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Role of organic anion transporting polypeptide 2 in pharmacokinetics of digoxin and β-methyldigoxin in rats

✍ Scribed by Sachiyo Funakoshi; Teruo Murakami; Ryoko Yumoto; Yoshie Kiribayashi; Mikihisa Takano

Publisher
John Wiley and Sons
Year
2005
Tongue
English
Weight
117 KB
Volume
94
Category
Article
ISSN
0022-3549

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✦ Synopsis

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 b-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 bmethyldigoxin 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 mg/kg. Amiodarone also significantly decreased biliary excretion and liver distribution of b-methyldigoxin, but the change in plasma levels of b-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 Oatp2mediated drug interactions.

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