title: Inhibition of monocarboxylate transporter-mediated absorption of valproic acid by Gegen-Qinlian-Tang.
abstract: 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 AUC 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.
authors.affiliation: Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan 40447, R.O.C.
authors.forename: Hsueh-Jung
authors.initials: HJ
authors.lastname: Liu
authors.forename: Chung-Ping
authors.initials: CP
authors.lastname: Yu
authors.forename: Yow-Wen
authors.initials: YW
authors.lastname: Hsieh
authors.forename: Shang-Yuan
authors.initials: SY
authors.lastname: Tsai
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Hou
mesh_terms: D000042:Absorption; D000818:Animals; D000927:Anticonvulsants / Q000493:pharmacokinetics*; D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D015536:Down-Regulation / Q000187:drug effects; D004347:Drug Interactions; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014635:Valproic Acid / Q000493:pharmacokinetics*
chemical_list: D000927:Anticonvulsants; D004365:Drugs, Chinese Herbal; D014635:Valproic Acid