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

Drug Metabolism and Disposition

Volumn 39, Issue 11, 2011, Pages 2093-2102

  Taub, Mitchell E ^a   Mease, Kirsten ^a   Sane, Rucha S ^a   Watson, Cory A ^b   Chen, Liangfu ^b   Ellens, Harma ^b   Hirakawa, Brad ^d   Reyner, Eric L ^d   Jani, Marton ^c   Lee, Caroline A ^d  

^a BOEHRINGER INGELHEIM PHARMACEUTICALS INC   (United States)

^b GLAXOSMITHKLINE   (United States)

^c SOLVO BIOTECHNOLOGY   (Hungary)

^d PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CERIVASTATIN; DIGOXIN; KETOCONAZOLE; MONTELUKAST; ORGANIC ANION TRANSPORTER; ORGANIC ANION TRANSPORTER 1A2; ORGANIC ANION TRANSPORTER 1B1; ORGANIC ANION TRANSPORTER 1B3; ORGANIC ANION TRANSPORTER 2B1; RIFAMYCIN; SODIUM; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CONTROLLED STUDY; CULTURE MEDIUM; DRUG DISPOSITION; DRUG UPTAKE; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN EXPRESSION;

ANIMALS; BIOLOGICAL TRANSPORT; CELLS, CULTURED; CHO CELLS; CRICETINAE; DIGOXIN; DRUG INTERACTIONS; HEK293 CELLS; HUMANS; ORGANIC ANION TRANSPORTERS; ORGANIC ANION TRANSPORTERS, SODIUM-INDEPENDENT; P-GLYCOPROTEIN; RNA, MESSENGER; SODIUM; SUBSTRATE SPECIFICITY;

RATTUS;

EID: 80054734195     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.111.040816     Document Type: Article

References (36)

1. Acharya P, O'Connor MP, Polli JW, Ayrton A, Ellens H, and Bentz J (2008) Kinetic identification of membrane transporters that assist P-glycoprotein- mediated transport of digoxin and loperamide through a confluent monolayer of MDCKII-hMDR1 cells. Drug Metab Dispos 36:452-460. (Pubitemid 351185760)
2. Ahlin G, Hilgendorf C, Karlsson J, Szigyarto CA, Uhlén M, and Artursson P (2009) Endogenous gene and protein expression of drug-transporting proteins in cell lines routinely used in drug discovery programs. Drug Metab Dispos 37:2275-2283.
3. Annaba F, Sarwar Z, Kumar P, Saksena S, Turner JR, Dudeja PK, Gill RK, and Alrefai WA (2008) Modulation of ileal bile acid transporter (ASBT) activity by depletion of plasma membrane cholesterol: association with lipid rafts. Am J Physiol Gastrointest Liver Physiol 294:G489-G497. (Pubitemid 351253334)
4. Ballatori N (2005) Biology of a novel organic solute and steroid transporter, OSTalpha-OSTbeta. Exp Biol Med (Maywood) 230:689-698.
5. Ballatori N, Christian WV, Lee JY, Dawson PA, Soroka CJ, Boyer JL, Madejczyk MS, and Li N (2005) OSTalpha-OSTbeta: a major basolateral bile acid and steroid transporter in human intestinal, renal, and biliary epithelia. Hepatology 42:1270-1279. (Pubitemid 43260029)
6. Cattori V, Hagenbuch B, Hagenbuch N, Stieger B, Ha R, Winterhalter KE, and Meier PJ (2000) Identification of organic anion transporting polypeptide 4 (Oatp4) as a major full-length isoform of the liver-specific transporter-1 (rlst-1) in rat liver. FEBS Lett 474:242-245. (Pubitemid 30330842)
7. Cavet ME, West M, and Simmons NL (1996) Transport and epithelial secretion of the cardiac glycoside, digoxin, by human intestinal epithelial (Caco-2) cells. Br J Pharmacol 118:1389-1396. (Pubitemid 26248789)
8. Chu XY, Bleasby K, Yabut J, Cai X, Chan GH, Hafey MJ, Xu S, Bergman AJ, Braun MP, Dean DC, et al. (2007) Transport of the dipeptidyl peptidase-4 inhibitor sitagliptin by human organic anion transporter 3, organic anion transporting polypeptide 4C1, and multidrug resistance P-glycoprotein. J Pharmacol Exp Ther 321:673-683. (Pubitemid 46624514)
9. Cvetkovic M, Leake B, Fromm MF, Wilkinson GR, and Kim RB (1999) OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine. Drug Metab Dispos 27:866-871. (Pubitemid 29347585)
10. Dawson PA, Hubbert M, Haywood J, Craddock AL, Zerangue N, Christian WV, and Ballatori N (2005) The heteromeric organic solute transporter alpha-beta, Ostalpha-Ostbeta, is an ileal basolateral bile acid transporter. J Biol Chem 280:6960-6968. (Pubitemid 40341252)
11. de Carvalho FD and Quick M (2011) Surprising substrate versatility in SLC5A6: Na+-coupled I- transport by the human Na+/multivitamin transporter (hSMVT). J Biol Chem 286:131-137.
12. De Lannoy IA, Koren G, Klein J, Charuk J, and Silverman M (1992) Cyclosporin and quinidine inhibition of renal digoxin excretion: evidence for luminal secretion of digoxin. Am J Physiol 263:F613-F622.
13. Ding R, Tayrouz Y, Riedel KD, Burhenne J, Weiss J, Mikus G, and Haefeli WE (2004) Substantial pharmacokinetic interaction between digoxin and ritonavir in healthy volunteers. Clin Pharmacol Ther 76:73-84. (Pubitemid 38844736)
14. Dorian P, Strauss M, Cardella C, David T, East S, and Ogilvie R (1988) Digoxin-cyclosporine interaction: severe digitalis toxicity after cyclosporine treatment. Clin Invest Med 11:108-112.
15. Ernest S, Rajaraman S, Megyesi J, and Bello-Reuss EN (1997) Expression of MDR1 (multidrug resistance) gene and its protein in normal human kidney. Nephron 77:284-289. (Pubitemid 27477685)
16. Funakoshi S, Murakami T, Yumoto R, Kiribayashi Y, and Takano M (2005) Role of organic anion transporting polypeptide 2 in pharmacokinetics of digoxin and beta-methyldigoxin in rats. J Pharm Sci 94:1196-1203. (Pubitemid 40904184)
17. Gillis AM and Kates RE (1984) Clinical pharmacokinetics of the newer antiarrhythmic agents. Clin Pharmacokinet 9:375-403. (Pubitemid 14021620)
18. Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, Jessup M, Konstam MA, Mancini DM, Michl K, et al., American College of Cardiology, American Heart Association Task Force on Practice Guidelines, American College of Chest Physicians, International Society for Heart and Lung Transplantation, and Heart Rhythm Society (2005) ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society. Circulation 112:e154-235.
19. Kimoto E, Chupka J, Xiao Y, Bi Y, and Duignan D (2010) Characterization of digoxin uptake in sandwich-cultured human hepatocytes. Drug Metab Dispos 39:47-53.
20. Klein L, O'Connor CM, Gattis WA, Zampino M, de Luca L, Vitarelli A, Fedele F, and Gheorghiade M (2003) Pharmacologic therapy for patients with chronic heart failure and reduced systolic function: review of trials and practical considerations. Am J Cardiol 91:18F-40F. (Pubitemid 36555737)
21. Kullak-Ublick GA, Ismair MG, Stieger B, Landmann L, Huber R, Pizzagalli F, Fattinger K, Meier PJ, and Hagenbuch B (2001) Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology 120:525-533. (Pubitemid 32147650)
22. Lacarelle B, Rahmani R, de Sousa G, Durand A, Placidi M, and Cano JP (1991) Metabolism of digoxin, digoxigenin digitoxosides and digoxigenin in human hepatocytes and liver microsomes. Fundam Clin Pharmacol 5:567-582.
23. Lesko LJ (1989) Pharmacokinetic drug interactions with amiodarone. Clin Pharmacokinet 17:130-140.
24. Liao L, Allen LA, and Whellan DJ (2008) Economic burden of heart failure in the elderly. Pharmacoeconomics 26:447-462. (Pubitemid 351704856)
25. Lindenbaum J, Rund DG, Butler VP Jr, Tse-Eng D, and Saha JR (1981) Inactivation of digoxin by the gut flora: reversal by antibiotic therapy. N Engl J Med 305:789-794. (Pubitemid 11007233)
26. Mikkaichi T, Suzuki T, Onogawa T, Tanemoto M, Mizutamari H, Okada M, Chaki T, Masuda S, Tokui T, Eto N, et al. (2004) Isolation and characterization of a digoxin transporter and its rat homologue expressed in the kidney. Proc Natl Acad Sci USA 101:3569-3574. (Pubitemid 38338236)
27. Rameis H (1985) Quinidine-digoxin interaction: are the pharmacokinetics of both drugs altered? Int J Clin Pharmacol Ther Toxicol 23:145-153.
28. Robinson K, Johnston A, Walker S, Mulrow JP, McKenna WJ, and Holt DW (1989) The digoxin-amiodarone interaction. Cardiovasc Drugs Ther 3:25-28. (Pubitemid 19147835)
29. Saha JR, Butler VP Jr, Neu HC, and Lindenbaum J (1983) Digoxin-inactivating bacteria: identification in human gut flora. Science 220:325-327. (Pubitemid 13118491)
30. Seward DJ, Koh AS, Boyer JL, and Ballatori N (2003) Functional complementation between a novel mammalian polygenic transport complex and an evolutionarily ancient organic solute transporter, OSTalpha-OSTbeta. J Biol Chem 278:27473-27482. (Pubitemid 36899930)
31. Smith NF, Acharya MR, Desai N, Figg WD, and Sparreboom A (2005) Identification of OATP1B3 as a high-affinity hepatocellular transporter of paclitaxel. Cancer Biol Ther 4:815-818.
32. Takara K, Kakumoto M, Tanigawara Y, Funakoshi J, Sakaeda T, and Okumura K (2002) Interaction of digoxin with antihypertensive drugs via MDR1. Life Sci 70:1491-1500. (Pubitemid 34164543)
33. Tanigawara Y, Okamura N, Hirai M, Yasuhara M, Ueda K, Kioka N, Komano T, and Hori R (1992) Transport of digoxin by human P-glycoprotein expressed in a porcine kidney epithelial cell line (LLC-PK1). J Pharmacol Exp Ther 263:840-845.
34. Tuncok Y, Hazan E, Oto O, Guven H, Catalyurek H, and Kalkan S (1997) Relationship between high serum digoxin levels and toxicity. Int J Clin Pharmacol Ther 35:366-368. (Pubitemid 27417675)
35. Weiss J, Dormann SM, Martin-Facklam M, Kerpen CJ, Ketabi-Kiyanvash N, and Haefeli WE (2003) Inhibition of P-glycoprotein by newer antidepressants. J Pharmacol Exp Ther 305: 197-204. (Pubitemid 36373851)
36. Yamaguchi H, Sugie M, Okada M, Mikkaichi T, Toyohara T, Abe T, Goto J, Hishinuma T, Shimada M, and Mano N (2010) Transport of estrone 3-sulfate mediated by organic anion transporter OATP4C1: estrone 3-sulfate binds to the different recognition site for digoxin in OATP4C1. Drug Metab Pharmacokinet 25:314-317.