Department of Integrated Traditional Chinese and Western Medicine, Laboratory of Ethnopharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China; Department of Pharmacy, Changsha Medical University, Changsha 410219, PR China.
Department of Integrated Traditional Chinese and Western Medicine, Laboratory of Ethnopharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China.
J Ethnopharmacol. 2016 Dec 4;193:117-124. doi: 10.1016/j.jep.2016.08.005. Epub 2016 Aug 3.
Chuanxiong Rhizoma (rhizomes of Ligusticum chuanxiong Hort), known as Chuanxiong in Chinese, has been used for treating cardiovascular diseases for centuries. Chuanxiong is a classical activating blood circulation herb in the treatment of thromboembolism heart diseases. Warfarin often combines with herbal prescriptions containing Chuanxiong in China.
The herb-drug interaction involving enterohepatic circulation process remains unclear. This study aimed to elucidate the effects of Chuanxiong Rhizoma on the pharmacokinetics of warfarin in rats after biliary drainage.
Thirty-two rats were randomly divided into four groups: WN (healthy rats after the gastric-administration of 0.5mg/kg warfarin sodium), WO (a rat model of biliary drainage after the gastric-administration of 0.5mg/kg warfarin sodium), WCN (healthy rats after the gastric-administration of 0.5mg/kg warfarin sodium and 10g/kg Chuanxiong decoction), and WCO (a rat model of biliary drainage after the gastric-administration of 0.5mg/kg warfarin sodium and 10g/kg Chuanxiong decoction). The levels of warfarin and internal standard were quantified by LC-MS/MS. Comparisons between groups were performed according to the main pharmacokinetic parameters calculated by the DAS 2.1.1 software.
The established LC-MS/MS method was specific, precise and rapid. The pharmacokinetic parameters showed a significant difference between the WN and WO groups. There were significant differences in the area under the curve (AUC), peak concentration (C), total plasma clearance (CLz/F) and mean residence time (MRT) between the WCO and WCN groups; the AUC of warfarin in the WCN group was 2.42 times than that of the WN group (p<0.01); the WCO group displayed a decreased to 61.6% in the C compared the WO group (p<0.01).
Biliary drainage significantly influenced the disposition of warfarin, and Chuanxiong significantly affected the warfarin disposition in rat plasma.
川芎（川芎的根茎），在中国被称为川芎，几个世纪以来一直被用于治疗心血管疾病。川芎是治疗血栓栓塞性心脏病的经典活血药。华法林在中国常与含有川芎的草药方剂联合使用。
涉及肠肝循环过程的草药-药物相互作用尚不清楚。本研究旨在阐明胆道引流后川芎对大鼠华法林药代动力学的影响。
32 只大鼠随机分为四组：WN（健康大鼠，胃内给予 0.5mg/kg 华法林钠后）、WO（胃内给予 0.5mg/kg 华法林钠后胆道引流大鼠模型）、WCN（健康大鼠，胃内给予 0.5mg/kg 华法林钠和 10g/kg 川芎汤后）和 WCO（胃内给予 0.5mg/kg 华法林钠和 10g/kg 川芎汤后胆道引流大鼠模型）。采用 LC-MS/MS 定量检测华法林和内标物的水平。根据 DAS 2.1.1 软件计算的主要药代动力学参数对各组进行比较。
建立的 LC-MS/MS 方法特异性强、精密度高、快速。WN 组和 WO 组的药代动力学参数有显著差异。WCO 组和 WCN 组间 AUC、C、总血浆清除率（CLz/F）和平均驻留时间（MRT）有显著差异；WCN 组华法林 AUC 是 WN 组的 2.42 倍（p<0.01）；WCO 组 C 较 WO 组降低 61.6%（p<0.01）。
胆道引流显著影响华法林的处置，川芎显著影响大鼠血浆中华法林的处置。
