Effects of one-time apple juice ingestion on the pharmacokinetics of fexofenadine enantiomers
| Autor: | Masatomo Miura, Hiroyuki Kusuhara, Ikumi Tamai, Ichiro Ieiri, Yumiko Akamine, Norio Yasui-Furukori, Shun Saito, Hisakazu Komori, Tsukasa Uno |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Histamine H1 Antagonists Non-Sedating Malus Pharmacology toxicology Organic Anion Transporters Pharmacology Intestinal absorption RNA Complementary Beverages Eating Food-Drug Interactions Xenopus laevis Young Adult Pharmacokinetics Anti-Allergic Agents medicine Animals Humans Ingestion Pharmacology (medical) Cross-Over Studies Fexofenadine biology Chemistry fungi Stereoisomerism General Medicine equipment and supplies biology.organism_classification Crossover study Intestinal Absorption Area Under Curve Fruit Oocytes bacteria Female Terfenadine Enantiomer medicine.drug |
| Zdroj: | European Journal of Clinical Pharmacology. 70:1087-1095 |
| ISSN: | 1432-1041 0031-6970 |
| Popis: | We examined the effect of a single apple juice intake on the pharmacokinetics of fexofenadine enantiomers in healthy Japanese subjects.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.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.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. |
| Databáze: | OpenAIRE |
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