Modeling the kinetics of digoxin absorption: Enhancement by P-glycoprotein inhibition

Journal of Clinical Pharmacology

Volumn 52, Issue 3, 2012, Pages 381-387

  Weiss, Michael ^a,b   Sermsappasuk, Pakawadee ^a   Siegmund, Werner ^c  

^a NARESUAN UNIVERSITY   (Thailand)

^b MARTIN LUTHER UNIVERSITY HALLE WITTENBERG   (Germany)

^c UNIVERSITY OF GREIFSWALD   (Germany)

Author keywords

absorption rate; bioavailability; digoxin; P glycoprotein inhibition; population pharmacokinetics

Indexed keywords

DIGOXIN; GLYCOPROTEIN P; TALINOLOL;

AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DISTRIBUTION VOLUME; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG POTENTIATION; HUMAN; HUMAN EXPERIMENT; NORMAL DISTRIBUTION; NORMAL HUMAN; SINGLE DRUG DOSE; TIME TO MAXIMUM PLASMA CONCENTRATION;

ABSORPTION; ANTI-ARRHYTHMIA AGENTS; AREA UNDER CURVE; BIOLOGICAL AVAILABILITY; CARDIOTONIC AGENTS; COMPUTER SIMULATION; DIGOXIN; DRUG INTERACTIONS; HUMANS; MODELS, BIOLOGICAL; NORMAL DISTRIBUTION; P-GLYCOPROTEIN; PROPANOLAMINES;

EID: 84860005744     PISSN: 00912700     EISSN: 15524604     Source Type: Journal    
DOI: 10.1177/0091270010396711     Document Type: Article

References (28)

1. Ahmed A, Pitt B, Rahimtoola SH, et al. Effects of digoxin at low serum concentrations on mortality and hospitalization in heart failure: a propensity-matched study of the DIG trial. Int J Cardiol. 2008 ; 123 (2). 138-146
2. Greiner B, Eichelbaum M, Fritz P, et al. The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin. J Clin Invest. 1999 ; 104 (2). 147-153
3. Santostasi G, Fantin M, Maragno I, Gaion RM, Basadonna O, Dalla-Volta S. Effects of amiodarone on oral and intravenous digoxin kinetics in healthy subjects. J Cardiovasc Pharmacol. 1987 ; 9 (4). 385-390
4. Rodin SM, Johnson BF, Wilson J, Ritchie P, Johnson J. Comparative effects of verapamil and isradipine on steady-state digoxin kinetics. Clin Pharmacol Ther.. 1988 ; 43 (6). 668-672
5. De Mey C, Brendel E, Enterling D. Carvedilol increases the systemic bioavailability of oral digoxin. Br J Clin Pharmacol. 1990 ; 29 (4). 486-490
6. Pedersen KE, Christiansen BD, Klitgaard NA, Nielsen-Kudsk F. Effect of quinidine on digoxin bioavailability. Eur J Clin Pharmacol. 1983 ; 24 (1). 41-47
7. Fromm MF, Kim RB, Stein CM, Wilkinson GR, Roden DM. Inhibition of P-glycoprotein-mediated drug transport: a unifying mechanism to explain the interaction between digoxin and quinidine. Circulation. 1999 ; 99 (4). 552-557
8. Kovarik JM, Rigaudy L, Guerret M, Gerbeau C, Rost KL. Longitudinal assessment of a P-glycoprotein-mediated drug interaction of valspodar on digoxin. Clin Pharmacol Ther. 1999 ; 66 (4). 391-400
9. Westphal K, Weinbrenner A, Giessmann T, et al. Oral bioavailability of digoxin is enhanced by talinolol: evidence for involvement of intestinal P-glycoprotein. Clin Pharmacol Ther. 2000 ; 68 (1). 6-12
10. Boyd RA, Stern RH, Stewart BH, et al. Atorvastatin coadministration may increase digoxin concentrations by inhibition of intestinal P-glycoprotein- mediated secretion. J Clin Pharmacol. 2000 ; 40 (1). 91-98
11. Angirasa AK, Koch AZ. P-glycoprotein as the mediator of itraconazole-digoxin interaction. J Am Podiatr Med Assoc.. 2002 ; 92 (8). 471-472
12. Verstuyft C, Strabach S, El-Morabet H, et al. Dipyridamole enhances digoxin bioavailability via P-glycoprotein inhibition. Clin Pharmacol Ther.. 2003 ; 73 (1). 51-60
13. Tayrouz Y, Ding R, Burhenne J, et al. Pharmacokinetic and pharmaceutic interaction between digoxin and Cremophor RH40. Clin Pharmacol Ther.. 2003 ; 73 (5). 397-405
14. Ding R, Tayrouz Y, Riedel KD, et al. Substantial pharmacokinetic interaction between digoxin and ritonavir in healthy volunteers. Clin Pharmacol Ther.. 2004 ; 76 (1). 73-84
15. Weiss M. A novel extravascular input function for the assessment of drug absorption in bioavailability studies. Pharm Res.. 1996 ; 13 (10). 1547-1553
16. Wang J, Weiss M, D'Argenio DZ. A note on population analysis of dissolution-absorption models using the inverse Gaussian function. J Clin Pharmacol. 2008 ; 48 (6). 719-725
17. Kramer WG, Lewis RP, Cobb TC, et al. Pharmacokinetics of digoxin: comparison of a two- and a three-compartment model in man. J Pharmacokinet Biopharm. 1974 ; 2 (4). 299-312
18. D'Argenio DZ, Schumitzky A, Wang X ADAPT 5 User's Guide: Pharmacokinetic /Pharmacodynamic Systems Analysis Software. Los Angeles, CA: Biomedical Simulations Resource ; 2009 :
19. Rengelshausen J, Goggelmann C, Burhenne J, et al. Contribution of increased oral bioavailability and reduced nonglomerular renal clearance of digoxin to the digoxin-clarithromycin interaction. Br J Clin Pharmacol. 2003 ; 56 (1). 32-38
20. Hinderling PH, Hartmann D. Pharmacokinetics of digoxin and main metabolites/derivatives in healthy humans. Ther Drug Monit. 1991 ; 13 (5). 381-401
21. Kurata Y, Ieiri I, Kimura M, et al. Role of human MDR1 gene polymorphism in bioavailability and interaction of digoxin, a substrate of P-glycoprotein. Clin Pharmacol Ther. 2002 ; 72 (2). 209-219
22. Cohen AF, Kroon R, Schoemaker HC, Breimer DD, Van Vliet-Verbeek A, Brandenburg HC. The bioavailability of digoxin from three oral formulations measured by a specific h.p.l.c. assay. Br J Clin Pharmacol. 1993 ; 35 (2). 136-142
23. Salphati L, Benet LZ. Effects of ketoconazole on digoxin absorption and disposition in rat. Pharmacology. 1998 ; 56 (6). 308-313
24. Sababi M, Borga O, Hultkvist-Bengtsson U. The role of P-glycoprotein in limiting intestinal regional absorption of digoxin in rats. Eur J Pharm Sci.. 2001 ; 14 (1). 21-27
25. Englund G, Hallberg P, Artursson P, Michaelsson K, Melhus H. Association between the number of coadministered P-glycoprotein inhibitors and serum digoxin levels in patients on therapeutic drug monitoring. BMC Med.. 2004 ; 2: 8
26. Fenner KS, Troutman MD, Kempshall S, et al. Drug-drug interactions mediated through P-glycoprotein: clinical relevance and in vitro-in vivo correlation using digoxin as a probe drug. Clin Pharmacol Ther.. 2009 ; 85 (2). 173-181
27. Weiss M, Kang W. Inotropic effect of digoxin in humans: mechanistic pharmacokinetic/pharmacodynamic model based on slow receptor binding. Pharm Res.. 2004 ; 21 (2). 231-236
28. Collett A, Tanianis-Hughes J, Carlson GL, et al. Comparison of P-glycoprotein-mediated drug-digoxin interactions in Caco-2 with human and rodent intestine: relevance to in vivo prediction. Eur J Pharm Sci.. 2005 ; 5: 386-393