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

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

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.

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Conflict of interest

The authors have no conflicts of interest in relation to this paper.

Author information

Authors and Affiliations

  1. Department of Hospital Pharmacy, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan

    Yumiko Akamine & Tsukasa Uno

  2. Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan

    Yumiko Akamine & Ichiro Ieiri

  3. Department of Pharmacy, Akita University Hospital, 1-1-1 Hondo, Akita, 010-8543, Japan

    Masatomo Miura

  4. Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan

    Hisakazu Komori, Shun Saito & Ikumi Tamai

  5. Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan

    Hiroyuki Kusuhara

  6. Department of Neuropsychiatry, Hirosaki University School of Medicine, Hirosaki, Japan

    Norio Yasui-Furukori

Authors
  1. Yumiko Akamine
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  2. Masatomo Miura
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  3. Hisakazu Komori
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  4. Shun Saito
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  5. Hiroyuki Kusuhara
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  6. Ikumi Tamai
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  7. Ichiro Ieiri
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  8. Tsukasa Uno
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  9. Norio Yasui-Furukori
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Corresponding author

Correspondence to Masatomo Miura.

Additional information

Tsukasa Uno is a former member of the University of the Ryukyus.

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Akamine, Y., Miura, M., Komori, H. et al. Effects of one-time apple juice ingestion on the pharmacokinetics of fexofenadine enantiomers. Eur J Clin Pharmacol 70, 1087–1095 (2014). https://doi.org/10.1007/s00228-014-1705-y

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  • DOI: https://doi.org/10.1007/s00228-014-1705-y

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