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Valproic acid (VPA), an anti-epileptic drug with a narrow therapeutic index, is a substrate of the monocarboxylate transporter (MCT). In this study, we investigated the effect of Gegen-Qinlian-Tang (GQT), a Chinese Medicine prescription containing Puerariae Radix (PR), Scutellariae Radix (SR), Coptidis Rhizoma (CR) and Glycyrrhizae Radix (GR), on the pharmacokinetics of VPA, as a probe drug of MCT, in rats and the underlying mechanism. Sprague-Dawley rats were orally administered VPA with and without GQT in crossover design. The serum concentrations of VPA were determined by a fluorescence polarization immunoassay. The results showed that coadministration with 2.0 and 4.0 g/kg of GQT remarkably decreased the Cmax of VPA by 72% and 74% and reduced the 0-t by 63% and 53%, respectively. The mechanism study using Caco-2 cells revealed that the uptake function of MCT was inhibited by GQT and each component herb. In conclusion, the MCT-mediated absorption of VPA was significantly decreased by GQT and its component herbs. [ABSTRACT FROM AUTHOR]