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Pharm Res
2002 Jun 01;196:738-43. doi: 10.1023/a:1016184211491.
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Organic anion transporter oatp2-mediated interaction between digoxin and amiodarone in the rat liver.
Kodawara T
,
Masuda S
,
Wakasugi H
,
Uwai Y
,
Futami T
,
Saito H
,
Abe T
,
Inu K
.
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PURPOSE: The interaction between amiodarone and digoxin has been known to increase serum concentrations of digoxin in humans and rats. In this study, we assessed the molecular mechanism(s) of that drug interaction, focusing on digoxin transport mediated by P-glycoprotein (Pgp) and by rat liver organic anion transporter (oatp2).
METHODS: Digoxin transport by Pgp and oatp2 was assessed using Pgp-overexpressing transfectant LLC-GA5-COL150 monolayers and oatp2-expressing Xenopus oocytes, respectively. The digoxin uptake into the isolated rat hepatocytes was also examined.
RESULTS: Amiodarone (10 microM) inhibited slightly the transcellular transport of digoxin in LLC-GA5-COL150 monolayers, whereas itraconazole (10 microM), a potent Pgp inhibitor, markedly blocked the transport. The digoxin uptake by the isolated rat hepatocytes and by the oatp2-expressing Xenopus oocytes was decreased markedly in the presence of amiodarone but not in the presence of itraconazole. In addition, amiodarone inhibited the oatp2-mediated digoxin uptake in a competitive manner with an apparent inhibition constant value of 1.8 microM.
CONCLUSION: These findings suggest that rat oatp2 rather than Pgp may be one of the interaction sites for digoxin and amiodarone in the liver.
Abe,
LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers.
2001, Pubmed,
Xenbase
Abe,
LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers.
2001,
Pubmed
,
Xenbase
Abe,
Molecular characterization and tissue distribution of a new organic anion transporter subtype (oatp3) that transports thyroid hormones and taurocholate and comparison with oatp2.
1998,
Pubmed
Bauer,
Mixed-effect modeling for detection and evaluation of drug interactions: digoxin-quinidine and digoxin-verapamil combinations.
1996,
Pubmed
Bradford,
A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.
1976,
Pubmed
Braunschweig,
Interactions of amiodarone with digoxin in rats.
1987,
Pubmed
Douste-Blazy,
Influence of amiodarone on plasma and urine digoxin concentrations.
1984,
Pubmed
Holt,
Amiodarone pharmacokinetics.
1983,
Pubmed
Iisalo,
Clinical pharmacokinetics of digoxin.
1977,
Pubmed
Inui,
Specific binding activities and cyclic GMP responses by atrial natriuretic polypeptide in kidney epithelial cell line (LLC-PK1).
1985,
Pubmed
Kullak-Ublick,
Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver.
2001,
Pubmed
,
Xenbase
Lalloz,
Binding of amiodarone by serum proteins and the effects of drugs, hormones and other interacting ligands.
1984,
Pubmed
Lambert,
Amiodarone-digoxin interaction in rats. A reduction in hepatic uptake.
1989,
Pubmed
McGovern,
Adverse reactions during treatment with amiodarone hydrochloride.
1983,
Pubmed
Miyama,
P-glycoprotein-mediated transport of itraconazole across the blood-brain barrier.
1998,
Pubmed
Moysey,
Amiodarone increases plasma digoxin concentrations.
1981,
Pubmed
Nademanee,
Amiodarone-digoxin interaction: clinical significance, time course of development, potential pharmacokinetic mechanisms and therapeutic implications.
1984,
Pubmed
Neri,
Ventricular arrhythmias in dilated cardiomyopathy: efficacy of amiodarone.
1987,
Pubmed
Noé,
Isolation of a multispecific organic anion and cardiac glycoside transporter from rat brain.
1997,
Pubmed
,
Xenbase
Oetgen,
Amiodarone-digoxin interaction. Clinical and experimental observations.
1984,
Pubmed
Robinson,
The digoxin-amiodarone interaction.
1989,
Pubmed
Seglen,
Preparation of isolated rat liver cells.
1976,
Pubmed
Tanigawara,
Transport of digoxin by human P-glycoprotein expressed in a porcine kidney epithelial cell line (LLC-PK1).
1992,
Pubmed
Vaughan Williams,
Classification of antidysrhythmic drugs.
1975,
Pubmed
Venkatesh,
Tissue-serum correlates of digoxin-amiodarone pharmacokinetic interaction in rats: evidence for selective tissue accumulation and reduced tissue binding.
1985,
Pubmed
Wakasugi,
Effect of clarithromycin on renal excretion of digoxin: interaction with P-glycoprotein.
1998,
Pubmed
Wakasugi,
[Effect of itraconazole on digoxin clearance in patients with congestive heart failure].
2000,
Pubmed
Woodland,
A model for the prediction of digoxin-drug interactions at the renal tubular cell level.
1998,
Pubmed
