Authors: Yumiko Akamine Masatomo Miura Hisakazu Komori Shun Saito Hiroyuki Kusuhara Ikumi Tamai Ichiro Ieiri Tsukasa Uno Norio YasuiFurukori
Publish Date: 2014/06/07
Volume: 70, Issue: 9, Pages: 1087-1095
Abstract
In a randomized two phase openlabel crossover study 14 subjects received 60 mg of racemic fexofenadine simultaneously with water or apple juice For the uptake studies oocytes expressing organic aniontransporting polypeptide 2B1 OATP2B1 were incubated with 100 μM R and Sfexofenadine in the presence or absence of 10 apple juiceOnetime ingestion of apple juice significantly decreased the area under the plasma concentration–time curve AUC0–24 for R and Sfexofenadine by 49 and 59 respectively and prolonged the time to reach the maximum plasma concentration t max of both enantiomers P 0001 Although apple juice greatly reduced the amount of R and Sfexofenadine excretion into urine Ae0–24 by 54 and 58 respectively the renal clearances of both enantiomers were unchanged between the control and apple juice phases For in vitro uptake studies the uptake of both fexofenadine enantiomers into OATP2B1 complementary RNA cRNAinjected oocytes was significantly higher than that into waterinjected oocytes and this effect was greater for Rfexofenadine In addition apple juice significantly decreased the uptake of both enantiomers into OATP2B1 cRNAinjected oocytesThese results suggest that OATP2B1 plays an important role in the stereoselective pharmacokinetics of fexofenadine and that onetime apple juice ingestion probably inhibits intestinal OATP2B1mediated transport of both enantiomers In addition this study demonstrates that the OATP2B1 inhibition effect does not require repeated ingestion or a large volume of apple juice
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