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Drug Metab Pharmacokinet. 2015 Oct;30(5):352-7. doi: 10.1016/j.dmpk.2015.06.005. Epub 2015 Jun 26.

The change of pharmacokinetics of fexofenadine enantiomers through the single and simultaneous grapefruit juice ingestion.

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Department of Pharmacy, Akita University Hospital, Akita, Japan.
Department of Pharmacy, Akita University Hospital, Akita, Japan. Electronic address:
Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.
Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Department of Neuropsychiatry, Hirosaki University School of Medicine, Hirosaki, Japan.
Department of Pharmacy, Zikeikai-Aoimori Hospital, Aomori, Japan.


The stereoselective pharmacokinetics of fexofenadine are associated with OATP2B1-mediated transport, and grapefruit juice (GFJ) is an inhibitor of OATP2B1. Therefore, in this study, we aimed to investigate whether and to what extent GFJ ingestion affected the pharmacokinetics of fexofenadine enantiomers in healthy subjects. In a randomized, two-phase, open-label, crossover study, 14 subjects received 60 mg of racemic fexofenadine simultaneously with water or GFJ. Ingestion of GFJ significantly decreased the areas under the plasma concentration-time curve (AUC0-24) for (R)- and (S)-fexofenadine by 39% and 52%, respectively. Subsequently, GFJ increased the mean R/S ratio of the AUC0-24 from 1.58 to 1.96 (P < 0.05). Although GFJ greatly reduced the amounts of (R)- and (S)-fexofenadine excreted into the urine (Ae0-24) by 52% and 61%, respectively, the mean R/S ratios of Ae0-24 and the renal clearances of both enantiomers were unchanged between the control and GFJ phases. GFJ, an OATP2B1 inhibitor, significantly reduced the plasma concentrations of fexofenadine enantiomers, exhibiting clinically moderate effects. The present results suggested that changes in OATP2B1 activity by GFJ may alter the stereoselective pharmacokinetics of fexofenadine and that reduced intestinal OATP2B1 activity may affect the stereoselectivity of fexofenadine.


Enantiomer; Fexofenadine; Grapefruit juice; OATP2B1; Pharmacokinetics

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