Acute and Chronic Administrations ofRheum palmatumReduced the Bioavailability of Phenytoin in Rats: A New Herb-Drug Interaction

Author:

Chi Ying-Chang1,Juang Shin-Hun1,Chui Wai Keung2,Hou Yu-Chi34,Chao Pei-Dawn Lee3

Affiliation:

1. Institute of Pharmaceutical Chemistry, China Medical University, Taichung 40402, Taiwan

2. Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore 117543

3. School of Pharmacy, China Medical University, Taichung 40402, Taiwan

4. Department of Medical Research, China Medical University Hospital, Taichung 40402, Taiwan

Abstract

The rhizome ofRheum palmatum(RP) is a commonly used herb in clinical Chinese medicine. Phenytoin (PHT) is an antiepileptic with narrow therapeutic window. This study investigated the acute and chronic effects of RP on the pharmacokinetics of PHT in rat. Rats were orally administered with PHT (200 mg/kg) with and without RP decoction (single dose and seven doses of 2 g/kg) in a crossover design. The serum concentrations of PHT, PHT glucuronide (PHT-G), 4-hydroxyphenytoin (HPPH), and HPPH glucuronide (HPPH-G) were determined by HPLC method. Cell line models were used to identify the underlying mechanisms. The results showed that coadministration of single dose or multiple doses of RP significantly decreased theCmaxand AUC0-tas well as theK10of PHT, PHT-G, HPPH, and HPPH-G. Cell line studies revealed that RP significantly induced the P-gp-mediated efflux of PHT and inhibited the MRP-2-medicated transport of PHT and HPPH. In conclusion, acute and chronic coadministrations of RP markedly decreased the oral bioavailability of PHT via activation of P-gp, although the MRP-2-mediated excretion of PHT was inhibited. It is recommended that caution should be exercised during concurrent use of RP and PHT.

Funder

National Science Council

Publisher

Hindawi Limited

Subject

Complementary and alternative medicine

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