Haigang Li1, Chunhu Zhang2, Rong Fan2, Hua Sun3, Haitang Xie3, Jiekun Luo2, Yang Wang4, Huiying Lv5, Tao Tang6. 1. 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. 2. Department of Integrated Traditional Chinese and Western Medicine, Laboratory of Ethnopharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China. 3. Anhui Provincial Centre for Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu 241001, PR China. 4. 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. 5. Hunan Agricultural Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha 410125, PR China. Electronic address: 117324662@qq.com. 6. 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.
Abstract
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 0.5mg/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-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.
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 0.5mg/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-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.