Long-Lasting Inhibition of the Intestinal Absorption of Fexofenadine by Cyclosporin a in Rats

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 (Fh) and the fraction absorbed in the intestine as an unchanged form (Fa·Fg) of FEX were increased, resulting in increased bioavailability (=Fa·Fg·Fh). At 24 h after the administration of CsA, the Fh of FEX was increased, whereas its bioavailability was decreased, suggesting that its Fa·Fg 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. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association.