Long-lasting inhibition of the intestinal absorption of fexofenadine by cyclosporin A in rats.

Kei Suzuki, Yoshihisa Shitara, Kousuke Fukuda, Toshiharu Horie

Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.

Journal of pharmaceutical sciences 2012 Jul

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The purpose of the present study is to examine the long-lasting inhibition of intestinal organic anion transporting polypeptides (Oatps) by cyclosporin A (CsA) in rats using fexofenadine (FEX) as a probe drug. We examined the pharmacokinetics of FEX after its intravenous or oral administration to rats at 3 or 24 h after the oral administration of CsA. When FEX was administered at 3 h after the administration of CsA, its plasma concentration increased regardless of whether it was administered intravenously or orally. When FEX was intravenously administered at 24 h after the oral administration of CsA, its plasma concentration was increased; however, that observed after its oral administration was not significantly different from the vehicle-treated control. When FEX was administered at 3 h after the administration of CsA, the hepatic availability (F(h)) and the fraction absorbed in the intestine as an unchanged form (F(a)·F(g)) of FEX were increased, resulting in increased bioavailability (=F(a)·F(g)·F(h)). At 24 h after the administration of CsA, the F(h) of FEX was increased, whereas its bioavailability was decreased, suggesting that its F(a)·F(g) was decreased because of the long-lasting inhibition. In conclusion, CsA has long-lasting inhibitory effects on Oatps in the rat intestine as well as in the liver. Copyright © 2012 Wiley Periodicals, Inc.

Citation

Kei Suzuki, Yoshihisa Shitara, Kousuke Fukuda, Toshiharu Horie. Long-lasting inhibition of the intestinal absorption of fexofenadine by cyclosporin A in rats. Journal of pharmaceutical sciences. 2012 Jul;101(7):2606-15