title: Effect of Sophora flavescens on the pharmacokinetics of carbamazepine in rats.
abstract: Carbamazepine (CBZ), an antiepileptic with narrow therapeutic window, is a substrate of CYP 3A4 which metabolizes CBZ to carbamazepine-10,11-epoxide (CBZE). CBZE is an active and toxicity metabolite, and it is a substrate of MRP-2. Using CBZ for a long time can cause hepatic injury. Sophora flavescens (SF) is a medicinal herb used for the protected hepatic injury. This study investigated the acute and chronic effects of SF on the pharmacokinetics of CBZ in rats. The concentrations of CBZ and CBZE in plasma and tissues were determined by HPLC method. The results showed that SF which significantly decreased the AUC0-t of CBZ, increased CBZE conversely. Tissue analysis showed that the concentrations of CBZ and CBZE in brain and liver were decreased by SF. In addition, the distribution of CBZE in kidney was reduced significantly, which influenced the CBZE excretion and increased the drug toxic potentially. Results in the current study suggest that patients using CBZ might be cautioned in the use of SF extract or Sophora-derived products. Meanwhile, patients receiving drugs which are substrates of CYP 3A4 and/or MRP-2 should be advised of the potential herb-drug interaction to reduce the risk of therapeutic failure or increased toxicity of conventional drug therapy.
authors.affiliation: Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, People's Republic of China, shilei1860@hotmail.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Xue-Liang
authors.initials: XL
authors.lastname: Dang
authors.forename: Xin-You
authors.initials: XY
authors.lastname: Liu
authors.forename: Hua-Mei
authors.initials: HM
authors.lastname: Wei
authors.forename: Meng-Meng
authors.initials: MM
authors.lastname: Yang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D019540:Area Under Curve; D002220:Carbamazepine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D029909:Sophora / Q000737:chemistry*; D013379:Substrate Specificity; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D018528:ATP-Binding Cassette Transporters; C423013:Abcc2 protein, rat; D010936:Plant Extracts; D002220:Carbamazepine; C465260:Cyp3a2 protein, rat; D051544:Cytochrome P-450 CYP3A; C012227:carbamazepine epoxide