A Chinese herb formula decreases the monocarboxylate transporter-mediated absorption of valproic acid in rats

Huang-Qin-Tang (HQT), a Chinese medicine prescription containing Scutellariae Radix (SR), Paeoniae Radix (PR), Glycyrrhizae Radix (GR) and JuJubae Fructus (JF), was used for the treatments of cold with symptoms of abdominalgia and diarrhea. Valproic acid (VPA) is an antiepileptic drug with narrow therapeutic window. This study investigated the effect of coadministration of HQT on the pharmacokinetics of VPA, a probe drug for monocarboxylate transporter (MCT). Rats were administered VPA alone (200.0 mg/kg) and coadministered HQT (8.0 g/kg) at 0.5 h before VPA and 1.5 h after VPA in crossover designs. In addition, the chronic effect of HQT was also evaluated by coadministration of the 7th dose at 0.5 h before VPA. The serum concentration of VPA was determined by a fluorescence polarization immunoassay. The results showed that coadministration of HQT at 0.5 h before VPA significantly decreased the AUC0-t and Cmax by 62% and 77%, respectively, whereas coadministration of HQT at 1.5 h after VPA exerted no significant influence. When the 7th dose of HQT was given at 0.5 h before VPA, the AUC0-t and Cmax of VPA were markedly decreased by 65% and 82%, respectively. Mechanism study revealed that the MCT-mediated uptake of fluorescein was inhibited by HQT and each component herbs. In conclusion, the MCT-mediated absorption of VPA was significantly decreased by concomitant administration of HQT.

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