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Effect of Sophora flavescens on the pharmacokinetics of carbamazepine in rats
Lei Shi,Xue-Liang Dang,Xin-You Liu,Hua-Mei Wei,Meng-Meng Yang,Yan Zhang 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.12
Carbamazepine (CBZ), an antiepilepticwith narrow therapeutic window, is a substrate ofCYP 3A4 which metabolizes CBZ to carbamazepine-10,11-epoxide (CBZE). CBZE is an active and toxicitymetabolite, and it is a substrate of MRP-2. UsingCBZ for a long time can cause hepatic injury. Sophora flavescens (SF) is a medicinal herb used forthe protected hepatic injury. This study investigatedthe acute and chronic effects of SF on the pharmacokineticsof CBZ in rats. The concentrations of CBZand CBZE in plasma and tissues were determined byHPLC method. The results showed that SF whichsignificantly decreased the AUC0-t of CBZ, increasedCBZE conversely. Tissue analysis showed that theconcentrations of CBZ and CBZE in brain and liverwere decreased by SF. In addition, the distribution ofCBZE in kidney was reduced significantly, whichinfluenced the CBZE excretion and increased the drugtoxic potentially. Results in the current study suggestthat patients using CBZ might be cautioned in the useof SF extract or Sophora-derived products. Meanwhile,patients receiving drugs which are substrates ofCYP 3A4 and/or MRP-2 should be advised of thepotential herb–drug interaction to reduce the risk oftherapeutic failure or increased toxicity of conventionaldrug therapy.