulated the bioavailability and intestinal secretion of quinolones in rats."	( Effect of cisplatin-induced acute renal failure on bioavailability and intestinal secretion of quinolone antibacterial drugs in rats. Inui, K; Saito, H; Yamaguchi, H; Yano, I, 2004)	0.32
"It is known that digoxin, which is a liposoluble cardiac glycoside, is well absorbed from intestine."	( Intestinal absorption of digoxin and interaction with nimodipine in rats. Batu, O; Erol, K; Kilic, FS; Sirmagul, B; Yildirim, E, )	0.77
"Considering the narrow therapeutic index of digoxin and the low range between the safe and toxic serum concentrations of this drug, to evaluate the relative bioavailability of tablets and oral solution is necessary."	( Effects of 2-hydroxypropyl-beta-cyclodextrin on pharmacokinetics of digoxin in rabbits and humans. He, ZG; Li, YS; Tang, X; Zhang, RH; Zhang, TH; Zhao, C, 2004)	0.82
"The efflux transporter, P-glycoprotein (P-gp), located in the apical membranes of intestinal absorptive cells, can reduce the bioavailability of a wide range of orally administered drugs."	( Impact of excipients on the absorption of P-glycoprotein substrates in vitro and in vivo. Arellano, C; Cloarec, A; Cornaire, G; Hermann, P; Houin, G; Woodley, J, 2004)	0.32
" The area under the concentration-time course of Dx was significantly lower than that using Antiserum-II and the total body clearance values were significantly higher, while an obvious change of bioavailability was not observed."	( Pharmacokinetic interaction with digoxin and glucocorticoids in rats detected by radio-immunoassay using a novel specific antiserum. Fujii, Y; Higashi, Y; Ikeda, Y; Yamamoto, R; Yamashiro, M, 2005)	0.61
"This study was conducted to investigate in vivo the impact of interferon-alpha (IFN)-alpha on P-glycoprotein (P-gp) activity in rats by studying how its administration modifies the bioavailability of digoxin, a fairly pure P-gp substrate."	( Modification of the P-glycoprotein dependent pharmacokinetics of digoxin in rats by human recombinant interferon-alpha. Ben Reguiga, M; Bonhomme-Faivre, L; Farinotti, R; Orbach-Arbouys, S, 2005)	0.75
" Our previous studies demonstrated that sinomenine could significantly improve the bioavailability of paeoniflorin in rats, but the underlying mechanisms remain unknown."	( The effects of sinomenine on intestinal absorption of paeoniflorin by the everted rat gut sac model. Chan, K; Jiang, ZH; Liu, L; Liu, ZQ; Wong, YF; Xu, HX; Zhou, H, 2006)	0.33
" The bioavailability of digoxin after oral administration decreased significantly to 75."	( Effects of citronellal, a monoterpenoid in Zanthoxyli Fructus, on the intestinal absorption of digoxin in vitro and in vivo. Adachi, I; Kawakami, J; Kitazawa, H; Takagi, A; Yoshida, N, 2006)	0.86
"The significance of intestinal P-glycoprotein (P-gp) in determining the oral bioavailability of tacrolimus has been still controversial."	( Limited interaction between tacrolimus and P-glycoprotein in the rat small intestine. Achiwa, K; Aungst, BJ; Kobayashi, M; Oda, M; Saikachi, Y; Saitoh, H; Tadano, K; Takahashi, Y; Yamaguchi, M; Yuhki, Y, 2006)	0.33
" In particular, the oral bioavailability of these drugs may be influenced by the P-gp status of populations that rely heavily on hot chilli in their diets."	( Effects of capsaicin on P-gp function and expression in Caco-2 cells. Han, Y; Lim, LY; Tan, TM, 2006)	0.33
"On the basis of in vitro studies indicating that ursodeoxycholic acid (UDCA) is a cytochrome P450 (CYP) 3A4 inducer and a pregnane X receptor activator and because the pregnane X receptor is a transcriptional regulator of multidrug resistance 1 (MDR1)/P-glycoprotein (P-gp), we postulated that UDCA might decrease the bioavailability of CYP3A4 and P-gp probe drugs in humans."	( Effects of ursodeoxycholic acid on P-glycoprotein and cytochrome P450 3A4-dependent pharmacokinetics in humans. Becquemont, L; Burk, O; Drescher, S; Eichelbaum, M; Fromm, MF; Glaeser, H; Heinkele, G; Hitzl, M; Hofmann, U; Murdter, TE; Schaefer, C; Simon, N; Verstuyft, C, 2006)	0.33
" The objective of the present in vivo study was to investigate the effect of biliary depletion, as a method to mimic cholestasis, on the bioavailability and disposition of digoxin in biliary and pancreatic duct cannulated pigs."	( The effect of pancreatic and biliary depletion on the in vivo pharmacokinetics of digoxin in pigs. Erlwanger, K; Evilevitch, L; Lennernäs, H; Piedra, JV; Pierzynowski, S; Tannergren, C; Tatara, M; Weström, B, 2006)	0.75
"Poor permeation, p-gp-mediated efflux, and hydrolysis via a glucosidase contributed to the poor bioavailability of paeoniflorin."	( Mechanisms responsible for poor oral bioavailability of paeoniflorin: Role of intestinal disposition and interactions with sinomenine. Hu, M; Jiang, ZH; Liu, L; Liu, ZQ, 2006)	0.33
" Human oral bioavailability is an important pharmacokinetic property, which is directly related to the amount of drug available in the systemic circulation to exert pharmacological and therapeutic effects."	( Hologram QSAR model for the prediction of human oral bioavailability. Andricopulo, AD; Moda, TL; Montanari, CA, 2007)	0.34
" As a consequence, the oral bioavailability of THC and digoxin was higher in naturally P-gp-deficient mice."	( Disposition of Delta tetrahydrocannabinol in CF1 mice deficient in mdr1a P-glycoprotein. Abbara, C; Benyamina, A; Bonhomme-Faivre, L; Farinotti, R; Reynaud, M, 2008)	0.59
"The oral bioavailability of some therapeutic agents is markedly lower in cynomolgus monkeys than in humans."	( Species difference in intestinal absorption mechanism of etoposide and digoxin between cynomolgus monkey and rat. Amano, N; Fujita, H; Kato, Y; Kimura, Y; Kubo, Y; Nishimura, T; Ono, M; Tsuji, A, 2008)	0.58
"The bioavailability of etoposide was 12."	( Species difference in intestinal absorption mechanism of etoposide and digoxin between cynomolgus monkey and rat. Amano, N; Fujita, H; Kato, Y; Kimura, Y; Kubo, Y; Nishimura, T; Ono, M; Tsuji, A, 2008)	0.58
"Low bioavailability of etoposide in monkeys is due to poor intestinal uptake resulting from low influx from the apical side, rather than secretion via P-gp."	( Species difference in intestinal absorption mechanism of etoposide and digoxin between cynomolgus monkey and rat. Amano, N; Fujita, H; Kato, Y; Kimura, Y; Kubo, Y; Nishimura, T; Ono, M; Tsuji, A, 2008)	0.58
" Although the effects of Echinacea purpurea on systemic P-gp mediated drug transport are probably limited, an influence on drug bioavailability can not be excluded."	( Echinacea purpurea and P-glycoprotein drug transport in Caco-2 cells. Hansen, TS; Nilsen, OG, 2009)	0.35
" This suggests that, in contrast to the scenario suggested by in-vitro data, P-gp in the respiratory epithelium may have little influence on the disposition of drugs that are well absorbed from the lung."	( Lack of difference in pulmonary absorption of digoxin, a P-glycoprotein substrate, in mdr1a-deficient and mdr1a-competent mice. Forbes, B; Hutt, AJ; Johansson, F; Manford, F; Moore, V; Page, CP; Riffo-Vasquez, Y; Spina, D, 2008)	0.6
" In conclusion, berberine produced a dose-dependent increased bioavailability of digoxin and cyclosporine A by inhibition of intestinal P-gp."	( Effect of berberine on the pharmacokinetics of substrates of CYP3A and P-gp. Jiang, XH; Jin, JX; Ju, Y; Liu, CX; Qiu, W, 2009)	0.58
"Oral bioavailability (F) is a product of fraction absorbed (Fa), fraction escaping gut-wall elimination (Fg), and fraction escaping hepatic elimination (Fh)."	( Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination. Chang, G; El-Kattan, A; Miller, HR; Obach, RS; Rotter, C; Steyn, SJ; Troutman, MD; Varma, MV, 2010)	0.36
" These findings may explain the known interaction of telmisartan with digoxin and suggest that it may modulate the bioavailability of drugs whose absorption is restricted by P-gp and possibly also by BCRP or MRP2."	( Interaction of angiotensin receptor type 1 blockers with ATP-binding cassette transporters. Benndorf, RA; Böger, RH; Divac, N; Haefeli, WE; Herzog, M; Sauer, A; Schwedhelm, E; Weiss, J, 2010)	0.59
"25 mg DG in different SLNs and it was found that the relative bioavailability of DG in the SLNs was significantly increased compared with that of a DG solution."	( Improvement of digoxin oral absorption in rabbits by incorporation into solid lipid nanoparticles. Hu, L; Jia, H; Liu, C; Luo, Z; Xing, Q, 2010)	0.71
"P-glycoprotein is an efflux pump belonging to the ATP-binding cassette super-family that influences the bioavailability and disposition of many drugs."	( Tumor necrosis factor alpha increases P-glycoprotein expression in a BME-UV in vitro model of mammary epithelial cells. Al-Bataineh, MM; Gehring, R; Schultz, BD; van der Merwe, D, 2010)	0.36
"An increase in the area under the curve (AUC) after oral digoxin due to coadministration of drugs known as P-glycoprotein (P-gp) inhibitors has been reported in several studies, but there is very little information on the rate of absorption after P-gp inhibition."	( Modeling the kinetics of digoxin absorption: enhancement by P-glycoprotein inhibition. Sermsappasuk, P; Siegmund, W; Weiss, M, 2012)	0.93
"BBR increases bioavailability of DIG, which may be related to its inhibition effect on intestinal P-gp."	( [Effect of berberine on pharmacokinetics of digoxin after oral administration to rats]. Jiang, X; Ju, Y; Liu, C; Qiu, W, 2011)	0.63
" Tryptanthrin was well absorbed across the Caco-2 monolayers, and its transepithelial transports were dominated by passive diffusion."	( Transport characteristics of tryptanthrin and its inhibitory effect on P-gp and MRP2 in Caco-2 cells. Ma, G; Wang, H; Yan, J; Yang, Q; Zhang, X; Zhu, X, 2011)	0.37
" As a majority of discovery projects are focused on the development of orally bioavailable drugs, correlation of in vitro permeability data to in vivo absorption results is critical for understanding the structural-physicochemical relationship (SPR) of drugs exhibiting low levels of absorption."	( Optimization of the Caco-2 permeability assay to screen drug compounds for intestinal absorption and efflux. Press, B, 2011)	0.37
" Some recommendations may be unsuitable for use with high bioavailability tablets; some are accompanied by insufficient data relating to factors affecting both the response to digoxin and its handling by the body."	( Digoxin therapy: textbooks, theory and practice. Aronson, JK; Grahame-Smith, DG, 1976)	1.89
" In rats and dogs, [(14)C]GDC-0973 was well absorbed (fraction absorbed, 70-80%)."	( Preclinical disposition of GDC-0973 and prospective and retrospective analysis of human dose and efficacy predictions. Aoyama, RG; Belvin, M; Boggs, J; Choo, EF; Deng, Y; Hoeflich, KP; Johnston, SH; Kassees, R; Ly, J; Martini, JF; Merchant, M; Orr, C; Plise, E; Ramaiya, A; Robarge, K, 2012)	0.38
" These observations indicated that the three alkaloids may not only be P-gp inhibitors but also its substrates; they interact with each other and can potentially enhance their own bioavailability when taken concomitantly."	( Intestinal transport of pure diester-type alkaloids from an aconite extract across the Caco-2 cell monolayer model. Li, N; Liu, Z; Ma, J; Sui, Z; Tsao, R, 2012)	0.38
" The bioavailability of digoxin in LPS group was higher than that in the LPS + Cap group."	( Influence of capsaicin on fluctuation of digoxin pharmacokinetics in lipopolysaccharide-treated rats. Hayashi, T; Higashitani, A; Ijiri, Y; Irie, T; Kato, R; Kusukawa, Y; Nagata, M; Nakagawa, M; Tanaka, K; Urashima, Y; Yamamoto, Y, 2012)	0.95
" Epidemiological data show that the bioavailability of digoxin, a widely used agent for heart disease, varies among individuals."	( Intestinal microbiome and digoxin inactivation: meal plan for digoxin users? Large, PJ; Lu, L; Luo, X; Wu, Y; Zuo, L, 2014)	0.95
" In situ intestinal perfusion experiments also showed that CK, Ppd, and Ppt increased the absorption rate constant and permeability coefficient of rhodamine 123."	( Ginsenoside metabolites inhibit P-glycoprotein in vitro and in situ using three absorption models. Ge, G; Li, N; Liu, Y; Wang, D; Wang, X; Yang, L, 2014)	0.4
"Sodium diclofenac (Na-DFC) and celecoxib (CLXB) are common nonsteroidal anti-inflammatory (NSAID) drugs which suffer from poor bioavailability and severe side effects when consumed orally, and their transdermal delivery might present important advantages."	( HIV-TAT enhances the transdermal delivery of NSAID drugs from liquid crystalline mesophases. Aserin, A; Cohen-Avrahami, M; Garti, N; Ottaviani, MF; Shames, AI, 2014)	0.4
" Moreover, pharmacokinetic studies were performed in animal models to evaluate the absolute bioavailability of oral doses (Foral) of different compounds."	( Development, validation, and application of a novel 7-day Caco-2 cell culture system. Bi, H; Cai, Y; Chen, P; Hu, J; Hu, R; Huang, M; Xu, C, )	0.13
" Furthermore, pharmacokinetic studies of several compounds performed in animal models revealed that the absolute bioavailability of oral doses in vivo was well correlated with the Caco-2 permeability in vitro."	( Development, validation, and application of a novel 7-day Caco-2 cell culture system. Bi, H; Cai, Y; Chen, P; Hu, J; Hu, R; Huang, M; Xu, C, )	0.13
" Digoxin load based on ingested dose will generally overestimate digoxin-Fab doses as bioavailability is 60-80%, and further reduced by vomiting and activated charcoal."	( Digoxin-specific antibody fragments in the treatment of digoxin toxicity. Buckley, NA; Chan, BS, )	2.48
" In summary, trantinterol is a potent noncompetitive P-gp inhibitor which may increase the bioavailability of other P-gp substrate drugs coadministered with it."	( Trantinterol, a novel β2-adrenoceptor agonist, noncompetitively inhibits P-glycoprotein function in vitro and in vivo. Fan, H; Fawcett, JP; Gu, J; Guo, Y; Liu, J; Ma, W; Sun, Y; Wang, T; Yang, J; Yang, Y; Yang, Z, 2015)	0.42
" Thus, their bioavailability could be affected by changes in this transporter."	( Fructose-induced metabolic syndrome decreases protein expression and activity of intestinal P-glycoprotein. Celuch, SM; Ghanem, CI; Godoy, YC; Martinez, SA; Novak, A, 2015)	0.42
"The present study demonstrated that MetS-like conditions generated by enhanced fructose intake in rats decreased the protein expression and activity of ileal P-gp, thus increasing the bioavailability of P-gp substrates."	( Fructose-induced metabolic syndrome decreases protein expression and activity of intestinal P-glycoprotein. Celuch, SM; Ghanem, CI; Godoy, YC; Martinez, SA; Novak, A, 2015)	0.42
"The ATP-binding cassette B1 (ABCB1) gene encodes P-glycoprotein, a transport protein, which plays an important role in the bioavailability of digoxin."	( ABCB1 gene variants, digoxin and risk of sudden cardiac death in a general population. Aarnoudse, AL; Deckers, JW; Eijgelsheim, M; Franco, OH; Hofman, A; Niemeijer, MN; Rijnbeek, PR; Stricker, BH; Uitterlinden, AG; van den Berg, ME, 2015)	0.94
" Notably, compound 85 demonstrated a reasonable antiproliferation effect on MV4;11 leukemia cells and exhibited a good pharmacokinetic profile with high oral bioavailability (75."	( Discovery of Benzo[cd]indol-2(1H)-ones as Potent and Specific BET Bromodomain Inhibitors: Structure-Based Virtual Screening, Optimization, and Biological Evaluation. Ding, K; Liu, Z; Song, M; Tu, Z; Wang, Z; Xiang, Q; Xing, Y; Xu, Y; Xue, X; Zhang, Y; Zhou, Y, 2016)	0.43
"Purple grape juice can increase the bioavailability of orally administered digoxin, especially with multiple doses."	( Effect of purple grape juice on the pharmacokinetics of digoxin: Results of a food-drug interaction study . Ju, Y; Qiu, W; Song, X; Zhao, H, 2019)	0.99
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."	( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019)	0.51
" The simulations suggest that for highly soluble drugs, such as verapamil, the predicted bioavailability was comparable pre- and post-RYGBS."	( PBPK modeling of CYP3A and P-gp substrates to predict drug-drug interactions in patients undergoing Roux-en-Y gastric bypass surgery. Chan, LN; Chen, KF; Lin, YS, 2020)	0.56
" Carriers of CGC/CGT and TTT/TTT had 35% higher apparent bioavailability compared to the reference group CGC/CGC, while no difference was seen in CGC/TTT carriers."	( Combinations of common SNPs of the transporter gene ABCB1 influence apparent bioavailability, but not renal elimination of oral digoxin. Fuhr, U; Gazzaz, M; Hsin, CH; Schaeffeler, E; Schwab, M; Stoffel, MS; Taubert, M, 2020)	0.76
"2%, while extent of oral bioavailability fell by 55."	( Changes in digoxin pharmacokinetics associated with hepatic P-glycoprotein upregulation in rats with non-alcoholic fatty liver disease. Jeong, HJ; Kang, HE; Lee, SH, 2021)	1.01
"The ATP-binding cassette transporter P-glycoprotein (P-gp) limits the oral bioavailability of many drugs."	( Characterization of P-glycoprotein orthologs from human, sheep, pig, dog, and cat. Azimi, M; Brett, CM; Giacomini, CP; Giacomini, KM; Riselli, A; Silva, DB; Yee, SW, 2023)	0.91

Dosage Studied

Digoxin monitoring was examined according to 13 criteria in two nursing homes. Plasma concentrations of digoxin after multiple administration at varying dosing schedules in Korean patients were used for population modeling.

Excerpt	Relevance	Reference
"Although oral drug bioinequivalence has been attributed to a number of causes (excipients, dosage form, variation in dissolution time, and aging) less is known about bioavailability problems of topical medications in ophthalmology."	( Bioavailability and generic prescribing. Mindel, JS, )	0.13
"Outpatient prescriptions dispensed to 17,000 individuals in the county of Jämtland, Sweden, have been analyzed with regard to doses and dosage schedules."	( Doses and dosage intervals of drugs--clinical practice and pharmacokinetic principles. Boëthius, G; Sjöqvist, F, 1978)	0.26
" The relationship of propranolol dosage to blood levels, the effect of blood levels on pharmacological response, the metabolism and elimination of propranolol, and determination of rational dosage of the drug, are discussed."	( Pharmacokinetics in drug therapy. I: Propranolol hydrochloride as adjunct therapy in the treatment of thyrotoxicosis. Robayo, JR, 1976)	0.26
" This results in a raised serum concentration of cardiac glycosides unless the dosage is decreased considerably."	( [Significance of serum digoxin concentration and its influencing factors]. Erdmann, E; Krawietz, W; Vogt, W, 1976)	0.57
" Advanced age modifies the approach to treatment; the choice of drugs and the dosage must be adjusted accordingly."	( Drug therapy for cardiovascular disease in the aged. Kennedy, RD, 1975)	0.25
" Correlation between digoxin dosage and serum level was weak and unaffected by blood urea level."	( Serum digoxin levels in neonates, infants and children with heart disease. Hurley, PJ; Neutze, JM; Rutherford, JD, 1977)	1.06
" There was no significant difference in SVT with the two digitalization dosage levels (31."	( Supraventricular tachyarrhythmias after myocardial revascularization: a randomized trial of prophylactic digitalization. Barner, HB; Codd, JE; Kaiser, GC; Stothert, JC; Tyras, DH; Willman, VL, 1979)	0.26
" Dosage regimens based on the measurement of creatinine-clearance are of little help in "effective digitalisation"."	( Digitalis pharmacokinetics and therapy with respect to impaired renal function. Kramer, P, 1977)	0.26
" Exact prediction of serum digoxin concentrations by various dosage calculations has not succeeded."	( Clinical pharmacokinetics of digoxin. Iisalo, E, )	0.72
" The reasons for this difference in dosage are not clear."	( Clinical pharmacokinetics of digoxin in infants. Andersson, KE; Wettrell, G, )	0.42
"In a prospective study 73 patients on maintenance digitalis treatment at the Paracelsus Institute, Bad Hall, were clinically examined and the dosage of the drug was adjusted according to cardiac symptoms."	( [Digitalis therapy in practice: correlation between clinical evaluation and plasma digoxin concentration (author's transl)]. Bonelli, J; Kaik, G; Magometschnigg, D; Rameis, H, 1979)	0.48
" Twenty-seven percent of the admissions could have been avoided by a more careful choice and dosage of drug."	( Hospital admissions due to adverse drug reactions. Eliakim, M; Levy, M; Lipshitz, M, )	0.13
"In pediatrics it is difficult to define indications of drug therapy, appropriate dosage and therapeutic reliability of drugs because experimental pharmacology in this age group has many obstacles."	( [Conditions for rational drug treatment in childhood (author's transl)]. von Harnack, GA, 1979)	0.26
" Frusemide dosage was increased and the alpha adrenoreceptor blocking drug prazosin hydrochloride was added to the therapeutic regime."	( The use of alpha blockade in the treatment of congestive heart failure associated with dirofilariasis and mitral valvular incompetence. Atwell, RB, 1979)	0.26
"Often drug dosage may be chosen rationally by use of plasma concentration (CP) as the "therapeutic" end point."	( Forecasting individual pharmacokinetics. Beal, S; Marathe, VV; Rosenberg, B; Sheiner, LB, 1979)	0.26
" The present paper deals with the development of a solid dosage form (tablets) using a physical association of gitoxin and sodium escinate."	( Bioavailability study of gitoxin in a solid dosage form. de Suray, JM; Dodion, L; Hupin, C; Lesne, M; Lorent, M; Versluys, J, 1979)	0.26
" Raising quinidine dosage to 1000 mg daily caused no further digoxin clearance reduction."	( [Interaction of quinidine and digoxin in humans (author's transl)]. Grabensee, B; Peters, U; Risler, T; Seipel, L, 1979)	0.79
" The relatively small dosage requirement for medigoxin was attributed partly to a lower clearance rate and partly to more nearly complete absorption."	( Comparison of medigoxin and digoxin in the control of atrial fibrillation. Coburn, P; Kongola, GM; Mawer, GE, 1979)	0.86
" Enzyme induction in connection with low phenytoin dosage and inhibition by high dosage is the suggested mechanism."	( The effect of phenytoin on the tissue concentrations of digoxin in the rat. Allonen, H, 1977)	0.5
"Current practice with digoxin was assessed in a group of 42 elderly patients by comparing plasma digoxin concentrations attained on previously established maintenance doses with those generated by a computer programme designed to calculate dosage schedules to suit individual patients."	( Computer-assisted review of digoxin therapy in the elderly. Goldberg, A; Sumner, DJ; Wandless, I; Whiting, B, 1978)	0.87
" Variations in bioavailability and intestinal absorption are important factors in the determination of dosage and should be reduced to a minimum by improved pharmaceutical formulations."	( Digoxin therapy: a clinical pharmacokinetic approach. Whiting, B, 1978)	1.7
" Following dosage by either route, significantly more radioactivity was recovered from animals with nearly intact enterohepatic circulation."	( Assessment of enterohepatic circulation of 3H-digoxin with a minimal interruption technique. Caldwell, JH; Kakumoto, Y; Thomford, NR, 1978)	0.52
" Using a radioimmunoassay (RIA) technique, serial plasma levels were recorded for 8 h following a single oral dose in five fasting volunteer subjects, and urinary glycoside elimination was measured for 4 consecutive days after dosage by use of a modification of the RIA method."	( Comparison of digoxin and medigoxin in normal subjects. Greenwood, H; Hamer, J; Hayward, RP, 1978)	0.62
" The findings showed that the serum digoxin level was not correlated with the dosage of digoxin nor the patient's clinical state of digitalization."	( Serum digoxin levels in elderly nursing home patients: appraisal of routine periodic measurements. Dimant, J; Merrit, W, 1978)	1.01
" The study was designed to measure the incidence of digoxin toxicity, evaluate monitoring practices for digoxin use and evaluate the adequacy of digoxin dosing patterns."	( Multidisciplinary audit of digoxin. DeSantis, D; Duffy, MG; Keys, PW, 1978)	0.81
" Near maximal capacity for the tubular secretion of digoxin was found when normal digoxin dosage was used."	( Spironolactone-induced changes in digoxin kinetics. Andersen, JD; Heebøll-Nielsen, N; Moltke, E; Nielsen, OG; Steiness, E; Sørensen, U; Waldorff, S, 1978)	0.79
" Non-compliance with prescribed digoxin dosage occurred, therefore, in 46% of the patients studied."	( Digoxin compliance in patients from general practice. Johnston, GD; McDevitt, DG, 1978)	1.98
" Charts were compared with established criteria to determine whether the assay was indicated and performed correctly and whether dosage was adjusted correctly based on assay results."	( Appropriateness of the use of serum digoxin and digitoxin assays. Schneider, PJ; Slaughter, RL; Visconti, JA, 1978)	0.53
" After a dosing period equal to at least five half-lives, three to four consecutive daily digoxin plasma concentrations were determined."	( Relationship between plasma concentration and dose of digoxin in patients with and without renal impairment. Graves, PE; Hager, WD; Marcus, FI; Mayersohn, M; Okada, RD; Perrier, DG, 1978)	0.73
"Digoxin dosage regimens for patients on chronic intermittent hemodialysis (CIH) were calculated from pharmacokinetic data of digoxin in these patients between the during hemodialyses."	( Pharmacokinetic aspects of digoxin in patients with terminal renal failure. IV. Clinical implications of own observations with a recent review of literature. Oe, PL; van der Vijgh, WJ, 1978)	2
" It is concluded that pharmacist intervention may have had an effect in reducing digoxin dosage and toxicity."	( Pharmacist's effect on digoxin usage and toxicity. Cooper, JW; Lewis, KP; McKercher, PL, 1976)	0.79
"Computer programs for drug dosage adjustment may be fixed, adaptive or empirical."	( Computer assisted prescribing of drugs. Mawer, GE, 1976)	0.26
" By these mechanisms, cardiac failure potentially affects absorption and disposition characteristics of drugs, which may necessitate adjustment in dosage regimen for optimum therapy."	( Pharmacokinetics in patients with cardiac failure. Benowitz, NL; Meister, W, )	0.13
" The factors of uncertainty for efficient therapy -- unknown rates of resorption and elimination, mistakes in dosage by patients and interaction with other medicaments on account of the multimorbidity of old age -- demand a better control than only clinical observation and electrocardiography."	( [Serum glycoside level in old age. Problems of course control in glycoside therapy]. Schwarzfischer, VP, 1976)	0.26
"70 ng/ml) can be obtained reliably if the dosage of digoxin and its derivatives is based on the body weight."	( [The importance of body weight in treatment with digoxin and digoxin derivatives (author's transl)]. Ruiz-Torres, A; Schneider, J, 1977)	0.76
" Literature reports on the oral bioavailability of solutions and solid dosage forms of digoxin were critically reviewed, but no reliable comparison of the extent and reproducibility of oral absorption of cardioactive agents from administered digoxin or beta-methyldigoxin could be made from the widely variable digoxin studies with nonspecific assays."	( Pharmacokinetics of beta-methyldigoxin in healthy humans II: Oral studies and bioavailability. Garrett, ER; Hinderling, PH; Wester, RC, 1977)	0.77
" These data explain (in part) the larger digoxin dosage requirement of infants."	( Renal clearance of digoxin in young infants. Gorodischer, R; Jusko, WJ; Yaffe, SJ, 1977)	0.85
" The relative peak heights and area under the ejection time-time curves indicated a linear dose-response relationship on intravenous administration and an effect greater than that reported for larger amounts of digoxin."	( Pharmacokinetics of beta-methyldigoxin in healthy humans III: Pharmacodynamic correlations. Garrett, ER; Hinderling, PH, 1977)	0.73
" The newborn group showed in all three phases serum digoxin levels significantly higher than those found in the other groups, in spite of an only slightly higher dosage of digoxin used in comparison to the other groups."	( [Serum digoxin levels in the pediatric age (author's transl)]. Del Torso, S; Pellegrino, PA; Stefanelli, U, 1977)	0.96
" In comparison wtih the large variations in individual dosage of digoxin and beta-methyl-digoxin, this difference is too small to be of practical importance."	( Serum glycoside concentrations after single or repeated intravenous doses of beta-methyl-digoxin and digoxin. Marinow, J; Olcay, A; Schaumann, W; Weiss, W, 1977)	0.72
" By knowing the elimination rate constant the extent to which a cardiac glycoside would accumulate in the body following a fixed dosing regimen can be calculated."	( [Pharmacokinetics of cardiac glycosides and clinical consequences]. Kuhlmann, J; Rietbrock, N; Vöhringer, HF, 1977)	0.26
"0 ng/ml showed close resemblance to patients with no cardiac evidence of toxicity with regard to: mean age, kidney function, mean digoxin dosage and mean body weight."	( [Digitalis intoxication: specifity and significance of cardiac and extracardiac symptoms. part I: Patients with digitalis-induced arrhythmias (author's transl)]. Doering, W; König, E; Sturm, W, 1977)	0.46
"0 ng/ml) the patients with and without extracardiac signs of digitalis toxicity are compared with each other in regard to: mean body height and weight, concentration of digoxin, potassium and creatinine, digoxin dosage and mean age."	( [Digitalis intoxication: specifity and significance of cardiac and extracardiac symptoms. part II. Patients with extracardiac symptoms of digitalis intoxications (author's transl)]. Doering, W; König, E; Sturm, W, 1977)	0.45
" 3 Approximately 10% less digoxin was recovered in urine collected in a 12 h dosage interval during the lower dosage administration of capsules."	( The comparability of dosage regimens of Lanoxin tablets and Lanoxicaps. French, J; Johnson, BF; Smith, G, 1977)	0.56
" In 6 patients renal excretion of digoxin was clearly less than in normal subjects during chronic dosing of the same digoxin preparation."	( [Intestinal absorption of digoxin in systemic sclerosis (author's transl)]. Brachtel, R; Gilfrich, HJ, 1977)	0.84
" These results indicate that acute digitalisation at the stated dosage in general has an effect on abnormal myocardial function only if there is no additional coronary heart disease."	( [Early digitalisation of patients with arterial hypertension (author's transl)]. Eversmann, A; König, E; Lehnert, J; Nechwatal, W, 1977)	0.26
" In the latter group the daily dosage reported by the patients failed to correlate with the plasma-digoxin concentration by radioimmunoassay."	( [Plasma-digoxin concentration in patients at time of hospital admission (author's transl)]. Lichey, J; Rietbrock, N; Schröder, R, 1977)	0.91
" Thus, beta-acetyldigoxine combined with antacids of the aluminum hydroxide and magnesium hydroxide type can be applied in the same dosage as usual since no decrease of effect has to be apprehended."	( The bio-availability of beta-acetyldigoxine alone and combined with aluminum hydroxide and magnesium hydroxide (Alucol). Bonelli, J; Hitzenberger, G; Hruby, K; Kaik, G; Magometschnigg, D, 1977)	0.87
" Age-related differences in inotropic and arrhythmogenic effects of digoxin exist exist and are related to differences in drug response rather than drug kinetics; this provides experimental support for the different dosage responses."	( Differential effects of digoxin at comparable concentrations in tissues of fetal and adult sheep. Berman, W; Heymann, MA; Melmon, KL; Ravenscroft, PJ; Rudolph, AM; Sheiner, LB, 1977)	0.8
" It can be concluded that echocardiography is a feasible tool in determining changes of left ventricular dynamics during administration of vasoactive drugs, in indicating the individual dosage of a vasoactive drug in each patient and the follow-up the course of the therapeutic success."	( [Echocardiographic evaluation of left ventricular function during therapy with cardiovascularly effective drugs]. Stefan, G, 1976)	0.26
" There was variation in tracer binding when serum from dogs dosed with thyrotropin was assayed with the first tracer, but there was little variation with the second."	( Reduced variation of tracer binding in digoxin radioimmunoassay by use of (125I)-labeled tyrosine-methyl-ester derivative: relation of thyroxine concentration to binding. Kroening, BH; Weintraub, M, 1976)	0.52
"The concentration of digitalis glycosides in serum may serve as a useful guide in adjusting digitalis glycoside dosage to individual needs."	( [Serum concentration of digitalis glycosides as a therapeutic guide]. Paumgartner, G, 1976)	0.26
" This model is an useful concept because it can explain the necessity to vary Digoxin dosage in patients with different body weights, the time course of the effect of Digoxin and certain causes of increased tolerance to Digoxin."	( A two compartment open model for digoxin pharmacokinetics in patients receiving a wide range of digoxin doses. Grupp, G; Rabkin, SW, 1975)	0.76
" Computer programmes to relate steady state plasma concentration to oral digoxin dosage take no account of absorptive capacity, are limited to gross approximations, and cannot replace determination of plasma concentration to assess the degree of digitalization."	( Maximal intestinal absorption of digoxin, and its relation to steady state plasma concentration. Bye, C; Johnson, BF, 1975)	0.77
" The use of these assay methods has supplemented earlier studies with radiolabeled digitalis preparations and has made it possible to obtain much new information concerning factors which may contribute to the well known patient to patient variability in digitalis dosage requirements and in sensitivity to the toxic effects of cardiac glycosides."	( Serum digitalis measurements in the assessment of digitalis resistance and sensitivity. Butler, VP; Lindenbaum, J, 1975)	0.25
" In that way of dose-response curves for the rapid effects of ouabain and other inhibitors of active Na transport were obtained with both the original, ouabain-sensitive (OS) and the variant, ouabain-resistant (OR) cells."	( Variant HeLa cells selected for their resistance to ouabain. Rosenberg, HM, 1975)	0.25
"The absorption of digoxin in cystic fibrosis was evaluated in 16 subjects by assessing the relationship between dosage expressed in mug/kg/day and serum digoxin concentration."	( Absorption of digoxin in children with cystic fibrosis. Crudup, C; Dooley, RR; Finkelstein, S; Moss, AJ; Osher, AB; Young, GA, 1975)	0.95
"A dose-response relation between cardiac glycosides and systolic time intervals has previously been established in short-term studies in which the glycoside was administered intravenously in these studies there was uncertainty regarding the steady state kinetics, and maintenance of the early serum levels would have resulted in toxicity."	( Dose-response relation between therapeutic levels of serum digoxin and systolic time intervals. Cuddy, TE; Hoeschen, RJ, 1975)	0.5
" However, in view of the possible predisposition of such patients to toxicity, lower serum levels than were achieved in many of our patients seem desirable and a modified dosage schedule is suggested."	( Treatment with digoxin and measurement of serum digoxin levels after myocardial infarction. McL White, B; Norris, RM; Sharpe, DN, 1975)	0.61
" Collaborators were supplied with 3 composites of tablets of different dosage levels."	( Collaborative study of a semiautomated colorimetric analysis of digoxin tablets. Juhl, WE, 1975)	0.49
" Fairly good correlations have been noted between different dosage schedules and various rhythm disturbances."	( Radioimmunoassay of serum digoxin in relation to digoxin intoxication. Dube, DP; Katiyar, BC; Rai, AN; Singh, RB; Somani, PN; Srivastav, DK, 1975)	0.55
" This variability is a major limiting factor in the use of dosage regimen nomograms that assume a constant V-ss-D and a rigorous relationship between t1/2beta and creatinine clearance (Cl-CR)."	( Digoxin pharmacokinetics: role of renal failure in dosage regimen design. Elwood, CM; Jusko, WJ; Kohli, RK; Koup, JR, 1975)	1.7
" Two hours after dosing during the slow excretion phase confirmed by serial serum sampling, the animals were killed."	( Altered tissue digoxin uptake after a toxic dose. Shapiro, W; Taubert, K, 1975)	0.61
" Digoxin intoxication was found to develop in cases of its content exceeding the mean level for the given dosage (4 patients), however, in 2 patients signs of intoxication developed with a low concentration of Digoxin."	( [Treatment of circulatory insufficiency in patients with ischemic heart disease with digoxin and determination of its concentration in the blood serum by radioisotope method]. Cherniak, MS; Dobrotvorskaia, TE; Grishutina, KA; Smetnev, AS; Zubovskiĭ, GA, 1975)	1.39
" It permits early detection of digitalis intoxication in the absence of marked clinical and ECG evidence, and adjustment of dosage accordingly."	( [Proceedings: Clinical value of serum digoxin and digitoxin determination in renal insufficiency]. Ferrini, B; Klauser, H; Klauser-Reucker, C; Moccetti, T, 1975)	0.53
" Since a time duration of drug presence at the site of action is vital for the cure of disease, a comprehensive and quantitative expression of these time courses of drug distribution as a function of dose and route of administration is necessary for the establishment of proper dosage regimens for the treatment of disease and the avoidance of toxicities."	( [Clinical pharmacokinetics]. Balant, L; Garrett, ER; Revillard, C, 1976)	0.26
" 4 There was no correlation between plasma levels of digoxin and the tendency to dysrhythmia, since peak plasma concentrations of digoxin were reached at about 60 min after dosing whereas maximal sensitivity to acetylstrophanthidin was found 3 to 6 h after administration of digoxin."	( The relationship between cardiotoxicity and plasma digoxin concentration in conscious dogs. Chapple, DJ; Hughes, R; Johnson, BF, 1976)	0.76
" Cibenzoline was given for 4 weeks at a dose of 130 mg twice daily in patients aged less than 70 years (group I, n = 15) and this dosage was reduced by half in patients over 70 years of age (group II, n = 7)."	( [Combination of oral administration of cibenzoline and digoxin in patients with supraventricular arrhythmia]. Arnaud, R; Bine-Scheck, F; Garnier, LF; Pruvost, P; Wanszelbaum, H, 1992)	0.53
"Routine clinical pharmacokinetic data collected from patients receiving digoxin have been analysed to evaluate the role of patient characteristics for estimating dosing regimens."	( Digoxin population pharmacokinetics from routine clinical data: role of patient characteristics for estimating dosing regimens. Aoyama, T; Higuchi, S; Mine, H; Yukawa, E, 1992)	1.96
"Differences in bioavailability of many drugs from their various dosage forms have been shown to be relatively common in human medicine."	( Bioavailability and bioinequivalence of drug formulations in small animals. Watson, AD, 1992)	0.28
" It is demonstrated that an statistically significant pharmacokinetic interaction was found only after multiple dosing under conditions of steady-state, whereas after single dosing no interaction was observed."	( The importance of prospective planning of pharmacokinetic trials. Considerations of studies on the phenytoin-digoxin-(P-D) and phenytoin-digitoxin-(P-DT) interaction. Rameis, H, 1992)	0.5
"In spite of being a widely-used drug, the dosage of Digoxin is not adequately worked out and compliance is a long way from the optimum."	( [The use of digoxin in primary care]. Arnau, JM; Artaza, MA; Mundet, X; Vidal, X, 1992)	0.91
" The mean digoxin dosage at the development of fatal arrhythmias after the 100 micrograms/kg of FK 33,824 was 30% lower than the control group."	( Opioid receptor agonists D-Ala-2-Me-Phe-4-Met-(O)-ol enkephalin and ethylketocyclazocine in the brain accentuate digoxin-induced arrhythmias. Rabkin, SW, )	0.74
" It covers the various approaches to digoxin therapeutics including the therapeutic endpoint and the use of plasma concentrations of digoxin, the various problems involved in dosage design (particularly pharmacokinetic variability), prescribing aids (and their total impact on the variability in plasma concentrations achieved), and finally, the alternative use of blood-level data to separate and identify the variation in absorption-disposition from the variation in the relationship of plasma concentration to effect."	( Digoxin therapeutics: straightening out the facts. Doi, SA, 1992)	2
" These better estimates should result in improved initial dosage of digoxin."	( Pharmacokinetics of the digoxin-quinidine interaction via mixed-effect modelling. Kamigaki, M; Lane, J; Mergener, MA; Murray, W; Williams, PJ, 1992)	0.83
" It is these data which have also produced the current age-specific dosing guidelines for the therapeutic administration of digoxin in various paediatric subpopulations."	( Age-related differences in digoxin toxicity and its treatment. Kearns, GL; Wells, TG; Young, RA, )	0.64
" By defining the mathematical relation between STI and simultaneous serum digoxin concentrations following intravenous administration of 1 mg digoxin, computer simulations can be made of the effect of dosing changes on blood and tissue concentrations."	( Clinical use of serum digoxin concentrations. Lewis, RP, 1992)	0.83
" The main problems in this case were regulation of the dosage and acquiring the necessary amount of antidote which greatly exceeded the hospital's own depot."	( [Severe digitalis poisoning after the ingestion of 1 g of digoxin]. Bodmann, KF; Schuster, HP; Tröster, S, 1992)	0.53
" Thus, modification in the dosage regimen of digoxin may be unnecessary in the case of coadministration with captopril."	( The effect of captopril on pharmacokinetics of digoxin in patients with mild congestive heart failure. Ishii, M; Kobayashi, K; Miyakawa, T; Shionoiri, H; Takasaki, I, 1991)	0.8
"9 kg and dosage 2-4 mg/kg/24 hrs given in two equal doses, 12 hourly."	( Efficacy and safety of oral sotalol in early infancy. Sandor, G; Tipple, M, 1991)	0.28
" In the presence of Org 10172 there was a reduction in the AUC of digoxin during one dosing interval after the seventh digoxin tablet from 20 to 17 ng."	( Interaction of ORG 10172, a low molecular weight heparinoid, and digoxin in healthy volunteers. Breimer, DD; Danhof, M; de Boer, A; Moolenaar, AJ; Stiekema, JC, 1991)	0.76
" Six patients with digoxin levels over therapeutic range and signs of digitalis toxicity had coincidental acute renal failure, which in 4 cases was subclinical--in 2 of these late it was pre-renal- and, in spite of this, all were inadvertently given the usual dosage of beta methyl digoxin."	( [Serum digoxin in children treated with beta methyl digoxin]. Eimbcke, F; Enríquez, G; García, Y; Jaeger, H; Soler, P; Vicuña, D; Zilleruelo, R, )	0.91
" Dosage of spirapril was increased from 12 mg to 48 mg once daily."	( Digoxin pharmacokinetics and spirapril, a new ace inhibitor. Flemming, J; Johnson, BF; Johnson, J; Wilson, J, 1991)	1.72
" There was no relation between the digoxin plasma level and the dosage schedule, the ECG findings, the renal function, the use of other drugs or the anthropometric data."	( [Evaluation of the use of digoxin in a primary care emergency service]. Campodarve, I; Ibáñez, J; Knobel, H; Nogués, J; Ortiz, P; Serrat, R, 1991)	0.86
" At the dosage used side effects related to flecainide or digoxin were not observed."	( Prevention of arrhythmias after noncardiac thoracic operations: flecainide versus digoxin. Biollaz, J; Borgeat, A; Cavin, R; Munafo, A; Petropoulos, P; Schwander, D, 1991)	0.75
" greater than 1 year), presence of digoxin treatment, or the dosing schedule employed."	( A large-scale trial of captopril for mild to moderate heart failure in the primary care setting. DiBianco, R, 1991)	0.56
" To reduce the number of samples drawn too soon after a previous dose and in an effort to improve digoxin TDM at this teaching hospital, a new dosing and monitoring policy was initiated."	( Making digoxin therapeutic drug monitoring more effective. Matzuk, MM; Shaw, LM; Shlomchik, M, 1991)	0.95
" For these fractions dose-response curves for 86Rb uptake and for displacement of digoxin were parallel, respectively, to those of ouabain and digoxin, suggesting similarities of digoxin-like immunoreactive substance to cardiac glycosides."	( Partial purification of endogenous digitalis-like compound(s) in cord blood. Balzan, S; Biver, P; Gazzetti, P; Ghione, S; Montali, U, 1991)	0.51
" Most patients were greater than or equal to 70 years old and developed toxicity during maintenance dosing with digoxin."	( Digoxin Immune Fab therapy in the management of digitalis intoxication: safety and efficacy results of an observational surveillance study. Carpenter, VP; Furberg, CD; Hickey, AR; Hlatky, MA; Kirkpatrick, CH; Smith, TW; Strauss, HC; Tilson, HH; Wenger, TL, 1991)	1.94
" From the investigations to date, changing the digoxin dosage prior to initiating calcium antagonist therapy is, however, not justifiable."	( [Interaction between calcium antagonists and digoxin]. Christensen, C, 1991)	0.8
" In the next stage of the therapy they additionally received a 200 mg intravenous dosage of pentoxifylline and continued to take pentoxifylline orally for the period of at least 14 days."	( [The effect of combined treatment in chronic congestive heart failure with digoxin, furosemide and pentoxifylline upon blood viscosity]. Kochmański, M; Zochowski, RJ, 1990)	0.51
"The dixogin dosage with an interruption of two consecutive days a week is frequently used in our country."	( [The use of digitalis: a prospective study on the posology of digoxin with weekly interruption]. Castro Beirás, A; Cuña Estévez, B; Soto Pedre, E, )	0.37
" Where digoxin was required dosage increases were necessary to achieve optimum clinical control."	( Supervised withdrawal of long-term digoxin therapy. Fair, JF, 1990)	1.01
"min-1) in pretreated groups was performed 7 d after digoxin dosing was stopped, when plasma digoxin concentrations were zero."	( Increased sensitivity to isoprenaline following digoxin pretreatment in anaesthetised and conscious dogs. Einstein, R; Gray, P; Hunyor, SN; Jones, MP; Mihailidou, AS; Richardson, DP, 1990)	0.79
" The patients were continuously treated with verapamil for two periods of two weeks at two dosage levels, 120 mg/d and 240 mg/d, whereafter verapamil was withdrawn."	( Verapamil-digoxin interaction in chronic hemodialysis patients. Halck, S; Johannessen, AC; Klitgaard, NA; Rendtorff, C, 1990)	0.68
" The steady-state serum concentrations of digoxin and digitoxin can be affected if the changes in absorption are of sufficient magnitude, and adjustments in digoxin or digitoxin dosage may be required."	( Current status of cardiac glycoside drug interactions. Hooymans, PM; Merkus, FW, )	0.4
" Nitrendipine in the dosage of 10 mg once daily caused a small, insignificant tendency to elevate digoxin plasma levels."	( Nitrendipine/digoxin interaction. Heidemann, H; Kirch, W; Logemann, C; Ohnhaus, EE; Santos, SR, 1987)	0.86
" Dosing schedules based on milligrams per square meter body surface area correlated better with plasma flecainide levels than did dosing based on milligrams per kilogram body weight."	( Flecainide acetate for resistant arrhythmias in the young: efficacy and pharmacokinetics. Fredell, P; Garson, A; Gothing, C; McQuinn, RL; Perry, JC; Smith, RT, 1989)	0.28
" With chronic oral dosing of amlodipine once daily for 14 days, support was provided for the linearity of amlodipine's pharmacokinetics and absence of such with chronic oral dosing with verapamil, diltiazem, and nifedipine."	( The pharmacokinetic profile of amlodipine. Abernethy, DR, 1989)	0.28
" those with a CI greater than the median value, were characterized by a lower daily dose and dosage frequency."	( Serum digoxin and beta-methyldigoxin in elderly patients on hospital admission: correlation with home compliance and clinical variables. Bartolomei, GC; De Giorgio, LA; Franconi, F; Gironi, A; Innocenti, F; Mian, M; Seghieri, G, 1989)	0.76
"In 43 ICU patients undergoing continuous volume constant hemofiltration (CVHF), the pharmacokinetics of 12 drugs were investigated to ensure correct dosage adjustments."	( [Dosage adjustment of drugs during continuous hemofiltration. Results and practical consequences of a prospective clinical study]. Dehne, M; el Abed, K; Hofmann, W; Kroh, U; Lennartz, H, 1989)	0.28
" Captopril improved functional class (Canadian Cardiovascular Society) and reduced requirements for increased diuretic dosage at both 1 and 3 months of maintenance treatment."	( Comparison of the immediate and long-term effects of captopril and isosorbide dinitrate as adjunctive treatment in mild heart failure. Barin, E; Hoschl, R; Nelson, GI; Stokes, GS; Wilkes, NP, 1989)	0.28
"The purposes of this investigation were to demonstrate how computer simulations may be employed to extrapolate data obtained from a single intravenous digoxin dose to multiple oral dosing patterns and how these simulations may apply to clinical situations."	( Extension of the serum digoxin concentration--response relationship to patient management. Bourne, DW; Kolibash, AJ; Kramer, WG; Lewis, RP; Reuning, RH, 1989)	0.79
" A dosage selection based on PDC assessment led to a decrease of digitalis toxicity under 4%."	( Clinical utility of plasma digoxin measurements. Cristodorescu, R; Deutsch, G; Drăgan, S, )	0.43
"The relative steady-state bioavailability of two oral digoxin dosage forms was studied in 17 subjects with malabsorption syndromes."	( Absorption of digoxin from tablets and capsules in subjects with malabsorption syndromes. Bustrack, JA; Fitch, DD; Hammond, JE; Heizer, WD; Hull, JH; Pittman, AW, 1989)	0.89
" Complete norepinephrine dose-response curves in 8 rats with chronic and 28 with early 1K1C hypertension, compared with appropriate normotensive control rats, showed unchanged thresholds and ED50 values."	( The vascular Na+-K+ pump in experimental hypertension. Overbeck, HW, 1987)	0.27
" The dose-response curve of this compound was parallel to that of ouabain."	( The effects of urinary digitalislike factor on cultured vascular smooth muscle cells. Goto, A; Ishiguro, T; Ishii, M; Sugimoto, T; Yamada, K; Yoshioka, M, 1988)	0.27
" Drugs whose dosage may need to be altered in pregnancy include most anticonvulsants, lithium, digoxin, certain beta-blockers, ampicillin and cefuroxime; for drugs which have not been specifically investigated, no generalizations are possible."	( The fate of drugs in pregnancy. Mucklow, JC, 1986)	0.49
" Also, no difference in efficacy of either drug was observed and changes in dosing of digoxin were not required."	( Drug interaction studies and encainide use in renal and hepatic impairment. Gallo, DG; Quart, BD; Sami, MH; Wood, AJ, 1986)	0.49
" The influence of cardiac glycoside dosage shown by the present work indicates that the digoxin-quinidine interaction and possibly analogous interactions involving other cardiac glycosides, may not always be readily detectable from plasma concentration data."	( The effect of digoxin dosage on the digoxin-quinidine interaction in the bile duct-cannulated rat. Hewick, DS; Ostenfeld, T, 1987)	0.86
" The studies after single and multiple dosing were conducted in CHF patients."	( Clinical pharmacokinetics of ibopamine on different diseases and conditions. Lodola, E; Ventresca, GP, 1988)	0.27
" The effects of ramipril, a new angiotensin converting enzyme inhibitor, on serum digoxin concentration after multiple dosing were studied in 12 healthy volunteers."	( Pharmacokinetic interaction study with ramipril and digoxin in healthy volunteers. Doering, W; Irmisch, R; König, E; Maass, L, 1987)	0.75
"A randomized, crossover, single-blind study compared the efficacy and dosing accuracy of digoxin and digitoxin in 15 ambulatory patients wth congestive heart failure."	( A comparative trial of digoxin and digitoxin in the treatment of congestive heart failure. Bussey, HI; Gaspard, JJ; Hawkins, DW; Walsh, RA, 1988)	0.81
" The format of the trial (chronic versus single digoxin dosing in cardiac patients; chronic versus single digoxin dosing in normal subjects) and the method of assessment of alterations in digoxin handling (formal determination of digoxin clearance, comparison of multiple or single digoxin measurements during various phases of trial) also impact greatly on the clinical relevance of such investigations."	( Pharmacokinetic drug interactions between digoxin and antiarrhythmic agents and calcium channel blocking agents: an appraisal of study methodology. Antman, EM; Arnold, JM; Friedman, PL; Smith, TW, 1987)	0.79
" Vagotomy and atropine prevented the effect of morphine so that the dose-response relationships and the mean digoxin dose at onset of ventricular arrhythmias and the development of fatal arrhythmias were not significantly different from the control group receiving saline."	( The interrelationship of morphine and the parasympathetic nervous system in digoxin-induced arrhythmias in the guinea-pig. Rabkin, SW, 1988)	0.72
" Among these are various disease states, obesity, fluid imbalances, the drug dosage form used, and concurrent drug use."	( Use of serum drug concentrations in surgical patients. Connors, JE; DiPiro, JT; Sisley, JF, 1988)	0.27
" After digoxin dose titration to produce therapeutic levels, digoxin dosage remained constant throughout the balance of the study."	( Comparative effects of nadolol-digoxin combination therapy and digoxin monotherapy for chronic atrial fibrillation. Brewington, J; Gore, R; Olukotun, AY; Zoble, RG, 1987)	1.01
" Reduced dosage was easily detected in the marker results."	( Minimal doses of digoxin: a new marker for compliance to medication. Heinonen, OP; Javela, K; Mäenpää, H; Mälkönen, M; Manninen, V; Pikkarainen, J, 1987)	0.61
" In the poor compliance group, defined with the use of the digoxin marker, there was 39% of subjects who returned less than 5% of their capsule dosage or reported a deviation less than 5%."	( Comparison of the digoxin marker with capsule counting and compliance questionnaire methods for measuring compliance to medication in a clinical trial. Heinonen, OP; Mäenpää, H; Manninen, V, 1987)	0.85
"2% did not result in dosage adjustments when indicated."	( Effect of data collection method on results of serum digoxin concentration audit. Davis, SK; Gadsden, RH; Leman, RB; Makela, EH; Miller, WA; Piveral, K; Pleasants, RA, 1988)	0.52
" The maximum plasma concentration, time of maximum concentration, area under the curve during a dosing interval and steady-state trough plasma concentration for digoxin, during and after concomitant doses of cibenzoline were similar to those before administration, indicating that cibenzoline did not affect the pharmacokinetics of digoxin."	( Effect of oral cibenzoline on steady-state digoxin concentrations in healthy volunteers. Givens, SV; Khoo, KC; Massarella, JW; Parsonnet, M, 1988)	0.73
" Consequently, digoxin dosing based on monitoring drug concentration may be futile."	( Endogenous digoxin-like substance(s) associated with uneventful and high-risk pregnancies. Farine, D; Grundmann, H; Heyes, J; Koren, G; MacLeod, SM; Soldin, S; Taylor, J, 1988)	1.02
" Pharmacokinetics should underlie the rational use of drugs and when a therapeutic range is known, the achievement of safe and effective target concentrations may be assured by a dosage regimen computed for a given administration schedule."	( Dynamical dosage regimen calculations in linear pharmacokinetics. Bruno, R; Cano, JP; Iliadis, A, 1988)	0.27
"A 2 months old girl was given a tenfold increased dosage of Beta-Methyldigoxin for 2 weeks and subsequently developed severe symptoms of glycoside intoxication."	( [Course of chronic life-threatening digitalis poisoning in infancy with immunopharmacologic treatment using antidigoxin Fab of sheep]. Arnold, D; Berger, S; Hannack, D; Lasch, P; Niessen, KH; Teufel, M, 1988)	0.72
" On the 3rd day of the pengitoxin dosage schedule, a mean plasma level of 18."	( Pharmacokinetics of pengitoxin and its therapeutic efficacy in congestive heart failure. Haustein, KO; Wesser, M, 1988)	0.27
" On day 10, 16 serial blood samples were collected over a 24-h dosing interval and analyzed by radioimmunoassay (RIA) (Concept 4, Micromedic Systems), fluorescence polarization immunoassay (FPIA) (TDx, Abbott Laboratories), and affinity column-mediated immunoassay (ACMIA), (aca, duPont Instruments)."	( Lack of apparent effect of assay methodology on the pharmacokinetics of digoxin. Blum, RA; Crass, RE; DeVito, JM; Gadsden, RH; Leman, RB; Pleasants, RA, 1987)	0.51
"We have designed a simple nomogram for predicting digoxin dosage and have tested it prospectively in two consecutive studies."	( A simple aid to digoxin prescribing. Johnston, GD; McDevitt, DG; Taggart, AJ, 1987)	0.87
" Plasma levels of digoxin and felodipine were measured before dosage and 30, 60 and 90 minutes and 2, 3, 4, 6, 8, 10 and 24 hours after the first dose and after 1 week of therapy (steady state)."	( Pharmacokinetics of felodipine and effect on digoxin plasma levels in patients with heart failure. Billing, E; Lundman, T; Moberg, L; Olsson, G; Rehnqvist, N, 1987)	0.87
" We have compared the effect on heart rate variability, of doubling the digoxin dosage or adding verapamil 120 mg daily in a randomized cross-over study in 14 patients."	( Towards improved control of atrial fibrillation. Channer, KS; James, MA; Papouchado, M; Pitcher, DW; Rees, JR, 1987)	0.51
" This might be related to a slightly faster release of digoxin from the product A dosage form, as was seen from the dissolution test data."	( Single dose bioavailability of two different digoxin tablets. Grasmeijer, G; Gusdorf, CF; Jedema, JN; Jonkman, JH; van der Boon, WJ, 1987)	0.78
"Some physicians regard patients of Geriatric Units as a homogeneous population with respect to digoxin dosage requirements."	( Prescribing digoxin in geriatric units: the unexplained variability in dosage requirements. Denham, MJ; Deshmukh, AA; Dobbs, RJ; Dobbs, SM; Nicholson, PW; O'Neill, CJ; Royston, JP, 1987)	0.87
" Also, for each patient, the difference between dosage regimens that had been established by means of SDMs and those regimens that would have been estimated by the method of Dobbs et al."	( An evaluation of a clinical pharmacokinetic service for serum digoxin levels. Blain, L; Michalko, KJ, 1987)	0.51
"The proarrhythmic potential of digoxin, administered in a therapeutic dosage regimen, was evaluated in conscious dogs in the subacute phase of myocardial infarction."	( Facilitation of lethal ventricular arrhythmias by therapeutic digoxin in conscious post infarction dogs. Lucchesi, BR; Lynch, JJ; Montgomery, DG, 1986)	0.8
" Patient population estimates were then derived to predict the quinidine dosage necessary to achieve given plasma concentrations."	( Quinidine dosage in children using population estimates. Burckart, GJ; Marin-Garcia, J, 1986)	0.27
" According to this equation we suggest a dosing schedule for digoxin in VLBW infants with impaired renal function."	( Estimation of digoxin dosage in VLBW infants using serum creatinine concentrations. Gortner, L; Hellenbrecht, D, 1986)	0.87
"The effect of incremental diltiazem dosing during concomitant digoxin administration over a four-week period in eight healthy adult volunteers (mean age, 28 +/- 4 years) was studied."	( No increase in serum digoxin concentration with high-dose diltiazem. Boden, WE; Bough, EW; Korr, KS; More, G; Sharma, S; Shulman, RS; Young, PM, 1986)	0.83
"This paper describes a general approach to compute steady-state dosage regimens."	( Steady-state dosage regimen calculations in linear pharmacokinetics. Bruno, R; Cano, JP; Iliadis, A, 1986)	0.27
" The dosage of the antibody should be sufficiently high to bind digoxin in the most severe cases of poisoning."	( Kinetics of the Fab fragments of digoxin antibodies and of bound digoxin in patients with severe digoxin intoxication. Kaufmann, B; Neubert, P; Schaumann, W; Smolarz, A, 1986)	0.79
"A cardiac patient had to be given a very high dosage of digoxin to attain therapeutic plasma level."	( The significance of the enterohepatic circulation on the metabolism of digoxin in patients with the ability of intestinal conversion of the drug. Klitgaard, NA; Nørregaard-Hansen, K; Pedersen, KE, 1986)	0.75
" Thus protein binding could not account for the differences in dosage and susceptibility of digoxin in newborns and infants as compared to adults."	( Comparison of the serum protein binding of digoxin in premature and mature newborns, infants and adults. Genz, T; Hubert, U; Reinhardt, D, 1985)	0.75
"For many drugs estimation of a safe and effective dosage regimen is difficult."	( Computerized drug therapy: application of the hand-held microcomputer to dosage regimen design. Brouwer, KR; Cook, J; Gwilt, PR; Steinke, M, 1985)	0.27
" A thorough understanding of the applied pharmacology, dosage recommendations, toxicity, and practical considerations must be attained before these drugs can be used effectively."	( Pharmacology and pharmacokinetics of drugs used to treat cardiac disease in horses. McGuirk, SM; Muir, WW, 1985)	0.27
"The literature reviewed herein clearly demonstrates the poor correlation between drug dosing and the ability to achieve a specific serum drug concentration and between drug dosing and clinical response, especially for drugs with a narrow therapeutic index."	( Comparison of drug dosing methods. Brater, DC; Burton, ME; Vasko, MR, )	0.13
" Concurrent administration of triacetyloleandomycin with drugs whose metabolism is known to be affected or that could potentially be affected should be avoided unless appropriate adjustments in dosage are made."	( Pharmacokinetic interactions of the macrolide antibiotics. Ludden, TM, )	0.13
" The dosage of digoxin-specific Fab was calculated to be equimolar to the amount of cardiac glycoside in the patient's body."	( Treatment of 63 severely digitalis-toxic patients with digoxin-specific antibody fragments. Butler, VP; Haber, E; Smith, TW; Wenger, TL, 1985)	0.87
" Coexisting disease states, such as renal or hepatic dysfunction, may require individualized dosing of these agents."	( Individualization of calcium entry-blocker dosage for systemic hypertension. Piepho, RW, 1985)	0.27
" These findings show that changes in the oral dosage formulation of digoxin from a tablet to a solution-in-capsule form can overcome the adverse effects of high-dose cancer chemotherapy on drug absorption, and suggest a similar approach may be successful for other drugs."	( Effects of high-dose cancer chemotherapy on the absorption of digoxin in two different formulations. Bjornsson, TD; Christenson, R; Huang, AT; Jacob, DS; Roth, P, 1986)	0.75
" We tested inter- and intrapatient variability during 4-week periods of dosing with digoxin capsules and tablets in 28 subjects with cardiac disease."	( Variability of steady-state digoxin kinetics during administration of tablets or capsules. Budnitz, E; Johnson, BF; Lindenbaum, J; Marwaha, R, 1986)	0.79
"To determine whether nifedipine or diltiazem affect digoxin kinetics, glycoside plasma concentrations and renal excretion were measured before and during dosing in 23 patients with cardiac insufficiency achieving steady-state conditions."	( Effects of nifedipine and diltiazem on plasma levels and renal excretion of beta-acetyldigoxin. Kuhlmann, J, 1985)	0.74
" Only 47% of the patients were on a dosage considered to be effective by serum digoxin analysis, whereas 38% of the patients had levels below the therapeutic range; 51% of the patients had been treated with pediatric or semipediatric doses only."	( Digoxin treatment and control in the elderly. Abraham, AS; Sonnenblick, M, 1985)	1.94
" Dosage differences explained 7% to 60% of the variability in digoxin plasma concentrations in various age and weight groups."	( Maintenance digoxin dosage and steady-state plasma concentration in infants and children. Chow-Tung, E; Hastreiter, AR; van der Horst, RL; Voda, C, 1985)	0.89
"Nine patients (median age 78 years, range 62-92) treated with a constant oral dosage of digoxin were evaluated for the effect of trimethoprim on serum digoxin values."	( Digoxin-trimethoprim interaction. Bartram, R; Kastrup, J; Mølholm Hansen, J; Petersen, P, 1985)	1.93
" This study evaluated whether digoxin solution in capsules, a new dosage form with 90% to 100% bioavailability, would reduce such alterations, specifically those caused by cholestyramine and propantheline bromide."	( A steady-state evaluation of the effects of propantheline bromide and cholestyramine on the bioavailability of digoxin when administered as tablets or capsules. Brown, DD; Hull, JH; Long, RA; Schmid, J, )	0.63
" The development of digoxin toxicity in the context of accepted therapeutic dosing to treat heart failure due to a cerebral arteriovenous malformation is discussed."	( Digoxin toxicity in a premature infant: treatment with Fab fragments of digoxin-specific antibodies. Butler, VP; Doyle, EF; Friedman, D; Haber, E; Presti, S; Saslow, J; Smith, TW, 1985)	2.04
" Thus, the influence of multiple plasma exchanges on the steady-state kinetics of digoxin and digitoxin will be limited and dosage adjustment is not required, if these drugs are given after - not before - the procedure and hypoalbuminaemia is corrected."	( Effect of plasma exchange on the steady-state kinetics of digoxin and digitoxin. Distler, A; Keller, F; Kreutz, G; Offermann, G; Vöhringer, HF, )	0.6
" It is suggested that insulin, glucose, and potassium given by the intravenous route in adequate dosage forms a useful adjunct to the management of severe congestive heart failure."	( Insulin, glucose, and potassium in the treatment of congestive heart failure. Allison, SP; Burns-Cox, CJ; Morley, CJ, 1972)	0.25
"A dosage schedule for digoxin medication is presented which has proved effective and safe in children of different ages with heart failure due to a variety of cardiac conditions."	( Plasma digoxin concentration in children with heart failure. Coltart, DJ; Cree, JE; Howard, MR, 1973)	1.02
"The rapid appearance of digoxin in the blood suggests that the oral route of administration is adequate for most patients who require rapid digitalization, and the timing of maintenance dosage in relation to meals is unimportant."	( Plasma concentrations of digoxin after oral administration in the fasting and postprandial ste. Chamberlain, DA; Howard, M; Smith, TW; White, RJ, 1971)	0.86
" To prevent adverse reactions in geriatric patients, prescriptions should be limited to a few essential drugs, dosage reduced, and dosing regimens simplified."	( [Side effects of drugs in the geriatric patient (author's transl)]. Follath, F, 1981)	0.26
" The pharmacodynamic response was a dose-related fall in the systemic arterial pressure, both supine and standing; dose-response effects were most evident in the upright posture."	( The pharmacokinetic, pharmacodynamic and haemodynamic effects of acute and chronic alpha-adrenoceptor blockade in chronic heart failure. Silke, B; Taylor, SH, 1981)	0.26
"375 mg digoxin dosing periods, respectively."	( Effects of oral digoxin on ventricular ectopy and its relation to left ventricular function. Berger, HJ; Cunningham, M; Gradman, AH; Harbison, MA; Zaret, BL, 1983)	1.07
"The pharmacokinetic properties and dosage guidelines for digoxin in pediatric patients with congestive heart failure are reviewed."	( Digoxin pharmacokinetics and dosage requirements in pediatric patients. Bendayan, R; McKenzie, MW, )	1.82
" Because of the complex pharmacokinetics associated with multiple-dose administration and the variation in individual patient responsiveness to the drug, 'standard' dosing recommendations are difficult to determine; use of verapamil must be titrated to a clinical end-point."	( Clinical pharmacokinetics of verapamil. Blouin, RA; Hamann, SR; McAllister, RG, )	0.13
" The aim of this study was to establish a rapid system of drug assay, to report the result, to assess the influence of pathological and clinical factors on the pharmacokinetics of certain drugs, and to use a computer to determine the optimum dosage of drugs."	( Clinical pharmacokinetics: a comprehensive system for therapeutic drug monitoring and prescribing. Bryson, SM; Derkx, FH; Fotheringham, GH; Joel, SE; Kelman, AW; Thomson, AH; Whiting, B, 1984)	0.27
" Although the monovalent Fab'--beta-galactosidase conjugate yields a more sensitive assay and dose-response curves that are linear over a wider range, the divalent F(ab')2--beta-galactosidase conjugate provides an assay with adequate sensitivity and extremely good precision, and is generally easier to synthesize reproducibly."	( Affinity-column-mediated immunoenzymometric assays: influence of affinity-column ligand and valency of antibody-enzyme conjugates. Freytag, JW; Lau, HP; Wadsley, JJ, 1984)	0.27
" The highest digoxin concentrations at 1 hr post dosing were found in lymph nodes, adrenals, gallbladder (including contents), liver and kidney respectively."	( The effect of immunization with digoxin-specific antibodies on digoxin disposition in the mouse. Griffiths, NM; Hewick, DS; Stevenson, IH, 1984)	0.92
" The Bayesian approach in pharmacokinetics involves the prediction of pharmacokinetic values, dosage regimens, and serum concentrations for drugs."	( Bayesian approaches in pharmacokinetic decision making. Barr, JT; Schumacher, GE, )	0.13
"The effects of orally administered propafenone on ejection fraction (EF) determined by radionuclide angiography were studied in 2 groups of patients receiving different dosing regimens."	( Effect of propafenone on left ventricular ejection fraction. Baker, BJ; de Soyza, ND; Dinh, H; Franciosa, JA; Kroskey, D; Murphy, ML, 1984)	0.27
" The dosage range that is likely to cause the hypotensive effect without the potassium loss has been called the "therapeutic window."	( Effect of bioavailability on dose-response relationships. Goldman, P, 1984)	0.27
" Metoclopramide reduced the time to reach peak concentration for both digoxin dosage forms."	( Effect of metoclopramide on digoxin absorption from tablets and capsules. Bustrack, JA; Hull, JH; Johnson, BF; Marwaha, R; Urbach, DR, 1984)	0.8
" Digoxin present in serum and urine samples collected for 48 h after dosing was quantified by RIA."	( Bioavailability of digoxin capsules and tablets: effect of coadministered fluid volume. Bustrack, JA; Christenson, RH; Foster, JR; Hammond, JE; Hull, JH; Katz, JD, 1984)	1.51
" On the other hand digitalis administered according to age, sex, weight, kidney function, together with amiodarone, can be given at full dosage in patients without cardiac failure."	( [Pharmacological and clinical research on the interaction of digitalis and amiodarone in heart disease patients with varying degrees of cardiac insufficiency]. Aquili, C; Ferrari, M; Fornaro, G; Fortina, A; Padrini, R; Piovan, D; Rossi, P; Tomassini, G, 1984)	0.27
" Alteration of digoxin and digitoxin dosage during repeated plasma exchanges is not recommended, but drugs should be given after, not before plasma exchange."	( Effect of repeated plasma exchange on steady state kinetics of digoxin and digitoxin. Hauff, A; Keller, F; Kreutz, G; Molzahn, M; Offermann, G; Reeck, S; Schultze, G; Vöhringer, F, 1984)	0.86
" These considerations cast serious doubts on the validity of currently accepted digoxin kinetics and dosing in preterm infants."	( Significance of the endogenous digoxin-like substance in infants and mothers. Farine, D; Heyes, J; Koren, G; MacLeod, S; Maresky, D; Soldin, S; Taylor, J, 1984)	0.78
" Thus, in patients on maintenance dose of digoxin therapy, use of large dosage of diuretics may result in hypokalemia, causing digitalis toxicity even at low serum digoxin levels."	( Digoxin toxicity and electrolytes: a correlative study. Burma, DP; Sundar, S; Vaish, SK, 1983)	1.97
" We conclude that amiodarone is highly effective in high-risk patients with complex refractory cardiac arrhythmias, and that close monitoring and prompt recognition of side effects and appropriate adjustment of dosage or institution of supplemental or replacement therapy (in less than 5% of patients) will allow continuation of amiodarone."	( Evaluation of amiodarone therapy in the treatment of drug-resistant cardiac arrhythmias: long-term follow-up. Hamer, A; Mandel, WJ; Peter, T; Weiss, D, 1983)	0.27
"To demonstrate the usefulness of a recently published nomogram method for clinical pharmacokinetics two examples for dosage regimen adjustment (gentamicin and digoxin) are given."	( A simple method for dosage regimen adjustment. Ritschel, WA, )	0.33
"The generation by intestinal bacteria of large amounts of cardioinactive metabolites of digoxin with a reduced lactone ring (digoxin reduction products, or DRP) may be associated with increased dosage requirements."	( Decreased digoxin cardioinactive-reduced metabolites after administration as an encapsulated liquid concentrate. Butler, VP; Dobkin, JF; Lindenbaum, J; Rund, DG; Saha, JR, 1983)	0.89
"Eleven LBW infants were studied to assess the predictability of individual digoxin dosage requirement from a single serum digoxin concentration (SDC) at various times within the first dosing interval."	( The 24-hour serum digoxin level as a prognosticator of dosage requirement in low-birth-weight (LBW) infants. Collins-Nakai, RL; Ng, PK, 1983)	0.83
"The clarification of a suspicion of poisoning at all times poses a problem to the forensic toxicologist, when a narrow margin of therapeutic safety and a low dosage coincide as in cases of digoxin poisoning."	( [Classification of digoxin concentrations in blood and tissues in cases under suspicion of poisoning]. Aderjan, R; Härdle, W, 1983)	0.78
" The initial dosage of A was 1200 mg daily for 5 days to achieve saturation, followed by a maintenance dose of 200-400 mg daily."	( [Interaction of amiodarone and digoxin]. Nager, F; Nager, G, 1983)	0.55
" In the dose-response curve half maximal positive inotropism occurred at approx."	( Effects of acrihellin on cardiac contractility in comparison to various inotropic interventions. Achenbach, C; Wiemer, J; Ziskoven, R, 1983)	0.27
"This paper describes a program which can predict multiple-dose blood level curves of any drug administered orally or intravenously with up to a maximum of three changes in the dosage regimen at any time during the treatment period."	( Prediction of multiple-dose blood level curves of drugs with rapid changes in doses and/or dosing intervals. Collins-Nakai, RL; Ng, PK, 1983)	0.27
" Since more than half had signs of early renal function impairment, creatinine clearance should be taken into account when determining the dosage of a digoxin preparation especially in elderly patients; alternatively, digitoxin should be prescribed."	( [Epidemiology of digitalis medication. Results of the Munich blood-pressure study]. Döring, A; Keil, U; Koenig, W; Mraz, W; Pöppl, SJ; Stieber, J, 1984)	0.47
" Some calcium antagonists have been shown to alter digoxin kinetics and changes in digoxin dosage have been recommended."	( The effect of nifedipine on serum digoxin concentrations in patients. Akers, S; Raizner, A; Schwartz, JB, 1984)	0.8
" According to our findings there is more danger of digitalis toxicity in patients with cirrhosis of the liver on a standard dosage of metildigoxin than on a standard dosage of beta-acetyldigoxin."	( Changes in metildigoxin pharmacokinetics in cirrhosis of the liver: a comparison with beta-acetyldigoxin. Bonelli, J; Rameis, H; Waginger, H; Woodcock, B, 1984)	0.82
" To obtain better dosage the pharmacokinetics of digoxin are discussed, as well as changes in it in the process of ageing."	( [Pharmacokinetics of digoxin in the aged]. van der Aa, GC, 1984)	0.84
" Dosage and parameters of toxicity should be carefully monitored in patients receiving digoxin who develop acute renal failure."	( Rising serum digoxin without further dosage in acute renal failure. Fine, A; Gallway, B; Gault, MH; Vasdev, S, 1984)	0.86
" Our data suggest that when indomethacin is added to digoxin therapy, the digoxin dosage should be reduced by 50% until urine output and digoxin serum levels can be better assessed."	( Effects of indomethacin on digoxin pharmacokinetics in preterm infants. Koren, G; MacLeod, SM; Perlman, M; Zarfin, Y, 1984)	0.81
" The results indicate that the cells adapt to chronic exposure to 'therapeutic' dosage of digoxin with an overcompensatory synthesis of new receptors, a possible mechanism through which the normal intraerythrocytic ionic equilibrium is re-established."	( Digitalis 'receptors' during chronic digoxin treatment. Ambrosioni, E; Malini, PL; Marata, AM; Strocchi, E, )	0.63
" dosing or 3 and 8 h after repeated oral dosing in the coadministered group were significantly decreased as compared with those in the group received warfarin alone."	( Effect of digoxin on plasma clearance and anticoagulant effect of warfarin in rats. Iwaki, M; Konishi, Y; Ogiso, T, 1984)	0.67
" New dosage guidelines have resulted from these studies."	( [Which digitalis therapy is still justified today? (author's transl)]. Kümmell, HC, 1980)	0.26
" In most studies reporting malabsorption, a solid dosage form of digoxin was used."	( Perspectives on digoxin absorption from small bowel resections. Kumer, KP; Nwangwu, JT; Nwangwu, PU, 1983)	0.85
" Atropine given in higher dosage (80mg/kg) with digoxin (40mg/kg) produced arrhythmias in 100% of rats as did digoxin alone, but significantly shortened their onset and modified the types of arrhythmias seen."	( Modification of digoxin induced arrhythmogenicity in adult rats following atropine administration. Kaplanski, J; Martin, O; Weinhouse, E, 1983)	0.87
" Our results indicate the need for very exact monitoring of digoxin dosage during cytostatic therapy."	( Inhibition of digoxin absorption but not of digitoxin during cytostatic drug therapy. Kuhlmann, J, 1982)	0.87
" Serum level determinations can also be useful for establishing the best individual dosage of benzodiazepines, phenothiazines, and tricyclic antidepressants."	( Serum drug concentrations in clinical perspective. Koch-Weser, J, 1981)	0.26
" On the basis of this assumption maintenance dosage regiments must be adjusted."	( Digitalis therapy in renal failure with special regard to digitoxin. Rietbrock, N; Vöhringer, HF, 1981)	0.26
" Prediction error analysis, however, allowed us to determine the best set of pharmacokinetic equations for a first approximation to appropriate digoxin maintenance dosage requirements, namely Gault-estimated elimination rate constant, measured Clcr, and Jusko-estimated volume of distribution."	( Re-examination of digoxin dosage regimen: comparison of the proposed nomograms or formulae in elderly patients. Hirayama, H; Ishizaki, T; Sasaki, T; Suganuma, T; Tsujimoto, G, 1982)	0.8
"To establish whether there is a difference between infants and adults in the relationship of serum levels of digoxin to dosage or the ratio of myocardial to serum digoxin levels, the concentrations of digoxin in right atrial appendage (RAA) and serum were measured in 12 infants and 17 adults undergoing open heart surgery."	( Myocardial vs serum digoxin concentrations in infants and adults. Arom, KV; Ludden, T; Oswalt, JD; Park, MK; Rogers, J, 1982)	0.8
" The furosemide dosage was decreased and eventually discontinued as clinical improvement occurred."	( Medical management of congestive heart failure in a horse. Brumbaugh, GW; Hodge, TG; Thomas, WP, 1982)	0.26
" We conclude that no alteration is required in digoxin dosing when aspirin is used."	( Kinetics of the digoxin-aspirin combination. Comess, KA; Fenster, PE; Finley, PR; Hanson, CD, 1982)	0.87
" Two methods of estimating creatinine clearance and two estimates of ideal body weight were employed as input variables using the 12 dosing methods."	( Evaluation of various methods of digoxin dosing. Conrad, K; Hager, WD; Jones, WN; Perrier, D; Trinca, CE, )	0.41
" about half the effective dosage initially considered."	( [Digitoxin poisoning: reversing ventricular fibrillation with Fab fragments of anti-digoxin antibody]. Abuaf, N; Baud, F; Bismuth, C; Bolo, A; Domart, Y; Fournier, PE; Gailliot, M; Pontal, PG; Schermann, JM, 1982)	0.49
" In 45 cases the digoxin dose had to be altered, partly even several times, whilst only in 23 patients an alteration of the dosage of the nitrate compositions had to be done, independently from the digoxin dose."	( [Do fixed combinations of digoxin and nitrates have a therapeutic advantage?]. Mattern, HJ, 1981)	0.9
"Healthy dogs were treated once a day for 26 days with a liquid, oral dosage form of digoxin (0."	( Serum digoxin concentrations in dogs before, during, and after concomitant treatment with phenobarbital. Ganjam, VK; Nachreiner, RF; Pedersoli, WM, 1980)	0.97
" However, over a 24-hour dosing interval, digoxin concentrations in each patient studied during heart failure were either similar or higher than those observed when the patient became compensated."	( Digoxin pharmacokinetics in congestive heart failure. Adir, J; Applefeld, MM; Crouthamel, WG; Roffman, DS, )	1.84
" Overall, 67 percent of the serum digoxin assays were judged to be appropriate, particularly those requested for evaluation of possible digitalis toxicity or the dosage in renal impairment, but only 43 percent of the assays used to assess maintenance therapy or the patient's compliance were deemed appropriate."	( Evaluation of the clinical use of serum digoxin radioimmunoassays. McLeod, DC; Volpone, MT, 1981)	0.81
"Digoxin monitoring was examined according to 13 criteria in two nursing homes: 1) an intermediate care facility (ICF) with private physicians, and 2) a skilled care (SCF) plus ICF with 3 housestaff physicians from a identify all patients receiving digoxin, 2) evaluate dosage patterns, 3) evaluate monitoring patterns, and 4) detect possible toxic reactions and determine whether management was appropriate."	( Monitoring digoxin therapy in two long-term facilities. Carter, BL; Garnett, WR; Small, RE, 1981)	2.1
" The criteria specified the indication for each drug, performance data, and dosage adjustments with SDA results."	( Effect of pharmacist intervention on the use of serum drug assays. Birmingham, PH; Cohen, SS; Levin, B, 1981)	0.26
"The reproducibility of drug absorption within a given subject as well as the evaluation of bioavailability of two digoxin dosage forms were studied."	( The assessment of the intrasubject variability in digoxin absorption in man from two oral dosage forms. Ayers, JW; Chao, GC; Hallmark, M; Sakmar, E; Schwartz, RA; Stoll, RG; Wagner, JG; Weidler, DJ; Yacobi, A, 1981)	0.73
" Digoxin loading and maintenance dosage should be calculated on the basis of IBW, which reflects lean body mass, rather than TBW, which reflects adipose tissue weight in addition to lean body mass."	( Digoxin disposition in obesity: clinical pharmacokinetic investigation. Abernethy, DR; Greenblatt, DJ; Smith, TW, 1981)	2.62
" Long-term vasodilator therapy may alter the maintenance dosage of digoxin required for optimal treatment of patients in congestive heart failure."	( Acute vasodilator therapy increases renal clearance of digoxin in patients with congestive heart failure. Benowitz, NL; Carlson, CJ; Cogan, JJ; Humphreys, MH; Rapaport, E, 1981)	0.75
"6 ng/ml) at approximately 1 hour after dosing and had a half-life of 28."	( Pharmacokinetics of a single, orally administered dose of digoxin in horses. Belmonte, AA; McCullers, RM; Pedersoli, WM; Ravis, WR, 1981)	0.51
" There is greater danger of digitalis toxicity in patients with cirrhosis of the liver on standard dosage of beta-methyldigoxin than on standard dosage of beta-acetyldigoxin."	( [Pharmacokinetics of beta-methyldigoxin and beta-acetyldigoxin in patients with cirrhosis of the liver (author's transl)]. Bonelli, J; Hruby, K; Rameis, H; Waginger, H, 1981)	0.75
" Data from a drug surveillance study showed that 10 of 32 patients had a significant change in plasma digoxin concentration after admission to hospital, indicating deviations in compliance with the dosage regimen prior to hospitalisation."	( Digoxin and Phenytoin analyses as part of consultations in clinical pharmacology: a study on the use of drugs. Bergman, U; Rane, A; Sjöqvist, F; Wiholm, BE, 1981)	1.92
" Ninety-two samples, representing three manufacturers and an adequate cross-section of the country, as well as typical dosage forms and packaging variations, were selected for laboratory analyses of content uniformity, strength, dissolution, identification, and related fluorescing substances."	( Stability of digoxin tablets collected from U.S. hospitals. Belson, JJ; Juhl, YH; Moyer, ES; Page, DP; Shroff, AP, 1981)	0.63
" The dosage aimed at a mid-rate attainment of the plateau concentration in the blood."	( [Pharmacokinetic analysis of the fluctuation in digitalis bloodlevels during oral therapy with beta-methyldigoxin in children with heart insufficiency (author's transl)]. Bleyl, H; Netz, H; Rautenburg, HW; von Hattingberg, HM, 1980)	0.47
" the dosage of 0,5 mg digoxin (group 1) induced accumulation to toxic levels (2,14 mg/ml)."	( [Digoxin therapy in patients with long-term digitalis therapy. Comparison of the digoxin blood level after oral administration of digoxin and beta-methyldigoxin]. Hennersdorf, G; Leithäuser, H, 1980)	1.49
"Recent developments of clinical pharmacology show that in particular circumstances the determination of the plasmatic levels of drugs seems to be the best way to insure the best dosage schedules for each patient."	( Clinical pharmacokinetics: the pharmacological monitoring of plasmatic levels in therapy. Bonora, MR; Guaglio, R; Rondanelli, R; Terzoni, PA, 1980)	0.26
" There was a preference for initiating treatment with a diuretic rather than digoxin and for commencing digoxin in daily maintenance dosage rather than with a loading dose."	( Survey of cardiac failure therapy in Australian medical practice: dependence on digoxin level for diagnosis of toxicity. Read, TR; Schapel, GJ, 1980)	0.72
" Areas under the plasma concentration-time curves during a 24 h dosage interval were similar for the three preparations, and so was the 24 h urinary excretion of digoxin, which averaged 60-63% of the daily dose."	( Absorption of digoxin from a new microencapsulated formulation. Bergdahl, B; Bogentoft, C; Jonsson, UE; Magnusson, JO, 1980)	0.82
" Following the results, a reduction in digoxin dosage to half of the dose is recommended."	( [Interaction of digoxin and quinidine]. Haustein, KO; Oltmanns, G, 1980)	0.88
"Previous dosing schedules for digoxin in renal failure have considered the decrease in the elimination rate constant but not the decrease in the volume of distribution."	( Digoxin dosage in renal insufficiency: impracticality of basing it on the creatinine clearance, body weight and volume of distribution. Ingerowski, R; Keller, F; Molzahn, M, 1980)	1.99
" Individualized digoxin dosage regimens for the three dogs were calculated from data collected in the present experiment and data from the literature."	( Application of individualized digoxin dosage regimens to canine therapeutic digitalization. Allert, JA; Button, C; Gross, DR, 1980)	0.9
" The calculated dosage regimens were administered and resulting plasma digoxin concentrations were monitored in 5 horses and 1 pony."	( Digoxin pharmacokinetics, bioavailability, efficacy, and dosage regimens in the horse. Button, C; Gross, DR; Johnston, JT; Yakatan, GJ, 1980)	1.94
" The recommended technique facilitates dosage calculations in patients treated with digitoxin."	( Interindividual differences in the pharmacokinetics of digitoxin and digoxin during long-term treatment. Haustein, KO, 1981)	0.5
" Changes in the means between day 10 (digoxin monotherapy) and day 24 (combined therapy) for renal clearance, area under the plasma concentration-time curve during the dosing interval, and the minimum and maximum plasma digoxin concentrations did not differ significantly between the tenidap and placebo groups."	( Effect of tenidap sodium on digoxin pharmacokinetics in healthy young men. Coates, PE; Dewland, PM; Grimwood, VC; Rapeport, WG, 1995)	0.86
" All patients were New York Heart Association Functional Class II, III, or IV and had remained symptomatic despite optimal dosing with digoxin and diuretics."	( Lisinopril versus placebo in the treatment of heart failure: the Lisinopril Heart Failure Study Group. Beller, B; Bourge, RC; Bulle, T; Colfer, H; Fisher, MB; Fowles, RE; Giles, TD; Grover, J; Jessup, M; Whipple, JP, 1995)	0.49
" The concentrations of all four drugs in the sample collected during life were consistent with the dosage given and in the range accepted for normal therapy."	( Differences in amiodarone, digoxin, flecainide and sotalol concentrations between antemortem serum and femoral postmortem blood. McCarthy, PT; O'Sullivan, JJ; Wren, C, 1995)	0.59
" Of particular note was the number (15 or 58%) of dosage changes or therapy cessations made to digoxin therapy for patients also receiving amiodarone which occurred as a result of clinical pharmacist intervention."	( Digoxin-quinidine and digoxin-amiodarone interactions: frequency of occurrence and monitoring in Australian repatriation hospitals. Bebee, R; Freitag, D; Sunderland, B, 1995)	1.95
" A dose-response relationship between serum digoxin and RQ was observed."	( Inhibition of Na(+)-K(+)-ATPase by digoxin and its relation with energy expenditure and nutrient oxidation rate. Buclin, T; Dériaz, O; Jéquier, E; Lyon, X; Schutz, Y, 1995)	0.83
" On long term evaluation in an open design (Phase II), wherein Phase I participants continued Terminalia Arjuna in fixed dosage (500 mg 8-hourly) in addition to flexible diuretic, vasodilator and digitalis dosage for 20-28 months (mean 24 months) on outpatient basis, patients showed continued improvement in symptoms, signs, effort tolerance and NYHA Class, with improvement in quality of life."	( Salutary effect of Terminalia Arjuna in patients with severe refractory heart failure. Bharani, A; Bhargava, KD; Ganguly, A, 1995)	0.29
"Despite almost three centuries of use, the appropriate dosage of digitalis in patients with chronic heart failure and normal sinus rhythm has not been well studied."	( Effects of increasing maintenance dose of digoxin on left ventricular function and neurohormones in patients with chronic heart failure treated with diuretics and angiotensin-converting enzyme inhibitors. Alam, M; Gheorghiade, M; Goldstein, S; Hall, VB; Jacobsen, G; Rosman, H, 1995)	0.56
"A 24 h intravenous dosing regimen of amiodarone was designed to reach a peak plasma concentration at 1 h and to maintain the concentration above a certain level during the infusion period."	( Acute treatment of recent-onset atrial fibrillation and flutter with a tailored dosing regimen of intravenous amiodarone. A randomized, digoxin-controlled study. Chang, MS; Chen, CY; Chiang, HT; Hou, ZY; Lin, SL; Tu, MS; Woosley, RL, 1995)	0.49
" The most common adverse events of the 54 and 28 cited as reasons for withdrawal in the felodipine and placebo groups respectively were increased need for non-study heart failure treatment (n = 10; 8%)--that is, starting new medication or changes in the dosage of existing treatment for patients given felodipine, and nausea (n = 4; 3%) for those given placebo."	( Placebo controlled trial of felodipine in patients with mild to moderate heart failure. UK Study Group. Littler, WA; Sheridan, DJ, 1995)	0.29
" Such changes in oral dosage form failed to achieve therapeutic digoxin serum concentrations in this case."	( Malabsorption of digoxin tablets, gel caps, and elixir in a patient with an end jejunostomy. Carroll, MA; Ehrenpreis, ED; Guerriero, S; Nogueras, JJ, 1994)	0.87
" Further research into the appropriate mechanisms of action and proper dosing of these drugs may lead to a renewed interest in the use of positive inotropes for chronic heart failure."	( Reassessment of digoxin and other low-dose positive inotropes in the treatment of chronic heart failure. Gheorghiade, M; Han, D; Tauke, J, 1994)	0.63
" The dosage requirements of warfarin are reduced by chloramphenicol, ciprofloxacin and other quinolones, erythromycin and some of the other macrolides, metronidazole and other imidazoles, tetracyclines, amiodarone, cimetidine (but not ranitidine), and fibrates."	( Serious drug interactions. Aronson, J, 1993)	0.29
" A maintenance dose of digoxin was administered at 24-h intervals for 7 days in the study group (n = 15); no change was made in the 12-h dosage interval in the control group (n = 15)."	( Single daily dose of digoxin for maintenance therapy of infants and children with cardiac disease: is it reliable? Bakir, M; Bilgiç, A, )	0.76
" The following pharmacokinetic parameters were determined using noncompartmental techniques: area under the curve for 24 hours (AUC24); time to maximum concentration after digoxin (tmax); maximum concentration after digoxin dosing (Cmax); concentration at 24 hours after fluvastatin or placebo (Cmin); total amount excreted in the urine over 24 hours (U24); and urinary clearance (Clren)."	( Pharmacokinetic effects of fluvastatin in patients chronically receiving digoxin. Dimenna, G; Garnett, WR; Venitz, J; Wilkens, RC, 1994)	0.71
" Patients were evaluated with serial ambulatory ECG monitoring and exercise testing during stable digoxin dosing and then with the addition of either a placebo or dl-sotalol, 80 mg/day, or dl-sotalol, 160 mg/day."	( Comparative effects of the combination of digoxin and dl-sotalol therapy versus digoxin monotherapy for control of ventricular response in chronic atrial fibrillation. dl-Sotalol Atrial Fibrillation Study Group. Bellinger, R; Brodsky, M; Powers, L; Saini, R; Weiss, R; Zoble, R, 1994)	0.77
" It is suggested that the dosage of digoxin, if it must be used, should be individualized and the serum level monitored if possible, so as to achieve best therapeutic effects with smaller doses."	( [Observations on serum digoxin-like immunoreactive substances in patients with cor-pulmonale]. Liu, JH; Shi, YS; Yu, XZ, 1993)	0.87
"In three groups (each n = 12) of unselected hospitalized patients treated either with digoxin, theophylline, or gentamicin routinely performed TDM measurement of trough steady-state plasma levels (+ peak levels in case of gentamicin) was combined with a pharmacokinetic study at steady state (multiple blood sampling during one dosing interval)."	( Generation of pharmacokinetic data during routine therapeutic drug monitoring: Bayesian approach vs. pharmacokinetic studies. Bühl, K; Drewelow, B; el Desoky, E; Engel, G; Harings-Kaim, A; Klotz, U; Meinshausen, J, 1993)	0.51
" Drug interaction studies with fluvastatin and cholestyramine (CME) demonstrated a lower rate and extent of fluvastatin bioavailability; no impact on efficacy was demonstrated when CME was given 4 h before fluvastatin dosing in clinical trials."	( Pharmacokinetics of fluvastatin and specific drug interactions. Hwang, DS; Jokubaitis, LA; Robinson, WT; Smith, HT; Troendle, AJ, 1993)	0.29
" In each dosage group, three patients were older than and three were younger than 65 years of age."	( Age-related digoxin-alprazolam interaction. Cavdar, C; Fowler, J; Guneri, S; Guven, H; Tuncok, Y, 1993)	0.66
" The importance of individual calculation of the digoxin dosing regimen in patients with renal failure is reemphasized."	( [Digoxin intoxication due to unadjusted loading dose in renal failure]. Ezra, D; Seligmann, H, 1993)	1.45
" Serum and urine collected until 120 hours after dosing were assayed for beta-MD and digoxin by high-performance liquid chromatography and fluorescence polarization immunoassay method."	( Pharmacokinetics of beta-methyldigoxin in subjects with normal and impaired renal function. Imagawa, M; Nakano, S; Nakashima, H; Tateishi, T; Tsutsumi, K, 1993)	0.8
"A rapidly absorbed new novel oral dosage form for digoxin termed 'digoxin dry elixir' was developed by the spray-drying technique."	( Development of digoxin dry elixir as a novel dosage form using a spray-drying technique. Kim, CK; Yoon, YS, )	0.74
" The exact dosage of digoxin was ascertained in 153 (87%) patients."	( Digoxin and increased mortality among patients recovering from acute myocardial infarction: importance of digoxin dose. The SPRINT Study Group. Behar, S; Boyko, V; Goldbourt, U; Kaplinsky, E; Leor, J; Rabinowitz, B; Reicher-Reiss, H, 1995)	2.05
"The results of this study suggest that dosing adjustments of digoxin may not be necessary in patients receiving concomitant sertraline administration."	( Absence of a sertraline-mediated effect on digoxin pharmacokinetics and electrocardiographic findings. Coates, PE; Dewland, PM; Forster, PL; Rapeport, WG, 1996)	0.8
" Both an internal calibration plot for NADH and a dose-response curve for digoxin in serum were constructed."	( Capillary electrophoretic enzyme immunoassay for digoxin in human serum. Ip, MP; Liu, X; Xu, Y, 1995)	0.78
" This method thus permits the investigation of digoxin metabolism and pharmacokinetics after the administration of commercial dosage forms."	( Specific and sensitive determination of digoxin and metabolites in human serum by high performance liquid chromatography with cyclodextrin solid-phase extraction and precolumn fluorescence derivatization. Reuning, RH; Sams, RA; Tzou, MC, 1995)	0.82
" Because digoxin has a narrow therapeutic index, monitoring of plasma digoxin levels and appropriate adjustment of dosage are recommended when nefazodone and digoxin are administered concurrently."	( Assessment of pharmacokinetic and pharmacodynamic drug interactions between nefazodone and digoxin in healthy male volunteers. Barbhaiya, RH; Dockens, RC; Greene, DS, 1996)	0.93
" There was no apparent etiology, and although no tachycardia was evident, low dosage transplacental digoxin therapy was immediately initiated."	( Successful outcome of idiopathic nonimmune hydrops fetalis treated by maternal digoxin. Chavkin, Y; Ergaz, Z; Finkel, AR; Guedj, P; Kupfersztain, C; Stark, M, 1996)	0.74
" The partially purified DLIF inhibits Na+, K(+)-ATPase from a porcine cerebral cortex as well as three human red blood cell membrane preparations in a dose-response fashion."	( Purification and characterization of endogenous digoxin-like immunoreactive factors in chicken blood. Cheng, HC; Chiu, DT; Lee, HH; Liu, DH; Liu, TZ; Tsai, KJ; Wei, JS, 1996)	0.55
" Procainamide dosage reduction may not be necessary in patients with chronic stable CHF who are receiving medical therapy."	( Disposition of procainamide in patients with chronic congestive heart failure receiving medical therapy. Acciaioli, J; Borzak, S; Krepostman, A; Padhi, ID; Rudis, MI; Svensson, CK; Tisdale, JE; Ware, JA; Webb, CR; Zarowitz, BJ, 1996)	0.29
" The dosing regimens were the same whether the drugs were given alone or in combination."	( Emergency management of atrial fibrillation and flutter: intravenous diltiazem versus intravenous digoxin. Rivera, AR; Schreck, DM; Tricarico, VJ, 1997)	0.51
" Digoxin-specific Fab therapy may result in dramatic recovery from digoxin intoxication, but it must be administered early and in a an adequate dosage if reductions in mortality are to be achieved."	( Advances in the management of digoxin toxicity in the older patient. Bismuth, C; Borron, SW; Muszynski, J, 1997)	1.5
"Differences in dosage may be correlated to the range of tablet strengths available in each country in our analysis."	( Dose of digoxin prescribed in the UK compared with France and the USA. Amerasinghe, AK; Saunders, KB; Saunders, KL, 1997)	0.73
" However, little is known about the dose-response to digoxin, which has a narrow therapeutic window."	( Does digoxin provide additional hemodynamic and autonomic benefit at higher doses in patients with mild to moderate heart failure and normal sinus rhythm? Eichhorn, EJ; Grayburn, PA; Hall, SA; Irani, WN; Marcoux, LG; Page, RL; Slatton, ML, 1997)	1.06
" Additionally, dose-response inhibitory effects of glycosides on PBMNC Na+,K+ ATPase enzyme activity and interleukin-2 (IL-2) secretion by PHA-stimulated PBMNC were also noted."	( Inhibition of peripheral blood mononuclear cell proliferation by cardiac glycosides. Gentile, DA; Henry, J; Katz, AJ; Skoner, DP, 1997)	0.3
"No special dosage adjustments for digoxin appear to be necessary during concomitant therapy with terbinafine."	( Effects of terbinafine on the pharmacokinetics of digoxin in healthy volunteers. Francheteau, P; Guerret, M; Tarral, A, )	0.66
" The discrepancy between the calibrators and the controls, the tendency towards lower prescription dosage and patient noncompliance with the prescribed dose all account for these findings."	( Analytic performance of digoxin laboratory monitoring. Atanassov, N; Dimitrova, R, 1997)	0.6
" Both had stable renal function within normal limits and had been maintained on a consistent dosage of digoxin."	( Two cases of clarithromycin-induced digoxin toxicity. Ehrenpreis, E; Gallagher, KL; Guerriero, SE, )	0.62
" Little justification for the use of agents or dosing in children is available."	( Pharmacologic management of supraventricular tachycardias in children. Part 1: Wolff-Parkinson-White and atrioventricular nodal reentry. Kuhn, RJ; Luedtke, SA; McCaffrey, FM, 1997)	0.3
" Additional well-designed, controlled trials are needed to further evaluate the comparative efficacy of antiarrhythmics in the management of WPW and AVNRT in children, as well as to evaluate dosing and toxicity in various age groups."	( Pharmacologic management of supraventricular tachycardias in children. Part 1: Wolff-Parkinson-White and atrioventricular nodal reentry. Kuhn, RJ; Luedtke, SA; McCaffrey, FM, 1997)	0.3
" For truly individualised therapy, it is necessary first to select a specific target goal, such as a desired serum or peripheral compartment concentration, and then to develop the dosage regimen individualised to best hit that target in that patient."	( Model-based, goal-oriented, individualised drug therapy. Linkage of population modelling, new 'multiple model' dosage design, bayesian feedback and individualised target goals. Barbaut, X; Bayard, D; Jelliffe, RW; Jiang, F; Maire, P; Milman, M; Schumitzky, A; Van Guilder, M; Wang, X, 1998)	0.3
"No dosage adjustment is required when valaciclovir and digoxin are coadministered."	( Lack of interaction between valaciclovir, the L-valyl ester of aciclovir, and digoxin. Layton, G; Peck, RW; Posner, J; Soul-Lawton, JH; Weatherley, BC, 1998)	0.78
" The well tolerated highest daily dosage has to be used."	( [Digitalis, diuretic and vasodilator treatment of cardiac failure]. Juillière, Y, 1997)	0.3
" The 36 patients on a constant dosage took 74."	( [Ambulatory therapeutic noncompliance of the aged treated with digoxin]. Cuena Boy, R; Ortiz de Apodaca Ruiz, MA, 1998)	0.54
" Saliva may be used as a noninvasive method of measuring gentamicin serum concentrations to guide dosage adjustments in patients administered the drug once-daily."	( Clinical relevance of therapeutic drug monitoring of digoxin and gentamicin in the saliva of children. Aladjem, M; Berkovitch, M; Bistritzer, T; Burtin, P; Chen-Levi, Z; Dagan, T; Freedom, R; Koren, G, 1998)	0.55
" It differs from ouabain by three criteria: a preincubation with the membranes is required for full activity, no effect on the rat cerebral alpha3 isoform and a steep dose-response curve with the same apparent potency for rat alpha2 and alpha1 isoforms of high (10(-7) M) and low affinity (3 x 10(-5) M) for ouabain."	( Inhibition of rat Na+/K+-ATPase isoforms by endogenous digitalis extracts from neonatal human plasma. Balzan, S; Crambert, G; Decollogne, S; Ghione, S; Lelièvre, LG; Montali, U; Paci, A, )	0.13
" Following a 7-day washout period, volunteers crossed over to the other dosing regimen."	( Tiagabine, a novel antiepileptic agent: lack of pharmacokinetic interaction with digoxin. Jansen, JA; Jonkman, JH; Pedersen, PC; Snel, S; van Heiningen, PN, 1998)	0.53
" ACE inhibitor dose-response analysis used the discharge dose of ACE inhibitor, converted to enalapril-equivalent doses and adjusted for renal function."	( Impact of angiotensin-converting enzyme inhibitor underdosing on rehospitalization rates in congestive heart failure. Adelman, M; Forrest, A; Hawari, FI; Izzo, JL; Luzier, AB; Schentag, JJ, 1998)	0.3
"Although there is renewed enthusiasm for the use of digoxin in patients with heart failure, current dosing guidelines are based on a nomogram published in 1974."	( A case series of hospitalized patients with elevated digoxin levels. Fromm, L; Marik, PE, 1998)	0.8
" On the basis of the estimate of the dosing of digoxin these patients were divided into two groups: the first with therapeutic and the second with subtherapeutic concentrations of digoxin in serum."	( The level of plasma neuroendocrine activity and the concentration of digoxin in the serum of patients with mild chronic heart failure. Chmara, E; Jablecka, A; Korzeniowska, K, 1998)	0.79
" Causes of digoxin toxicity were worsening renal function (6 patients), excessive dosage prescribed (4 patients), excessive dosage self-administered (2 patients), multiple prescriptions (2 patients), accidental ingestion (1 patient), drug-drug interaction (1 patient) and unknown (1 patient)."	( Economic impact of digoxin toxicity. Bauman, JL; Gandhi, AJ; Morton, DJ; Vlasses, PH, 1997)	1.02
"05) number of dosage changes resulting in therapeutic serum drug levels than did the control group whose physicians received a report of serum drug level by itself."	( Evaluation of a computerized digoxin pharmacokinetic consultation service. Jeffrey, LP; Mahoney, CD; Pezzullo, JC; Rich, DS, 1981)	0.55
" When the audit categories of rational indication, correct performance, and appropriate dosage adjustment were evaluated independently, compliance rates were 66%, 73% and 86%, respectively."	( A utilization review of digoxin assays: sampling patterns and use. Bryant, SG; Doutre, WH; Fuchs, JE; Guernsey, BG; Hokanson, JA; Ingrim, NB; Sanders, AG, 1984)	0.57
" Digoxin concentrations in serum and urine samples collected for 48 hours after dosing were measured by fluorescence polarization immunoassay and radioimmunoassay, respectively."	( Bioavailability of digoxin tablets in healthy volunteers. Jones, DW; Lee, CH; Park, YJ; Sands, CD; Trang, JM, 1994)	1.53
"375 mg given twice on the day before the once daily dosing regimen started."	( The effect of bosentan on the pharmacokinetics of digoxin in healthy male subjects. Banken, L; Birnboeck, H; Nave, S; Schulz, R; Weber, C, 1999)	0.56
" Dose-response curves to iontophoresis of acetylcholine or norepinephrine were constructed at day 11."	( The local effects of systemic digoxin on the cutaneous microcirculation. Grossmann, M; Jamieson, MJ; Kirch, W, 1999)	0.59
" Spironolactone affected digoxin clearance and needs to be considered when dosing paediatric subjects."	( Population analysis for the optimization of digoxin treatment in Japanese paediatric patients. Higuchi, S; Minemoto, M; Suematsu, F; Yukawa, E, 1999)	0.87
" Misleading subtarget concentrations were repeatedly reported, and falsely guided drug dosing resulted in a case of digoxin intoxication."	( Intoxication due to negative canrenone interference in digoxin drug monitoring. Eber, B; Emmanuilidis, K; Müller, C; Steimer, W, 1999)	0.76
"0001), and plasma drug concentration at the end of a dosing interval (P = ."	( Pharmacokinetic interaction of digoxin with an herbal extract from St John's wort (Hypericum perforatum). Bauer, S; Brockmöller, J; Johne, A; Langheinrich, M; Maurer, A; Roots, I, 1999)	0.59
" Steady-state digoxin pharmacokinetics were not affected by multiple dosing with gemifloxacin."	( Lack of pharmacokinetic interaction between gemifloxacin and digoxin in healthy elderly volunteers. Allen, A; Ehren, N; Lewis, A; Vousden, M, )	0.73
" No direct drug-drug interactions were found in these studies, suggesting that repaglinide may be coprescribed with cimetidine, digoxin, or theophylline at the dosage used for monotherapy."	( Drug interaction studies with repaglinide: repaglinide on digoxin or theophylline pharmacokinetics and cimetidine on repaglinide pharmacokinetics. Hatorp, V; Thomsen, MS, 2000)	0.76
" Intervention-group physicians received academic detailing on the use and dosage of ACE inhibitors and angiotensin II-receptor inhibitors for CHF."	( Community pharmacist outreach program directed at physicians treating congestive heart failure. Brown, A; Miller, R; Parfrey, P; Ryan, K; Turner, CJ, 2000)	0.31
" However, truly individualized drug dosage regimens cannot be developed without first setting a specific individualized target goal, such as a target serum drug concentration, at a desired target time after the dose (usually at a peak or trough), for each patient."	( Goal-oriented, model-based drug regimens: setting individualized goals for each patient. Jelliffe, R, 2000)	0.31
"Plasma concentrations of digoxin after multiple administration at varying dosing schedules in Korean patients were used for population modeling."	( Population pharmacokinetics of digoxin in Korean patients. Derendorf, H; Jeon, S; Nagaraja, NV; Park, YJ; Sands, CD, 2000)	0.9
" Peak total digoxin serum concentrations post-Fab dosing were similar to the pre-Fab peak digoxin concentration for both Fab products (45 +/- 14 and 44 +/- 11 for DigiTAb, pre and post, respectively) 50 +/- 17 and 41 +/- 9 for Digibind, pre and post, respectively) indicating in vivo equimolar binding affinity."	( Comparison of the pharmacokinetics and in vivo bioaffinity of DigiTAb versus Digibind. Sjostrom, L; Ujhelyi, MR; Ward, SB, 2000)	0.69
" At steady state, cilomilast 15 mg BID had no significant effect on the steady-state pharmacokinetic parameters of digoxin, with 90% CIs for both primary end points--area under the plasma concentration-time curve (AUC) over a 24-hour dosing interval and minimum plasma concentration--completely contained within the specified interval for equivalence (0."	( Cilomilast: pharmacokinetic and pharmacodynamic interactions with digoxin. Clark, DJ; Collie, H; Kelly, J; Murdoch, RD; Schubert, C; Zussman, BD, 2001)	0.76
" Likewise, the predicted arithmetic mean steady-state peak concentration (C(SS,min)) and AUC at steady state during a dosing interval (AUC(SS,tau)) have a similar decrease."	( The effects of tegaserod (HTF 919) on the pharmacokinetics and pharmacodynamics of digoxin in healthy subjects. Appel-Dingemanse, S; Horowitz, A; Hubert, M; Ledford, PC; McLeod, JF; Osborne, S; Zhou, H, 2001)	0.54
"The estimated population parameter values may assist clinicians in the individualisation of digoxin dosage regimens."	( Population pharmacokinetics of digoxin in Japanese patients: a 2-compartment pharmacokinetic model. Aoyama, T; Goto, Y; Higuchi, S; Minemoto, M; Ohdo, S; Suematu, F; Yukawa, E; Yukawa, M, 2001)	0.82
" Tmax was statistically significantly shorter (54 min) following 08:00 dosing com pared to 20:00 dosing (96 min)."	( Morning-evening administration time differences in digoxin kinetics in healthy young subjects. Batu, OS; Erol, K; Kiliç, FS; Yildirim, E, 2001)	0.56
" Plasma tamsulosin concentrations were measured at regular intervals after dosing on day 15."	( Effects of the concomitant administration of tamsulosin (0.8 mg) on the pharmacokinetic and safety profile of intravenous digoxin (Lanoxin) in normal healthy subjects: a placebo-controlled evaluation. Forrest, A; Ito, Y; Kamimura, H; Miyazawa, Y; Paul Starkey, L; Schentag, JJ; Swarz, H, 2002)	0.52
" Not only may toxic concentrations remain unidentified, but intoxication could occur should dosage be increased because of falsely low results."	( Digoxin assays: frequent, substantial, and potentially dangerous interference by spironolactone, canrenone, and other steroids. Eber, B; Müller, C; Steimer, W, 2002)	1.76
" Optimal dosing will become increasingly difficult to judge."	( BNP in hormone-guided treatment of heart failure. Lainchbury, JG; Nicholls, MG; Richards, AM; Troughton, RW; Yandle, TG, )	0.13
" In practice, argatroban coadministered with these frequently prescribed drugs should require no dosage adjustments."	( Investigation of the interaction between argatroban and acetaminophen, lidocaine, or digoxin. DiCicco, RA; Graham, AM; Hursting, MJ; Inglis, AM; Sheth, SB; Tenero, DM, 2002)	0.54
" Taking simplicity in practical use into account, the clinical application of the proposed model will allow for accurate and rapid determination of the initial maintenance dosing regimen of digoxin based on the individual Ccr value, without actual measurement of its serum concentration."	( Predictive performance of serum digoxin concentration in patients with congestive heart failure by a hyperbolic model based on creatinine clearance. Chiba, M; Koida, M; Konishi, H; Minouchi, T; Shimizu, S; Yamaji, A, 2002)	0.79
" Subjects took erythromycin (800 mg per day) or clarithromycin (400 mg per day) on the day before digoxin dosing and during the kinetic study, Neither of the macrolides affected serum digoxin concentration-time curves."	( The effect of erythromycin and clarithromycin on the pharmacokinetics of intravenous digoxin in healthy volunteers. Kotegawa, T; Kuranari, M; Matsuki, S; Morimoto, T; Nakano, S; Otani, Y; Tsutsumi, K, 2002)	0.76
" The final model selected for the population prediction of digoxin clearance in pediatric patients was as follows: [equation: see text] Individual empirical Bayesian estimates were generated on the basis of the population estimates and were used to correlate the optimum dose of digoxin and patient age according to the following equation: [equation: see text] This equation and its derived nomogram may be used for the initial dosing of digoxin in children aged between 0 and 1 year."	( Population pharmacokinetics of digoxin in pediatric patients. Arranz, I; Falcao, AC; González, MC; Hernández, FJ; Lanao, JM; Martín-Suárez, A; Outeda, M; Quero, M, 2002)	0.84
"After subjects were dosed to steady state with digoxin, there were statistically significant reductions in QS(2) corrected for heart rate (QS(2)c) of 23 to 25 ms and heart rate of 4 to 6 beats/min."	( Teriparatide has no effect on the calcium-mediated pharmacodynamics of digoxin. Benson, CT; Voelker, JR, 2003)	0.81
" Our data indicate that a more aggressive dosing regimen of digoxin may be more effective in terms of heart rate reduction."	( Intravenously administered digoxin in patients with acute atrial fibrillation: a population pharmacokinetic/pharmacodynamic analysis based on the Digitalis in Acute Atrial Fibrillation trial. Held, P; Hornestam, B; Jerling, M; Karlsson, MO, 2003)	0.86
" There was no significant statistical difference in digoxin dosage between those with and those without digoxin toxicity."	( Digoxin toxicity in Thai medical patients: clinical manifestations and an appropriate diagnostic serum level. Jitapunkul, S; Kongsawat, V; Sutheparak, S, 2002)	2.01
" In the in vivo study, the kinetics of digoxin administered in single and multiple dosage regimens were compared in control rabbits and in rabbits treated simultaneously with acenocoumarol."	( Pharmacokinetic study of the digoxin-acenocoumarol interaction in rabbits. Alberca, I; Atencio, DR; Lanao, JM; Lopez, FG; Martin-Suarez, A; Mendez, ME; Santos, M; Zarzuelo, A, 2003)	0.88
" This suggests that both hawthorn and digoxin, in the doses and dosage form studied, may be coadministered safely."	( Interaction study between digoxin and a preparation of hawthorn (Crataegus oxyacantha). Aaronson, KD; Annesley, T; Bleske, BE; Smith, SG; Streetman, DS; Tamer, HR; Tankanow, R; Welton, JL, 2003)	0.89
" Digoxin administration according to the nationally recommended dosage and intervals unexpectedly resulted in serum levels in the toxic range."	( Immediate control of life-threatening digoxin intoxication in a child by use of digoxin-specific antibody fragments (Fab). Brock-Utne, JG; Farstad, M; Husby, P; Koller, ME; Lund, T; Ohm, OJ; Segadal, L, 2003)	1.5
" Thus, aprepitant, when dosed as a 5-day regimen, did not interact with a known substrate of the P-glycoprotein transporter."	( Lack of effect of aprepitant on digoxin pharmacokinetics in healthy subjects. Brackett, LE; De Smet, M; Feuring, M; Goldberg, MR; Gottesdiener, KM; Hesney, M; Lee, Y; Majumdar, AK; Michiels, N; Murphy, MG; Orlowski, LH; Petty, KJ; Wehling, M, 2003)	0.6
" Sex, age, and dosage had no significant effect in the suspicion or confirmation of digoxin intoxication."	( [Confirmed and suspected digoxin intoxications]. Abadín Delgado, JA; Durán Quintana, JA; Jiménez Plata, C; Máiquez Asuero, P; Sánchez Romero, A, 2003)	0.85
"Tween 80 (Polysorbate 80) is a hydrophilic nonionic surfactant commonly used as an ingredient in dosing vehicles for pre-clinical in vivo studies (e."	( Commonly used surfactant, Tween 80, improves absorption of P-glycoprotein substrate, digoxin, in rats. Chong, S; Morrison, RA; Yao, M; Zhang, H, 2003)	0.54
" Digoxin is insoluble in water, sensitive to light and is a subject of acidic hydrolysis, it is a challenge to the technologists of parenteral dosage forms."	( Study of insolubility problems of dexamethasone and digoxin: cyclodextrin complexation. Dilova, V; Filcheva, K; Grigorova, P; Pavlova, A; Spirova, N; Zlatarova, V, )	1.29
" Dosage schemes in use at the Cardiology Service produced the following results: 40."	( Pharmacokinetics of digoxin in children with congestive heart failure aggravated by other diseases. Bobadilla-Chávez, J; Flores-Pérez, J; Juárez-Olguín, H; Lares-Asseff, I, )	0.45
"The range of dosage required in order to adjust individual treatments was very wide, leading us to the conclusion that therapeutic schemes for this population should be individualized based on their pharmacokinetic parameters, and therapeutic monitoring of drugs should be performed."	( Pharmacokinetics of digoxin in children with congestive heart failure aggravated by other diseases. Bobadilla-Chávez, J; Flores-Pérez, J; Juárez-Olguín, H; Lares-Asseff, I, )	0.45
"3), a reduction in digoxin maximal plasma concentration (C(max)) of -37% (95% CI, -42 to -32), and a reduction in digoxin plasma concentration at 24 hours after previous dosing (C(trough)) of -19% (95% CI, -27 to -11)."	( Effect of St John's wort dose and preparations on the pharmacokinetics of digoxin. Drewelow, B; Frank, B; Hehl, EM; Majcher-Peszynska, J; Mueller, SC; Petzsch, M; Riethling, AK; Sievers, H; Uehleke, B; Woehling, H, 2004)	0.88
" Dosage of digoxin was increased in 2 other patients with continuous treatment by the column."	( Beta2-microglobulin adsorption column reduces digoxin trough level during hemodialysis: three case reports. Ando, H; Fujimura, A; Saito, T; Tsuruoka, S; Wakaumi, M; Yamamoto, H, 2004)	0.97
" In conclusion, there is no clinically relevant interaction between etanercept and digoxin, and both drugs can be safely coadministered without the need for a dosage adjustment."	( Absence of a clinically relevant interaction between etanercept and digoxin. Korth-Bradley, J; Le Coz, F; Parks, V; Patat, A; Simcoe, D; Zhou, H, 2004)	0.78
" Studies are required to determine safe and effective digoxin dosing regimens for frail elderly heart failure patients."	( Digoxin prescribing for heart failure in elderly residents of long-term care facilities. Flett, N; Heckman, GA; McKelvie, RS; Merali, F; Misiaszek, B; Patterson, CJ; Turpie, ID, 2005)	2.02
" A drug that causes particular problems with drug dosing in primary care is digoxin because of its narrow therapeutic range and low therapeutic index."	( Assessing the accuracy of a computerized decision support system for digoxin dosing in primary care: an observational study. Avery, AJ; Brown, NS; Hippisley-Cox, J; Horsfield, P; Howard, R; Kroese, WL; Savelyich, BS; Schers, H, 2005)	0.79
" Exenatide administration does not cause any changes in digoxin steady-state pharmacokinetics that would be expected to have clinical sequelae; thus, dosage adjustment does not appear warranted, based on pharmacokinetic considerations."	( Effect of exenatide on the steady-state pharmacokinetics of digoxin. Chan, C; Kothare, PA; Lim, M; Linnebjerg, H; Mace, KF; Park, S; Soon, DK; Wise, SD; Yeo, A, 2005)	0.82
" The present study compared the quality of life of congestive heart failure patients on one year follow-up period with two different dosing of digoxin (5/7 therapy and 7/7 therapy in whom the target serum digoxin concentration is maintained)."	( Comparison of target concentration intervention strategy with conventional dosing of digoxin. Anbalagan, M; Muralidharan, TR; Rajendran, SD; Rao, YM; Thanikachalam, S, )	0.56
"0125 mg/kg/day, which is within the recommended oral maintenance dosage range for dogs, was administered orally for 2 weeks."	( Detection of cone dysfunction induced by digoxin in dogs by multicolor electroretinography. Itoh, N; Izumisawa, Y; Kotani, T; Kushiro, T; Maehara, S; Osawa, A; Seno, T; Tsuzuki, K; Wakaiki, S; Yamashita, K, )	0.4
" Yet, in the modern era the incidence of digoxin toxicity has been declining for a variety of reasons, including a new (lower) therapeutic range, the development of more effective drug therapies for heart failure, and more accurate dosing methods."	( Mechanisms, manifestations, and management of digoxin toxicity in the modern era. Bauman, JL; Didomenico, RJ; Galanter, WL, 2006)	0.86
" Although further study is required to verify that the DLIS implicated was indeed the interfering species, it does again highlight the importance of careful method selection in the clinical therapeutic drug monitoring laboratory to ensure that such well-established potential problems do not result in inappropriate dosage reduction with consequent lack of adequate drug exposure and serious clinical sequelae."	( Suspected DLIS interference in the dimension DGNA digoxin assay method and the clinical application of the revised digoxin target range. Goldsworthy, SJ; Ho, H; Horowitz, JD; Jones, TE; Morris, RG; Wagner, TJ, 2006)	0.59
"The adjuvant treatment of KLJ on the basis of Western conventional therapy can significantly improve CHF patients' exercise tolerance, quality of life and cardiac function, reduce the dosage of diuretic and digoxin needed, and decrease the re-admission frequency due to aggravation of heart failure."	( Effects of Kanlijian on exercise tolerance, quality of life, and frequency of heart failure aggravation in patients with chronic heart failure. Jiang, MX; Ruan, XF; Xu, Y, 2006)	0.52
" Subjects received warfarin on the 10th day of 16 days of dosing with either solifenacin or placebo."	( Multiple doses of the antimuscarinic agent solifenacin do not affect the pharmacodynamics or pharmacokinetics of warfarin or the steady-state pharmacokinetics of digoxin in healthy subjects. Krauwinkel, WJ; Kuipers, ME; Smulders, RA, 2006)	0.53
"Since the pharmacokinetics and pharmacodynamics of a single dose of warfarin and the steady-state pharmacokinetics of digoxin were not affected by coadministration of solifenacin in healthy subjects, the need for dosing adjustments for digoxin and/or warfarin does not seem warranted."	( Multiple doses of the antimuscarinic agent solifenacin do not affect the pharmacodynamics or pharmacokinetics of warfarin or the steady-state pharmacokinetics of digoxin in healthy subjects. Krauwinkel, WJ; Kuipers, ME; Smulders, RA, 2006)	0.74
"Because rifampin (RIF) induces hepatic enzymes and inhibits uptake transporters, dosing a drug that is a dual substrate of enzymes and uptake transporters on the final day of an inducing regimen should exhibit less inductive effect than dosing on the following day in the absence of RIF, since RIF decreases drug uptake into liver."	( Elucidating the effect of final-day dosing of rifampin in induction studies on hepatic drug disposition and metabolism. Benet, LZ; Lam, JL; Okochi, H; Shugarts, SB, 2006)	0.33
" However, dosing methods have not been modified to reflect this change."	( A method of determining the dose of digoxin for heart failure in the modern era. Bauman, JL; DiDomenico, RJ; Fitch, M; Viana, M, )	0.41
" The proposed method was then used to create a dosing nomogram."	( A method of determining the dose of digoxin for heart failure in the modern era. Bauman, JL; DiDomenico, RJ; Fitch, M; Viana, M, )	0.41
"Because the new therapeutic window of digoxin is associated with improved outcomes, more intensive dosage refinement should be considered."	( A method of determining the dose of digoxin for heart failure in the modern era. Bauman, JL; DiDomenico, RJ; Fitch, M; Viana, M, )	0.68
" When a loading dose of oral amiodarone is required in a patient receiving digoxin, the digoxin dosage should first be reduced, and digoxin therapy should be adjusted based on signs and symptoms of digoxin toxicity."	( Plasma digoxin concentration fluctuations associated with timing of plasma sampling and amiodarone administration. DeVore, KJ; Hobbs, RA, 2007)	1.02
" The aim of this study was to determine whether appropriate dosage adjustments were made for drugs that are nephrotoxic, excreted, or metabolized (TEM medications) by the kidney in patients with renal impairment."	( Medication dosing errors in hospitalized patients with renal impairment: a study in Palestine. Abu-Taha, AS; Al-Jabi, SW; Janem, SA; Jaradat, NA; Sabri, IA; Sawalha, AF; Sweileh, WM; Zaid, AA; Zyoud, SH, 2007)	0.34
" Evaluation of appropriate dosing was based on Physician Disk Reference (PDR)."	( Medication dosing errors in hospitalized patients with renal impairment: a study in Palestine. Abu-Taha, AS; Al-Jabi, SW; Janem, SA; Jaradat, NA; Sabri, IA; Sawalha, AF; Sweileh, WM; Zaid, AA; Zyoud, SH, 2007)	0.34
" Dosage adjustment was necessary for 193 TEM medications."	( Medication dosing errors in hospitalized patients with renal impairment: a study in Palestine. Abu-Taha, AS; Al-Jabi, SW; Janem, SA; Jaradat, NA; Sabri, IA; Sawalha, AF; Sweileh, WM; Zaid, AA; Zyoud, SH, 2007)	0.34
"In our study, a wide range of dosing errors was common among patients with renal impairment that was common during hospitalization."	( Medication dosing errors in hospitalized patients with renal impairment: a study in Palestine. Abu-Taha, AS; Al-Jabi, SW; Janem, SA; Jaradat, NA; Sabri, IA; Sawalha, AF; Sweileh, WM; Zaid, AA; Zyoud, SH, 2007)	0.34
"4% in rats, with non-linear pharmacokinetics when its dosage increased."	( Role of P-glycoprotein in the intestinal absorption of tanshinone IIA, a major active ingredient in the root of Salvia miltiorrhiza Bunge. Chen, X; Chowbay, B; Duan, W; Li, CG; Liang, J; Lin, SG; Liu, PQ; Wen, JY; Yu, XY; Zhou, SF; Zhou, ZW, 2007)	0.34
" Therefore, their interchangeable use cannot be advocated in the dosing of medications until further prospective validations are performed."	( Use of GFR equations to adjust drug doses in an elderly multi-ethnic group--a cautionary tale. Djurdjev, O; Gill, J; Levin, A; Malyuk, R, 2007)	0.34
" However, the digoxin dosage regimen for the individual patient should be based on a careful appraisal of their clinical need for the drug."	( Population pharmacokinetic investigation of digoxin in Japanese neonates. Akiyama, K; Minemoto, M; Suematsu, F; Yukawa, E; Yukawa, M, 2007)	0.96
" Seven healthy volunteers were dosed with carbamazepine over 16 consecutive days."	( Pharmacodynamics of carbamazepine-mediated induction of CYP3A4, CYP1A2, and Pgp as assessed by probe substrates midazolam, caffeine, and digoxin. Cederberg, J; Dahl, ML; Karlsson, MO; Magnusson, MO; Sandström, R, 2008)	0.55
" We build upon our previous findings and generated a simple index for the adequate administration dosage of beta-methyldigoxin based on variable degrees of renal function and the serum trough level of beta-methyldigoxin."	( [Pharmaceutical support in the cardiovascular and cardiovascular surgery ward]. Kataoka, Y; Machida, S; Masuda, K, 2007)	0.55
" The sitagliptin dosage recommended by the manufacturer is 100 mg once daily as monotherapy or in combination with metformin or a thiazolidinedione."	( Sitagliptin: a novel agent for the management of type 2 diabetes mellitus. Nogid, A; Pham, DQ; Plakogiannis, R, 2008)	0.35
" To optimize dosing of digoxin, therapeutic drug monitoring has been important since assays became available in the 1970s."	( Discordant results from "real-world" patient samples assayed for digoxin. Jones, TE; Morris, RG, 2008)	0.89
"Thirty-six digoxin samples were assayed; in 39% of these, digoxin concentrations were discordant and different dosage adjustments would have followed."	( Discordant results from "real-world" patient samples assayed for digoxin. Jones, TE; Morris, RG, 2008)	0.97
" Following a 10-day wash out, they started a 19-day taranabant dosing regimen (6 mg once daily from day -14 to day 5) designed to establish and maintain steady-state levels of taranabant."	( Pharmacokinetics of digoxin in healthy subjects receiving taranabant, a novel cannabinoid-1 receptor inverse agonist. Denker, AE; Dunbar, S; Lewis, NM; Li, S; Morelli, G; Taggart, W; Vessey, LK; Wagner, JA; Yuan, J, 2009)	0.68
"Digoxin overdose is closely related to Chronic Kidney Disease and creatinine dosage adjustment is usually needed."	( [Use of MDRD equation to detect occult renal failure and reduce the risk of digitalis overdose]. Cepeda Piorno, J; Fernández Rodríguez, E; González García, ME; Pobes Martínez de Salinas, A, 2009)	1.8
" Significant differences were observed in over dosage between high creatinine group regarding to normal creatinine group (31% vs."	( [Use of MDRD equation to detect occult renal failure and reduce the risk of digitalis overdose]. Cepeda Piorno, J; Fernández Rodríguez, E; González García, ME; Pobes Martínez de Salinas, A, 2009)	0.35
"For GFR lower than 60 mL/min, the high interindividual variation of the digoxin total CL found among patients with similar renal function is an important limiting factor in the prediction of digoxin dosage regimens."	( Glomerular filtration rate estimation using the Cockcroft-Gault and modification of diet in renal disease formulas for digoxin dose adjustment in patients with heart failure. Bouzas, L; Tutor, JC; Vazquez-Hernandez, M, 2009)	0.79
" The cardiotonic steroids ouabain, digoxin, and marinobufagenin all show an inverted U-shaped dose-response curve with inhibition of pumping at concentrations near their IC(50), while increasing Na/K ATPase activity at doses below their IC(50)."	( Low-dose cardiotonic steroids increase sodium-potassium ATPase activity that protects hippocampal slice cultures from experimental ischemia. Bergold, PJ; Oselkin, M; Tian, D, 2010)	0.64
"This simple final population model of Vd and CL can be used in clinical practice for estimating appropriate dosage regimen of loading dose and maintenance dose, respectively."	( Population pharmacokinetics of digoxin in Thai pediatric patients. Petcharattana, S; Preechagoon, Y; Somsaard, P, 2009)	0.64
" The manufacturer's recommended dosing scheme was modified, with 80 mg Fab administered intravenously within 15 minutes followed by a continuous infusion at 30 mg/h."	( Free and total digoxin in serum during treatment of acute digoxin poisoning with Fab fragments: case study. Eyer, F; Müller, C; Steimer, W; Zilker, T, 2010)	0.71
"In general, the accuracy of medication dosage devices seems to be most affected by viscosity of the liquid being measured."	( Accuracy and precision of manufacturer-supplied liquid medication administration devices before and after patient education. Parnapy, S; Peacock, G; Raynor, S; Wetmore, S, )	0.13
"Compared to fixed-dose single-vial drug administration in adults, pediatric drug dosing and administration requires a series of calculations, all of which are potentially error prone."	( Comparing errors in ED computer-assisted vs conventional pediatric drug dosing and administration. Kanemori, J; Yamamoto, L, 2010)	0.36
" Each part consisted of a set of medication administration and/or dosing tasks."	( Comparing errors in ED computer-assisted vs conventional pediatric drug dosing and administration. Kanemori, J; Yamamoto, L, 2010)	0.36
" However, the digoxin dosage regimen for the individual patient should be based on a careful appraisal of his or her clinical need for the drug."	( Population pharmacokinetic investigation of digoxin in Japanese infants and young children. Aki, H; Ikeda, H; Mimemoto, M; Suematsu, F; Takiguchi, T; Yukawa, E; Yukawa, M, 2011)	0.99
" The dosage was calculated with the Konishi equation."	( Individual dosage of digoxin in patients with heart failure. Brunner-La Rocca, H; Foglia, P; Mombelli, G; Moschovitis, G; Muzzarelli, S; Pfister, O; Stricker, H, 2011)	0.69
"This study supports the clinical validity of the Konishi equation for calculating individual digoxin dosage in Caucasians, targeting SDCs according to current HF guidelines."	( Individual dosage of digoxin in patients with heart failure. Brunner-La Rocca, H; Foglia, P; Mombelli, G; Moschovitis, G; Muzzarelli, S; Pfister, O; Stricker, H, 2011)	0.91
" A clinical study was performed and the plasma pharmacokinetics [observed maximum plasma drug concentration (C(max)) and area under the plasma concentration versus time curve from 0 to 72 h postdose (AUC(0-72 h))] of orally dosed digoxin (0."	( The utility of in vitro data in making accurate predictions of human P-glycoprotein-mediated drug-drug interactions: a case study for AZD5672. Butters, C; Elsby, R; Gillen, M; Imisson, G; Sharma, P; Smith, V; Surry, DD, 2011)	0.55
" Moreover, the release properties of the dosage form should be known."	( In vivo probes of drug transport: commonly used probe drugs to assess function of intestinal P-glycoprotein (ABCB1) in humans. Oswald, S; Siegmund, W; Terhaag, B, 2011)	0.37
" Rifampin's effect on the AUC(0-3 h) of digoxin was biphasic: the AUC(0-3 h) increased with concomitant dosing of the two drugs but decreased when digoxin was administered after rifampin."	( Rifampin's acute inhibitory and chronic inductive drug interactions: experimental and model-based approaches to drug-drug interaction trial design. Cai, X; Chu, X; Ding, Y; Evers, R; Gibson, C; Reitman, ML; Roupe, K; Stoch, A; Stone, JA; Venkatasubramanian, R; Wagner, JA; Witter, R; Yabut, J; Zajic, S, 2011)	0.64
" Dosage adjustment according to renal function is indicated for many drugs, in order to avoid adverse reactions of medications and/or aggravation of renal impairment."	( The assessment of renal function in relation to the use of drugs in elderly in nursing homes; a cohort study. Lannering, C; Midlöv, P; Modig, S; Mölstad, S; Ostgren, CJ, 2011)	0.37
" The elderly have reduced elimination of digoxin, so if digoxin is to be used, the dosing strategy must be conservative and therapeutic monitoring is needed."	( Use of digoxin for heart failure and atrial fibrillation in elderly patients. Cheng, JW; Rybak, I, 2010)	1.08
"During the study period, there were 13 fatalities (cases) and 13 survivors (controls), of whom seven cases and five controls received appropriately dosed digoxin-specific antibody Fab fragments (Fab)."	( Prognostic utility of serum potassium in chronic digoxin toxicity: a case-control study. Hoffman, RS; Manini, AF; Nelson, LS, 2011)	0.82
" We proposed a systematic classification scheme using FDA-approved drug labeling to assess the DILI potential of drugs, which yielded a benchmark dataset with 287 drugs representing a wide range of therapeutic categories and daily dosage amounts."	( FDA-approved drug labeling for the study of drug-induced liver injury. Chen, M; Fang, H; Liu, Z; Shi, Q; Tong, W; Vijay, V, 2011)	0.37
" Exposure to dabigatran was not significantly altered with concomitant digoxin-the maximum concentration (Cmax,ss ) and area under the concentration-time curve at steady state over 1 dosing interval (AUCτ,ss ) of dabigatran with and without digoxin were essentially unchanged."	( Pharmacokinetics and pharmacodynamics of dabigatran etexilate, an oral direct thrombin inhibitor, with coadministration of digoxin. Körnicke, T; Rathgen, K; Reseski, K; Roth, W; Stähle, H; Stangier, J, 2012)	0.82
"Inappropriate doses and high serum concentrations of digoxin are highly prevalent in patients with renal impairment, and the drug dosage adjustment according to the glomerular filtration rate (GFR) is recommended."	( Diagnostic accuracy of a hyperbolic model in predicting digoxin concentrations based on glomerular filtration rates. González-López, J; Tutor, JC, 2011)	0.87
"The diagnostic efficiency obtained in the prediction of serum digoxin concentrations from estimated GFR values is unacceptable for the drug dosage adjustment in clinical practice."	( Diagnostic accuracy of a hyperbolic model in predicting digoxin concentrations based on glomerular filtration rates. González-López, J; Tutor, JC, 2011)	0.86
"We developed a new model for elderly patient dosing of digoxin with good predictive performance."	( Determination of digoxin clearance in Japanese elderly patients for optimization of drug therapy: a population pharmacokinetics analysis using nonlinear mixed-effects modelling. Aki, H; Ikeda, H; Mimemoto, M; Suematsu, F; Takiguchi, T; Yukawa, E; Yukawa, M, 2011)	0.96
" Digoxin dosing based on patient-specific factors such as age, lean body weight, and renal function will allow practitioners to minimize drug toxicity while maintaining clinical efficacy."	( Digoxin: clinical highlights: a review of digoxin and its use in contemporary medicine. Ehle, M; Giugliano, RP; Patel, C, 2011)	2.72
" Thus, no dosage adjustment for digoxin is necessary when co-administered with anacetrapib."	( Lack of an effect of anacetrapib on the pharmacokinetics of digoxin in healthy subjects. Ali, M; Connolly, SM; DeGroot, B; Garg, A; Gendrano, IN; Krishna, R; Li, S; Liu, Y; Maes, A; Stoch, SA; Stypinski, D; Wagner, JA, 2011)	0.9
"6%); assessment of dosage change 5 (5."	( Assessment of the appropriateness of serum digoxin concentration measurement in a medical group setting. Orrico, KB; Wilson, AR; Wu, M, 2011)	0.63
" A dose-response relationship exists with regards to PTQ-changes (a quantitative measure of ECG-changes)."	( Digoxin concentrations in serum and saliva: relationship to ECG changes and dosage in healthy volunteers. Aucamp, BN; Joubert, PH; Müller, FO, 1976)	1.7
" This case report describes a novel approach to fetal cardioversion using oral maternal bolus dosing of flecainide."	( A novel method of fetal cardioversion. Sanghavi, DM, 2013)	0.39
" Results showed that 20(S)-Rh2 enhanced the oral absorption of digoxin in rats in a dose-dependent manner; 20(R)-Rh2 at low dosage increased the oral absorption of digoxin, but this effect diminished with elevated dosage of 20(R)-Rh2."	( Stereoselective regulations of P-glycoprotein by ginsenoside Rh2 epimers and the potential mechanisms from the view of pharmacokinetics. Lu, M; Niu, F; Sun, J; Wang, G; Wu, X; Zhang, J; Zhou, F, 2012)	0.62
" They also permit maximally precise dosage regimens to be developed for patients using multiple model dosage design, something parametric modeling methods cannot do."	( Some comments and suggestions concerning population pharmacokinetic modeling, especially of digoxin, and its relation to clinical therapy. Jelliffe, RW, 2012)	0.6
"Therapeutic drug monitoring is an integral part of services offered by toxicology laboratories because certain drugs require routine monitoring for dosage adjustment to achieve optimal therapeutic response and avoid adverse drug reactions."	( Impact of interferences including metabolite crossreactivity on therapeutic drug monitoring results. Dasgupta, A, 2012)	0.38
" In the present study, a digoxin dose-response curve was conducted to observe the effects on naloxone-precipitated withdrawal and locomotor activity in mice."	( A comparison of the effects of digoxin, ouabain and milrinone on naloxone-precipitated withdrawal syndrome in mice. Bai, YL; Chen, YY; Chu, QJ; Li, J; Li, WJ; Zhang, Q, 2012)	0.97
" Its therapeutic window is narrow, with effect dosage very close to the toxic dosage."	( Anti-digoxin Fab variants generated by phage display. Kalil, J; Moro, AM; Murata, VM; Schmidt, MC; Tsuruta, LR, 2013)	0.9
"97) or ramipril (AUC over a uniform dosing interval τ at steady state [AUCτ,ss]: GMR, 96."	( Lack of clinically relevant drug-drug interaction between empagliflozin, a sodium glucose cotransporter 2 inhibitor, and verapamil, ramipril, or digoxin in healthy volunteers. Broedl, UC; Macha, S; Pinnetti, S; Rose, P; Schoene, K; Sennewald, R; Woerle, HJ, 2013)	0.59
"The Biopharmaceutics Drug Disposition Classification System (BDDCS) predicts intestinal transporter effects to be clinically insignificant following oral dosing for highly soluble and highly permeable/metabolized drugs (class 1 drugs)."	( Effect of P-glycoprotein on the rat intestinal permeability and metabolism of the BDDCS class 1 drug verapamil. Benet, LZ; Estudante, M; Maya, M; Morais, JG; Soveral, G, 2013)	0.39
"25 mg a day dosage (P = ."	( Digoxin and 30-day all-cause hospital admission in older patients with chronic diastolic heart failure. Ahmed, A; Allman, RM; Bourge, RC; Cutter, GR; Elbaz, S; Fleg, JL; Fonarow, GC; Hashim, T; McGwin, G; Morgan, CJ; Patel, K; Prabhu, SD; Zile, MR, 2014)	1.85
" The selected compounds differed by the slopes of their dose-response curve: compounds with a slope of 1 (GCV) representing one target or noncooperativity and compounds with high slopes indicating positive cooperativity."	( In vitro combination of anti-cytomegalovirus compounds acting through different targets: role of the slope parameter and insights into mechanisms of Action. Arav-Boger, R; Cai, H; Forman, M; He, R; Kapoor, A; Posner, GH; Venkatadri, R, 2014)	0.4
" In this way, the parameter distributions became discrete rather than continuous, suitable for use in developing maximally precise digoxin dosage regimens, individualized to an adult patient's age, gender, body weight, and renal function, to achieve desired specific target goals either in the central (serum) compartment or in the peripheral (effect) compartment using the method of multiple model dosage design."	( A two-compartment population pharmacokinetic-pharmacodynamic model of digoxin in adults, with implications for dosage. Bayard, D; Jelliffe, RW; Milman, M; Schumitzky, A; Van Guilder, M, 2014)	0.84
" Second, a strong association has emerged between serum concentration and the safety and efficacy of digoxin, which indicates a change in our approach to dosing this agent is needed."	( A perspective on re-evaluating digoxin's role in the current management of patients with chronic systolic heart failure: targeting serum concentration to reduce hospitalization and improve safety profile. Adams, KF; Bauman, JL; Butler, J; Ghali, JK; Herbert Patterson, J; Mackowiak, JI; Sabbah, H; Stough, WG; van Veldhuisen, DJ; Ventura, HO, 2014)	0.9
" The steady-state area under concentration-time curve over the dosing interval (AUC(24,ss)) and maximum steady-state plasma concentration (C(max,ss)) of digoxin were measured; ratios of these parameters for co-administration of digoxin + lacosamide versus digoxin alone were used to evaluate potential DDIs."	( Effect of lacosamide on the steady-state pharmacokinetics of digoxin: results from a phase I, multiple-dose, double-blind, randomised, placebo-controlled, crossover trial. Andreas, JO; Cawello, W; Mueller-Voessing, C, 2014)	0.84
" Dosage regimens achieved ≤11 ng/g in the model's peripheral compartment."	( The role of digitalis pharmacokinetics in converting atrial fibrillation and flutter to regular sinus rhythm. Jelliffe, RW, 2014)	0.4
" Therefore, sucroferric oxyhydroxide may be administered concomitantly without the need to adjust the dosage regimens of these drugs."	( Drug-drug interactions between sucroferric oxyhydroxide and losartan, furosemide, omeprazole, digoxin and warfarin in healthy subjects. Chong, E; Kalia, V; Willsie, S; Winkle, P, 2014)	0.62
"To review the pharmacology, efficacy, effectiveness, indications, safety and the dosage of digoxin-specific antibody fragments."	( Digoxin-specific antibody fragments in the treatment of digoxin toxicity. Buckley, NA; Chan, BS, )	1.79
" The lowest effective digoxin-Fab dosing regimen has not been established."	( Digoxin-specific antibody fragments in the treatment of digoxin toxicity. Buckley, NA; Chan, BS, )	1.89
"The results of this study indicate that clearance of digoxin and the creatinine clearance rate cannot be explained by renal function alone and that the validity of the Konishi equation for individualizing the digoxin dosage in Chinese patients is limited, being applicable only in stage 3 renal disease."	( Efficiency of individual dosage of digoxin with calculated concentration. Li, P; Qin, W; Wang, X; Yang, P; Zhang, X; Zhao, L, 2014)	0.93
"9 ng/ml, by using a simplified nomogram to individualize digoxin dosing with standard dosing practices in patients with heart failure, and to characterize the relationship between genetic polymorphisms of the ABCB1 gene and SDC."	( Use of a simplified nomogram to individualize digoxin dosing versus standard dosing practices in patients with heart failure. Bauman, JL; Bishop, JR; Bress, AP; Deyo, KL; DiDomenico, RJ; Groo, VL; Na-Thalang, K; Patel, SR; Tsao, YY, 2014)	0.91
"Digoxin doses were determined either by the dosing nomogram (65 patients) or standard care (SC; 66 patients) by using historical controls who were randomly selected from a list of SDCs obtained from laboratory records and who had their digoxin doses determined by standard dosing practices."	( Use of a simplified nomogram to individualize digoxin dosing versus standard dosing practices in patients with heart failure. Bauman, JL; Bishop, JR; Bress, AP; Deyo, KL; DiDomenico, RJ; Groo, VL; Na-Thalang, K; Patel, SR; Tsao, YY, 2014)	2.1
" Postdistributive steady-state SDCs were measured 2-4 weeks after digoxin dosage adjustment or initiation."	( Use of a simplified nomogram to individualize digoxin dosing versus standard dosing practices in patients with heart failure. Bauman, JL; Bishop, JR; Bress, AP; Deyo, KL; DiDomenico, RJ; Groo, VL; Na-Thalang, K; Patel, SR; Tsao, YY, 2014)	0.9
"Our simplified digoxin dosing nomogram resulted in lower SDCs compared with standard dosing practices but achieved therapeutic SDCs with similar frequency."	( Use of a simplified nomogram to individualize digoxin dosing versus standard dosing practices in patients with heart failure. Bauman, JL; Bishop, JR; Bress, AP; Deyo, KL; DiDomenico, RJ; Groo, VL; Na-Thalang, K; Patel, SR; Tsao, YY, 2014)	1.01
" They show an inverted U-shaped dose-response curve with inhibition of pumping at high concentrations while increasing NKA activity at low concentrations."	( Why Whip the Starving Horse When There Are Oats for the Starving Myocardium? Fürstenwerth, H, )	0.13
" There is a standardized formula to calculate appropriate Fab fragment dosage based on the serum digoxin concentration."	( Assessment of Digoxin-Specific Fab Fragment Dosages in Digoxin Poisoning. Cantrell, FL; Clark, RF; Machado, C; Nordt, SP, )	0.71
" Efforts should be made to evaluate the impact of CysC in special populations in order to define its clinical value in dosing optimization."	( Cystatin C as a potential biomarker for dosing of renally excreted drugs. Brou, NA; Jacqz-Aigrain, E; Zhao, W, 2015)	0.42
" Dosing of this therapy for chronic and acute poisonings is based on the steady-state serum concentrations of digoxin, historical data in acute ingestions, or empiric regimens purportedly based on the average requirements."	( Digoxin-Specific Antibody Fragment Dosing: A Case Series. Aks, SE; Bryant, SM; Chhabra, N; Valento, M, )	1.79
"To show the advantages of therapeutic drug monitoring for dosing of digoxin."	( [Personalized pharmacotherapy of digoxin]. Grundmann, M; Kacířová, I, 2015)	0.93
" The aim of this study was to assess whether appropriate dosage adjustments were made in hospitalized patients with renal impairment."	( Drug dosage adjustment in hospitalized patients with renal impairment at Tikur Anbessa specialized hospital, Addis Ababa, Ethiopia. Getachew, H; Shibeshi, W; Tadesse, Y, 2015)	0.42
" Data regarding serum creatinine level, age, sex and prescribed drugs and their dosage was collected from the patients' medical records."	( Drug dosage adjustment in hospitalized patients with renal impairment at Tikur Anbessa specialized hospital, Addis Ababa, Ethiopia. Getachew, H; Shibeshi, W; Tadesse, Y, 2015)	0.42
"The findings indicate that dosing errors were common among hospitalized patients with renal impairment."	( Drug dosage adjustment in hospitalized patients with renal impairment at Tikur Anbessa specialized hospital, Addis Ababa, Ethiopia. Getachew, H; Shibeshi, W; Tadesse, Y, 2015)	0.42
" In the clinical study, when digoxin was co-administered with fostamatinib, digoxin levels were higher before dosing and throughout the dosing interval, and an increase in exposure to digoxin was observed."	( Effects of Fostamatinib on the Pharmacokinetics of Digoxin (a P-Glycoprotein Substrate): Results From in Vitro and Phase I Clinical Studies. Baluom, M; Brealey, C; Elsby, R; Gillen, M; Lau, D; Mant, T; Martin, P; Millson, D; Oliver, S, 2015)	0.96
" Ctrough versus area under the plasma concentration versus time curve in a dosing interval of 24 hours (AUC0-24h) and Cmax versus AUC0-24h for digoxin were established by linear regression."	( Strategy for the Prediction of Steady-State Exposure of Digoxin to Determine Drug-Drug Interaction Potential of Digoxin With Other Drugs in Digitalization Therapy. Srinivas, NR, )	0.58
" A linear regression relating the patient's SDC, maintenance dose of digoxin and the HUGE value was estimated to generate a dosage equation."	( A New Method for Individualized Digoxin Dosing in Elderly Patients. Ardanuy Albajar, R; Calvo Hernández, MV; García González, D; Macías Núñez, JF; Martin-Suarez, A, 2016)	0.95
"We offer a new validated digoxin dosing equation for elderly patients."	( A New Method for Individualized Digoxin Dosing in Elderly Patients. Ardanuy Albajar, R; Calvo Hernández, MV; García González, D; Macías Núñez, JF; Martin-Suarez, A, 2016)	1.02
"7 ng/mL when dosing digoxin in patients with heart failure and reduced EF."	( Dose response characterization of the association of serum digoxin concentration with mortality outcomes in the Digitalis Investigation Group trial. Adams, KF; Bauman, JL; Butler, J; Gattis Stough, W; Ghali, JK; Mackowiak, JI; Patterson, JH; Sabbah, H; Schwartz, TA; van Veldhuisen, DJ; Ventura, HO, 2016)	1
"The focus of this review is on cardiac and non-cardiac effects of digoxin, a drug used for treating the heart failure, and on link between these effects and the serum digoxin concentration (SDC) in different dosing regimens."	( [Digoxin in elderly patients: therapeutic drug monitoring to increase the efficiency of therapy (a review)]. Akhmedov, TA; Pushkin, AS; Rukavishnikova, SA; Yakovlev, AA; Zadvor'ev, SF, 2016)	1.58
"Despite the small population, these parameters could be used as a guide to calculate the initial dosage requirements in the third trimester of pregnancy for treating fetal SVT."	( Pharmacokinetics and dosing requirements of digoxin in pregnant women treated for fetal supraventricular tachycardia. Calvo, MV; Garcia-Cuenllas Alvarez, L; Lanao, JM; Martin-Suarez, A; Medina-Barajas, F; Pérez-Blanco, JS; Sanchez-Hernandez, JG, 2017)	0.72
"3%) patients for low dosing with CSD<0."	( Pharmacokinetic monitoring of chronic treatment with digoxin from Primary Health Care. García-Iranzo, EM; García-Monsalve, A; Matoses-Chirivella, C; Murcia-López, AC; Navarro-Ruiz, A; Rodríguez-Lucena, FJ, 2017)	0.7
"Being a narrow therapeutic index drug, digoxin may cause harm if dosed without regular measurements of serum levels."	( THE POSOLOGY AND TROUGH CONCENTRATIONS OF DIGOXIN IN ADULT AND ELDERLY PATIENTS. Bajraktarevic, A; Kulic, M; Mehmedagic, A; Miljkovic, B; Vucicevic, K, 2016)	0.97
" In addition, we have shown that this increase is affected by dabigatran dosage and concomitant treatment with proton-pump inhibitor and digoxin."	( Effect of Bisoprolol on the Level of Dabigatran. Ivankova, J; Mokan, M; Nehaj, F; Sokol, J, )	0.33
"This study demonstrated the interaction between dabigatran and bisoprolol, which is modulated with dabigatran dosage and concomitant treatment with proton-pump inhibitor and digoxin."	( Effect of Bisoprolol on the Level of Dabigatran. Ivankova, J; Mokan, M; Nehaj, F; Sokol, J, )	0.32
"9 ng/mL after his/her initial digoxin dosage was defined as having an appropriate use of digoxin; otherwise, a patient was defined as having an inappropriate use of digoxin."	( Improvement of Adequate Digoxin Dosage: An Application of Machine Learning Approach. Hu, YH; Huang, MW; Tai, CT; Tsai, CF, 2018)	1.08
" In conclusion, these results may assist, in a mechanism-based, selection of suitable surfactants for formulating oral dosage forms to enhance the absorption of low bioavailable P-gp substrates."	( Nonionic surfactants increase digoxin absorption in Caco-2 and MDCKII MDR1 cells: Impact on P-glycoprotein inhibition, barrier function, and repeated cellular exposure. Al-Ali, AAA; Holm, R; Nielsen, CU; Steffansen, B, 2018)	0.77
" Simulation capacity provides realistic, continuous data which has the potential to substantiate alternative, less expensive, and safer digoxin-Fab dosing strategies for the treatment of acute digoxin toxicity."	( Physiologically based pharmacokinetic modelling of acute digoxin toxicity and the effect of digoxin-specific antibody fragments. Bracken, LM; Buckley, NA; Chan, BSH, 2019)	0.96
"5 mg/kg together with an infusion or oral dosing of digoxin, respectively."	( Evaluation of a Potential Clinical Significant Drug-Drug Interaction between Digoxin and Bupropion in Cynomolgus Monkeys. Chen, X; He, J; Hong, K; Jin, J; Lai, W; Li, S; Shen, Y; Xia, C; Xing, H; Xiong, A; Xu, Z; Yan, X; Yu, Y, 2018)	0.96
"The effect of multiple dosing with bupropion on the pharmacokinetics of digoxin is more pronounced."	( Evaluation of a Potential Clinical Significant Drug-Drug Interaction between Digoxin and Bupropion in Cynomolgus Monkeys. Chen, X; He, J; Hong, K; Jin, J; Lai, W; Li, S; Shen, Y; Xia, C; Xing, H; Xiong, A; Xu, Z; Yan, X; Yu, Y, 2018)	0.94
"Heart failure patients with severe renal dysfunction (GFR<60 mL/min) and/or OATP1B1 521T>C mutant-type carriers are recommended a smaller dosage of digoxin and strict therapeutic drug monitoring."	( Influence of OATP1B1 and OATP1B3 mutations and glomerular filtration rate on trough serum digoxin concentration in the Chinese population: A prospective cohort study. Chen, SQ; Cui, YM; Ding, WH; Xiang, Q; Zhang, N; Zhao, X, 2019)	0.93
" Digoxin significantly reduced HFD-induced hepatic damage, steatosis, and liver inflammation across a wide dosage range."	( Digoxin improves steatohepatitis with differential involvement of liver cell subsets in mice through inhibition of PKM2 transactivation. Arumugam, S; Chen, Y; Han, SN; Iwakiri, Y; Jiang, JX; Li, J; Liu, J; Mankash, MS; Ouyang, X; Qin, Y; Torok, NJ; Yousaf, MN; Zhao, P, 2019)	2.87
" In the absence of guidelines specifying appropriate digoxin dosing in patients undergoing continuous venovenous hemodiafiltration, anecdotal evidence-guided digoxin dosing was performed for this patient using plasma digoxin concentration-based therapeutic drug monitoring."	( Utility of Physiologically Based Pharmacokinetic Modeling in Point-of-Care Decisions: An Example Using Digoxin Dosing in Continuous Venovenous Hemodiafiltration. Chaturvedula, A; Hirani, R; Kabani, K; Palasik, B; Srinivasan, M; Tsiu, M, 2020)	1.02
" There is limited evidence to support the safety and dosage requirements of digoxin, let alone to predict its concentrations in infants."	( Predicting the serum digoxin concentrations of infants in the neonatal intensive care unit through an artificial neural network. Chen, YC; Chou, C; Lin, HW; Lin, WL; Tsai, HT; Yao, SH, 2019)	1.06
" Hence, there is small variation between therapeutic and toxic dosage of digoxin."	( Digoxin as a glycosylated steroid-like therapeutic drug: Recent advances in the clinical pharmacology and bioassays of pharmaceutical compounds. Hasanzadeh, M; Pashazadeh-Panahi, P, 2020)	2.23
" These models were then used to assess the magnitude of interaction at therapeutic venetoclax doses and to explore various clinical dosing strategies that maintain venetoclax and digoxin concentrations within their respective therapeutic windows."	( Semimechanistic Modeling to Guide Venetoclax Coadministration with Ritonavir and Digoxin. Alhadab, AA; Freise, KJ; Salem, AH, 2020)	0.98
" The final population model may be useful for the individualized dosing of digoxin for patients with cardiac insufficiency."	( Impact of SLCO4C1 Genotypes, Creatinine, and Spironolactone on Digoxin Population Pharmacokinetic Variables in Patients With Cardiac Insufficiency. Du, P; Jia, A; Li, X; Li, Y; Ma, Y; Wang, A, 2020)	1.03
" In subgroup analysis, we determined significantly greater increase in short-term mortality with use of digoxin among patients who had chronic renal disease, among patients under thrombolytic therapy and under high dosage of digoxin therapy and among female patients."	( Association of digoxin therapy with case fatality rate in acute pulmonary embolism. Çanga, Y; Emre, A; Karataş, MB; Yelgeç, NS; Zengin, A, 2021)	1.19
"A review of the evidence behind the DigiFab® dosing calculator, which provides dosing for digoxin immune Fab in patients with confirmed digoxin poisoning or overdose."	( Calculated decisions: DigiFab® (Digibind®) Dosing for Digoxin Poisoning. Lucyk, S, 2020)	1.03
" BD-15 at a dosage of 100 µg/Kg proved to be promising because it is considered therapeutic for brain disorders, since it increases the activity of the α3-Na, K-ATPase in the hippocampus and prefrontal cortex, as well as decreasing the oxidative stress in these brain regions."	( The γ-Benzylidene Digoxin Derivative BD-15 Increases the α3-Na, K-ATPase Activity in Rat Hippocampus and Prefrontal Cortex and no Change on Heart. Barbosa, LA; Cortes, VF; De Carvalho, LED; de Castro Lima, M; de Lima Santos, H; Faria, JA; Garcia, IJP; Machado, MV; Marques, SMS; Parreira, GM; Silva, IF; Villar, JAFP, 2021)	0.96
"In order to individualize the digoxin dosage regimens, this model can be used to predict digoxin serum concentration."	( Pharmacokinetics Parameters of Diagoxin among Saudi Patients in Qassim Region, Saudi Arabia. Allihimy, AS; Almadhi, J; Almeman, AA; Alnassar, NA, 2021)	0.91
"25), if concomitantly administered drugs are dosed either 2 hours before or 8 hours after the 2-hour intravenous infusion of treosulfan."	( Evaluation of the drug-drug interaction potential of treosulfan using a physiologically-based pharmacokinetic modelling approach. Balazki, P; Baumgart, J; Beelen, DW; Böhm, S; Hemmelmann, C; Hilger, RA; Martins, FS; Ring, A; Schaller, S, 2022)	0.72
" It is concluded that the glycosides oleandrin, ouabain, and digoxin in the used dosage do not present therapeutic potential for the treatment of congestive heart failure caused by doxorubicin."	( Comparative Therapeutic Potential of Cardioactive Glycosides in Doxorubicin Model of Heart Failure. Botelho, AFM; Canta, GN; da Cruz, JPO; da Silva Ferreira, R; Fernandes, PBU; Lempek, MR; Mantovani, MM; Melo, MM; Silva, FLA; Veado, JCC, 2022)	0.96
" Also, the effect of multiple dosing of parabens on p-gp expression was examined."	( Evaluation of the Effect of Isobutyl Paraben and 2-ethyl Hexyl Paraben on P-glycoprotein Functional Expression in Rats: A Pharmacokinetic Study. Alshogran, OY; Ghraiybah, NFA; I Al-Azzam, S, 2022)	0.72
" Based on the established PBPK model, following repeated dosing of 600 mg rifampicin, the deduced net effect was an approximately threefold induction in P-gp activities in the intestine, liver, and kidney."	( Robust physiologically based pharmacokinetic model of rifampicin for predicting drug-drug interactions via P-glycoprotein induction and inhibition in the intestine, liver, and kidney. Asaumi, R; Nunoya, KI; Sugiyama, Y; Taskar, KS; Yamaura, Y, 2022)	0.72
" Understanding potential drug-drug interactions (DDIs) informs proper dosing when co-administering tucatinib with other therapies."	( Evaluation of Safety and Clinically Relevant Drug-Drug Interactions with Tucatinib in Healthy Volunteers. Abdulrasool, LI; Endres, CJ; Lee, A; Mayor, JG; Rustia, EL; Sun, H; Topletz-Erickson, A; Walker, L, 2022)	0.72
" Eventually, standard dosing regimens of DABE and digoxin were assessed in Chinese old-elderly patients with chronic heart failure (CHF) with different stages of renal impairment."	( Assessment of Aging-Related Function Variations of P-gp Transporter in Old-Elderly Chinese CHF Patients Based on Modeling and Simulation. Cui, C; Jiang, Y; Li, H; Ling, J; Liu, D; Pan, J; Qu, Y; Sia, JEV; Wang, Y; Zhu, Z, 2022)	0.97
" The covariates with most influence on digoxin pharmacokinetics should be considered when adjusting this drug dosage in elder patients to achieve optimum health benefits and prevent possible side effects."	( Population pharmacokinetics of digoxin in elderly patients: A systematic review. Barcia-Hernández, E; García-Díaz, B; Salcedo-Mingoarranz, ÁL, 2022)	1.28
" This suggests that appropriate weight-based dosing with 8 to 12 µg/kg IBW has the potential to be a safer approach to digoxin loading, rather than frequently used dosing strategies that result in doses >12 µg/kg."	( Evaluation of Safety and Efficacy of Intravenous Digoxin Loading Doses Based on Ideal Body Weight. Catino, AB; Clark, JL; Dechand, JA; Jacobs, JA; Watanabe, AH, 2023)	1.37
" Future prospective studies are needed to improve and personalize GFR estimation and medication dosing in patients with cancer."	( Medication-Related Adverse Events and Discordancies in Cystatin C-Based vs Serum Creatinine-Based Estimated Glomerular Filtration Rate in Patients With Cancer. Gupta, S; Hanna, PE; Harden, D; Katz-Agranov, N; Leaf, DE; Moreno, D; Ouyang, T; Reynolds, KL; Seethapathy, H; Sise, ME; Strohbehn, IA; Wang, Q, 2023)	0.91
" The consensus identifies a straightforward approach to dosing immune antibody fragments according to the presence or absence of signs of life-threatening toxicity."	( Diagnosis and practical management of digoxin toxicity: a narrative review and consensus. Andrews, P; Anseeuw, K; Kotecha, D; Lapostolle, F; Thanacoody, R, 2023)	1.18