P-glycoprotein-mediated intestinal and biliary digoxin transport in humans

Clinical Pharmacology and Therapeutics

Volumn 73, Issue 3, 2003, Pages 223-231

  Drescher, Siegfried ^a   Glaeser, Hartmut ^b   Mürdter, Thomas ^b   Hitzl, Monika ^b   Eichelbaum, Michel ^b   Fromm, Martin F ^b  

^a DR MARGARETE FISCHER BOSCH INSTITUTE OF CLINICAL PHARMACOLOGY   (Germany)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

CYTOCHROME P450 3A4; DIGOXIN; GLYCOPROTEIN P; QUINIDINE; RIFAMPICIN;

ADULT; AREA UNDER THE CURVE; ARTICLE; BILIARY EXCRETION; CATHETER; CONTROLLED STUDY; CORRELATION COEFFICIENT; DOSE RESPONSE; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG EFFECT; DRUG ELIMINATION; DRUG HALF LIFE; DRUG TRANSPORT; DRUG URINE LEVEL; HUMAN; INTESTINE CELL; INTESTINE PERFUSION; JEJUNUM; MALE; NORMAL HUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; VOLUNTEER;

ADULT; AREA UNDER CURVE; BILE; BIOLOGICAL TRANSPORT, ACTIVE; CARDIOTONIC AGENTS; CYTOCHROME P-450 ENZYME SYSTEM; DIGOXIN; DOSE-RESPONSE RELATIONSHIP, DRUG; FLUORESCENCE POLARIZATION IMMUNOASSAY; HUMANS; INFUSIONS, INTRAVENOUS; INTESTINAL ABSORPTION; JEJUNUM; MALE; P-GLYCOPROTEIN; QUINIDINE; REFERENCE VALUES; RIFAMPIN;

EID: 0037373631     PISSN: 00099236     EISSN: None     Source Type: Journal    
DOI: 10.1067/mcp.2003.27     Document Type: Article

References (26)

1. Kim RB, Fromm MF, Wandel C, Leake B, Wood AJ, Roden DM, et al. The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J Clin Invest 1998;101:289-94.
2. Watkins PB. The barrier function of CYP3A4 and P-glycoprotein in the small bowel. Adv Drug Deliv Rev 1997;27:161-70.
3. Suzuki H, Sugiyama Y. Role of metabolic enzymes and efflux transporters in the absorption of drugs from the small intestine. Eur J Pharm Sci 2000;12:3-12.
4. Zhang Y, Benet LZ. The gut as a barrier to drug absorption: combined role of cytochrome P450 3A and P-glycoprotein. Clin Pharmacokinet 2001;40:159-68.
5. Lown KS, Mayo RR, Leichtman AB, Hsiao HL, Turgeon DK, Schmiedlin-Ren P, et al. Role of intestinal P-glycoprotein (mdr1) in interpatient variation in the oral bioavailability of cyclosporine. Clin Pharmacol Ther 1997;62:248-60.
6. Gramatté T, Oertel R, Terhaag B, Kirch W. Direct demonstration of small intestinal secretion and site-dependent absorption of the beta-blocker talinolol in humans. Clin Pharmacol Ther 1996;59:541-9.
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;99:552-7.
8. Greiner B, Eichelbaum M, Fritz P, Kreichgauer HP, von Richter O, Zundler J, et al. The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin. J Clin Invest 1999;104:147-53.
9. Westphal K, Weinbrenner A, Zschiesche M, Franke G, Knoke M, Oertel R, et al. Induction of P-glycoprotein by rifampin increases intestinal secretion of talinolol in human beings: a new type of drug/drug interaction. Clin Pharmacol Ther 2000;68:345-55.
10. Dürr D, Stieger B, Kullak-Ublick GA, Rentsch KM, Steinert HC, Meier PJ, et al. St John's Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4. Clin Pharmacol Ther 2000;68:598-604.
11. Thiebaut F, Tsuruo T, Hamada H, Gottesman MM, Pastan I, Willingham MC. Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proc Natl Acad Sci U S A 1987;84:7735-8.
12. Cordon-Cardo C, O'Brien JP, Boccia J, Casals D, Bertino JR, Melamed MR. Expression of the multidrug resistance gene product (P-glycoprotein) in human normal and tumor tissues. J Histochem Cytochem 1990;38:1277-87.
13. Mayer U, Wagenaar E, Dorobek B, Beijnen JH, Borst P, Schinkel AH. Full blockade of intestinal P-glycoprotein and extensive inhibition of blood-brain barrier P-glycoprotein by oral treatment of mice with PSC833. J Clin Invest 1997;100:2430-6.
14. Mayer U, Wagenaar E, Beijnen JH, Smit JW, Meijer DK, van Asperen J, et al. Substantial excretion of digoxin via the intestinal mucosa and prevention of long-term digoxin accumulation in the brain by the mdr 1a P-glycoprotein. Br J Pharmacol 1996;119:1038-44.
15. Glaeser H, Drescher S, van der Kuip H, Behrens C, Geick A, Burk O, et al. Shed human enterocytes as a tool for the study of expression and function of intestinal drug-metabolizing enzymes and transporters. Clin Pharmacol Ther 2002;71:131-40.
16. von Richter O, Greiner B, Fromm MF, Fraser R, Omari T, Barclay ML, et al. Determination of in vivo absorption, metabolism, and transport of drugs by the human intestinal wall and liver with a novel perfusion technique. Clin Pharmacol Ther 2001;70:217-27.
17. Schinkel AH, Wagenaar E, van Deemter L, Mol CA, Borst P. Absence of the mdr1a P-Glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A. J Clin Invest 1995;96:1698-705.
18. Edelbroek M, Horowitz M, Dent J, Sun WM, Malbert C, Smout A, et al. Effects of duodenal distention on fasting and postprandial antropyloroduodenal motility in humans. Gastroenterology 1994;106:583-92.
19. Wandel C, Kim RB, Kajiji S, Guengerich P, Wilkinson GR, Wood AJ. P-glycoprotein and cytochrome P-450 3A inhibition: dissociation of inhibitory potencies. Cancer Res 1999;59:3944-8.
20. Gramatté T, Oertel R. Intestinal secretion of intravenous talinolol is inhibited by luminal R-verapamil. Clin Pharmacol Ther 1999;66:239-45.
21. Lennernäs H, Ahrenstedt O, Hallgren R, Knutson L, Ryde M, Paalzow LK. Regional jejunal perfusion, a new in vivo approach to study oral drug absorption in man. Pharm Res 1992;9:1243-51.
22. Doering W. Quinidine-digoxin interaction: Pharmacokinetics, underlying mechanism and clinical implications. N Engl J Med 1979;301:400-4.
23. Geick A, Eichelbaum M, Burk O. Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin. J Biol Chem 2001;276:14581-7.
24. Bertilsson G, Heidrich J, Svensson K, Asman M, Jendeberg L, Sydow-Backman M, et al. Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction. Proc Natl Acad Sci U S A 1998;95:12208-13.
25. Blumberg B, Sabbagh W, Jr., Juguilon H, Bolado J, Jr., van Meter CM, Ong ES, et al. SXR, a novel steroid and xenobiotic-sensing nuclear receptor. Genes Dev 1998;12:3195-205.
26. Lehmann JM, McKee DD, Watson MA, Willson TM, Moore JT, Kliewer SA. The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. J Clin Invest 1998;102:1016-23.