Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8994649 | Journal of Pharmaceutical Sciences | 2005 | 8 Pages |
Abstract
Recently, we found that potent P-glycoprotein (P-gp) inhibitors, such as verapamil and cyclosporin A, markedly modulated the pharmacokinetics of digoxin in rats, whereas they did not affect β-methyldigoxin pharmacokinetics significantly. Digoxin is also a substrate of rat organic anion transporting polypeptide 2 (Oatp2). Here, we compared the magnitude of Oatp2-mediated drug interaction of digoxin and β-methyldigoxin using amiodarone as an Oatp2 inhibitor in rats. Amiodarone (20 mg/kg) given intravenously significantly increased plasma levels and decreased biliary excretion, liver distribution, and intestinal distribution of digoxin administered intravenously at a dose of 10 μg/kg. Amiodarone also significantly decreased biliary excretion and liver distribution of β-methyldigoxin, but the change in plasma levels of β-methyldigoxin was quite small. These findings may give a clue in selecting these cardiac glycosides in clinical pharmacotherapy for patients receiving multiple drugs towards escape from Oatp2-mediated drug interactions. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association
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Authors
Sachiyo Funakoshi, Teruo Murakami, Ryoko Yumoto, Yoshie Kiribayashi, Mikihisa Takano,