Effects of one-time apple juice ingestion on the pharmacokinetics of fexofenadine enantiomers

Yumiko Akamine, Masatomo Miura, Hisakazu Komori, Shun Saito, Hiroyuki Kusuhara, Ikumi Tamai, Ichiro Ieiri, Tsukasa Uno, Norio Yasui-Furukori

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)


Purpose: We examined the effect of a single apple juice intake on the pharmacokinetics of fexofenadine enantiomers in healthy Japanese subjects. Methods: In a randomized two phase, open-label crossover study, 14 subjects received 60 mg of racemic fexofenadine simultaneously with water or apple juice. For the uptake studies, oocytes expressing organic anion-transporting polypeptide 2B1 (OATP2B1) were incubated with 100 μM (R)- and (S)-fexofenadine in the presence or absence of 10 % apple juice. Results: One-time ingestion of apple juice significantly decreased the area under the plasma concentration-time curve (AUC0-24) for (R)- and (S)-fexofenadine by 49 and 59 %, respectively, and prolonged the time to reach the maximum plasma concentration (t max) of both enantiomers (P∈<∈0.001). Although apple juice greatly reduced the amount of (R)- and (S)-fexofenadine 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 (cRNA)-injected oocytes was significantly higher than that into water-injected oocytes, and this effect was greater for (R)-fexofenadine. In addition, apple juice significantly decreased the uptake of both enantiomers into OATP2B1 cRNA-injected oocytes. Conclusions: These results suggest that OATP2B1 plays an important role in the stereoselective pharmacokinetics of fexofenadine and that one-time apple juice ingestion probably inhibits intestinal OATP2B1-mediated 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.

Original languageEnglish
Pages (from-to)1087-1095
Number of pages9
JournalEuropean Journal of Clinical Pharmacology
Issue number9
Publication statusPublished - Sept 2014

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)


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