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The effects of Chuanxiong on the pharmacokinetics of warfarin in rats after biliary drainage

作者 Li, Haigang; Zhang, Chunhu; Fan, Rong; Sun, Hua; Xie, Haitang; Luo, Jiekun; Wang, Yang; Lv, Huiying; Tang, Tao

期刊 JOURNAL OF ETHNOPHARMACOLOGY , DEC 4 2016,:193

DOI 10.1016/j.jep.2016.08.005 PubMed 27497635

摘要 Ethnopharmacological relevance: 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.Aim of the study: 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.Materials and methods: Thirty-two rats were randomly divided into four groups: WN (healthy rats after the gastric-administration of 0.5 mg/kg warfarin sodium), WO (a rat model of biliary drainage after the gastric-administration of 0.5 mg/kg warfarin sodium), WCN (healthy rats after the gastric-administration of 0.5 mg/kg warfarin sodium and 10 g/kg Chuanxiong decoction), and WCO (a rat model of biliary drainage after the gastric-administration of 0.5 mg/kg warfarin sodium and 10 g/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.Results: 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(0-t)), peak concentration (C-max), total plasma clearance (CLz/F) and mean residence time (MRT0-t) between the WCO and WCN groups; the AUC(0-t) 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 Cmax compared the WO group (p < 0.01).Conclusion: Biliary drainage significantly influenced the disposition of warfarin, and Chuanxiong significantly affected the warfarin disposition in rat plasma. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

涉及物种 川芎 Ligusticum chuanxiong