title: The effects of Chuanxiong on the pharmacokinetics of warfarin in rats after biliary drainage.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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 (AUC0-t), peak concentration (Cmax), total plasma clearance (CLz/F) and mean residence time (MRT0-t) between the WCO and WCN groups; the AUC0-tof 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 Cmaxcompared the WO group (p<0.01).
  
  
  CONCLUSIONS
  Biliary drainage significantly influenced the disposition of warfarin, and Chuanxiong significantly affected the warfarin disposition in rat plasma.
authors: 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.
authors: Haigang
authors: H
authors: Li
authors: Department of Integrated Traditional Chinese and Western Medicine, Laboratory of Ethnopharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China.
authors: Chunhu
authors: C
authors: Zhang
authors: Department of Integrated Traditional Chinese and Western Medicine, Laboratory of Ethnopharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China.
authors: Rong
authors: R
authors: Fan
authors: Anhui Provincial Centre for Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu 241001, PR China.
authors: Hua
authors: H
authors: Sun
authors: Anhui Provincial Centre for Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu 241001, PR China.
authors: Haitang
authors: H
authors: Xie
authors: Department of Integrated Traditional Chinese and Western Medicine, Laboratory of Ethnopharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China.
authors: Jiekun
authors: J
authors: Luo
authors: Department of Integrated Traditional Chinese and Western Medicine, Laboratory of Ethnopharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China. Electronic address: wangyang_xy87@163.com.
authors: Yang
authors: Y
authors: Wang
authors: Hunan Agricultural Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha 410125, PR China. Electronic address: 117324662@qq.com.
authors: Huiying
authors: H
authors: Lv
authors: Department of Integrated Traditional Chinese and Western Medicine, Laboratory of Ethnopharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China. Electronic address: falcontang@126.com.
authors: Tao
authors: T
authors: Tang
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000493:pharmacokinetics*; D001659:Biliary Tract; D004322:Drainage; D041743:Herb-Drug Interactions; D030004:Ligusticum; D051381:Rats; D027343:Rhizome; D014859:Warfarin / Q000493:pharmacokinetics*
chemical_list: D000925:Anticoagulants; D014859:Warfarin
keywords: Biliary drainage; Chuanxiong; Enterohepatic circulation; LC-MS/MS; Pharmacokinetics; Warfarin