Kinetic identification of membrane transporters that assist P-glycoprotein-mediated transport of digoxin and loperamide through a confluent monolayer of MDCKII-hMDR1 cells

Drug Metabolism and Disposition

Volumn 36, Issue 2, 2008, Pages 452-460

  Acharya, Poulomi ^a,b   O'Connor, Michael P ^a   Polli, Joseph W ^b   Ayrton, Andrew ^c   Ellens, Harma ^b   Bentz, Joe ^a  

^a DREXEL UNIVERSITY   (United States)

^b GLAXOSMITHKLINE   (United States)

^c GLAXOSMITHKLINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

AMPRENAVIR; BENZBROMARONE; DIGOXIN; ELACRIDAR; GLYCOPROTEIN P; LOPERAMIDE; MULTIDRUG RESISTANCE PROTEIN; ORGANIC ANION TRANSPORTER; ORGANIC CATION TRANSPORTER; QUINIDINE; URIC ACID;

ANIMAL CELL; APICAL MEMBRANE; ARTICLE; BASOLATERAL MEMBRANE; CELL LINE; CELL MEMBRANE PERMEABILITY; CONTROLLED STUDY; DRUG TRANSPORT; HUMAN; HUMAN CELL; ION TRANSPORT; KINETICS; NONHUMAN; PRIORITY JOURNAL; PROTEIN INTERACTION;

ANIMALS; CARBAMATES; CELL LINE; CELL MEMBRANE; DIGOXIN; DOGS; KINETICS; LOPERAMIDE; P-GLYCOPROTEIN; QUINIDINE; SULFONAMIDES;

EID: 38749113348     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.107.017301     Document Type: Article

References (39)

1. Acharya P, Tran TT, Polli JW, Ayrton A, Ellens H, and Bentz J (2006) P-gp expressed in a confluent monolayer of hMDR1-MDCKII cells has more than one efflux pathway with cooperative binding sites. Biochemistry 45:15505-15519.
2. Bartholomé K, Rius M, Letschert K, Keller D, Timmer J, and Keppler D (2007) Data-based mathematical modeling of vectorial transport across double-transfected polarized cells. Drug Metab Dispos 35:1476-1481.
3. Bentz J, Tran TT, Polli JW, Ayrton A, and Ellens H (2005) The steady-state Michaelis-Menten analysis of P-glycoprotein mediated transport through a confluent cell monolayer cannot predict the correct Michaelis constant Km. Pharmacol Res 22:1667-1677.
4. Collett A, Tanianis-Hughes J, Carlson GL, Harwood MD, and Warhurst G (2005) 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 26:386-393.
5. Dean M, Rzhetsky A, and Allikmets R (2001) The human ATP-binding cassette (ABC) transporter superfamily. Genome Res 11:1156-1166.
6. Dresser MJ, Leabman MK, and Giacomini KM (2001) Transporters involved in the elimination of drugs in the kidney: organic anion transporters and organic cation transporters. J Pharm Sci 90:397-421.
7. Enomoto A and Endou H (2005) Roles of organic anion transporters (OATs) and a urate transporter (URAT1) in the pathophysiology of human disease. Clin Exp Nephrol 9:195-205.
8. Harris MJ, Kagawa T, Dawson PA, and Arias IM (2004) Taurocholate transport by hepatic and intestinal bile acid transporters is independent of FIC1 overexpression in Madin-Darby canine kidney cells. J Gastroenterol Hepatol 19:819-825.
9. Horikawa M, Kato Y, Tyson CA, and Sugiyama Y (2002) The potential for an interaction between MRP2 (ABCC2) and various therapeutic agents: probenecid as a candidate inhibitor of the biliary excretion of irinotecan metabolites. Drug Metab Pharmacokinet 17:23-33.
10. Hyafil F, Vergely C, Du Vignaud P, and Grand-Perret T (1993) In vitro and in vivo reversal of multidrug resistance by GF120918, an acridone carboxamide derivative. Cancer Res 53:4595-4602.
11. Ismair MG, Stanca C, Ha HR, Renner EL, Meier PJ, and Kullak-Ublick GA (2003) Interactions of glycyrrhizin with organic anion transporting polypeptides of rat and human liver. Hepatol Res 26:343-347.
12. Iwanaga T, Kobayashi D, Hirayama M, Maeda T, and Tamai I (2005) Involvement of uric acid transporter in increased renal clearance of the xanthine oxidase inhibitor oxypurinol induced by a uricosuric agent, benzbromarone. Drug Metab Dispos 33:1791-1795.
13. Juliano RL and Ling V (1976) A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta 455:152-162.
14. Kikuchi R, Kusuhara H, Abe T, Endou H, and Sugiyama Y (2004) Involvement of multiple transporters in the efflux of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors across the blood-brain barrier. J Pharmacol Exp Ther 311:1147-1153.
15. m value of efflux pump substrates. Drug Metab Dispos 35:1574-1579.
16. Lau YY, Okochi H, Huang Y, and Benet LZ (2006) Multiple transporters affect the disposition of atorvastatin and its two active hydroxy metabolites: application of in vitro and ex situ systems. J Pharmacol Exp Ther 316:762-771.
17. Loo TW and Clarke DM (2005) Recent progress in understanding the mechanism of Pglycoprotein-mediated drug efflux. J Membr Biol 206:173-185.
18. Lugo MR and Sharom FJ (2005) Interaction of LDS-751 with P-glycoprotein and mapping of the location of the R drug binding site. Biochemistry 44:643-655.
19. +/taurocholate cotransporting polypeptide (SLC10A1) and bile salt export pump (ABCB 11)-coexpressing LLC-PK1 cells by cholestasis-inducing drugs. Drug Metab Dispos 34:1575-1581.
20. Mizuno N, Niwa T, Yotsumoto Y, and Sugiyama Y (2003) Impact of drug transporter studies on drug discovery and development. Pharmacol Rev 55:425-461.
21. Morita N, Kusuhara H, Sekine T, Endou H, and Sugiyama Y (2001) Functional characterization of rat organic anion transporter 2 in LLC-PK1 Cells. J Pharmacol Exp Ther 298:1179-1184.
22. Morrow CS, Peklak-Scott C, Bishwokarma B, Kute TE, Smitherman PK, and Townsend AJ (2006) Multidrug resistance protein 1 (MRP1, ABCC1) mediates resistance to mitoxantrone via glutathione-dependent drug efflux. Mol Pharmacol 69:1499-1505.
23. Pan G and Elmquist WF (2007) Mitoxantrone permeability in MDCKII cells is influenced by active influx transport. Mol Pharmacol 4:475-483.
24. Petri N, Tannergren C, Rungstad D, and Lennernas H (2004) Transport characteristics of fexofenadine in the Caco-2 cell model. Pharmacol Res 21:1398-1404.
25. Press WH, Teukolsky SA, Vettering WT, and Flannery BP (1992) Numerical Recipes in C: The Art of Scientific Computing, 2nd ed, Cambridge University Press, Cambridge, UK.
26. Quinn GP and Keough MJ (2002) Experimental Design and Data Analysis for Biologists, Cambridge University Press, Cambridge, UK.
27. Rao PV (1998) Statistical Research Methods in the Life Sciences, Duxbury Press, Pacific Grove, CA.
28. Rautio J, Humphreys JE, Webster LO, Balakrishnan A, Keogh JP, Kunta JR, Serabjit-Singh CJ, and Polli JW (2006) In vitro P-glycoprotein inhibition assays for assessment of clinical drug interaction potential of new drug candidates: a recommendation for probe substrates. Drug Metab Dispos 34:786-792.
29. Robertson EE and Rankin GO (2006) Human renal organic anion transporters: characteristics and contributions to drug and drug metabolite excretion. Pharmacol Ther 109:399-412.
30. Sekine T, Miyazaki H, and Endou H (2006) Molecular physiology of renal organic anion transporters. Am J Physiol Renal Physiol 290:F251-F261.
31. Shitara Y, Horiea T, and Sugiyama Y (2006) Transporters as a determinant of drug clearance and tissue distribution. Eur J Pharm Sci 27:425-446.
32. Sokal RR and Rohlf FJ (1995) Biometry, 3rd ed, W. H. Freeman and Company, New York.
33. Spears KJ, Ross J, Stenhouse A, Ward CJ, Goh LB, Wolf CR, Morgan P, Ayrton A, and Friedberg TH (2005) Directional trans-epithelial transport of organic anions in porcine LLC-PK1 cells that co-express human OATP1B1 (OATP-C) and MRP2. Biochem Pharmacol 69:415-423.
34. Sugiyama D, Kusuhara H, Shitara Y, Abe T, Meier PJ, and Sekine T (2001) Characterization of the efflux transport of 17β-estradiold-17β- glucuronide from the brain across the blood-brain barrier. J Pharmacol Exp Ther 298:316-322.
35. Tahara H, Kusuhara H, Maeda K, Koepsell H, Fuse E, and Sugiyama Y (2006) Inhibition of Oat3-mediated renal uptake as a mechanism for drug-drug interaction between fexofenadine and probenecid. Drug Metab Dispos 34:743-747.
36. Tang F, Horie K, and Borchardt RT (2002) Are MDCK cells transfected with the human MDR1 gene a good model of the human intestinal mucosa? Pharmacol Res 19:773-779.
37. Tran TT, Mittal A, Aldinger T, Polli JW, Ayrton A, Ellens H, and Bentz J (2005) The elementary mass action rate constants of P-gp transport for a confluent monolayer of MDCKII-hMDR1 cells. Biophys J 88:715-738.
38. Troutman MD and Thakker DR (2003) novel experimental parameters to quantify the modulation of absorptive and secretory transport of substrates by P-glycoprotein in cell culture models of intestinal epithelium. Pharmacol Res 220:1210-1224.
39. Vavricka SR, Montfoort JV, Ha HR, Meier PJ, and Fattinger K (2002) Interactions of rifamycin SV and rifampicin with organic anion uptake systems of human liver. Hepatology 36:164-172.