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

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• 作者：Haigang Li<sup>asup><sup> ; sup><sup>bsup> ; Chunhu Zhang<sup>asup> ; Rong Fan<sup>asup> ; Hua Sun<sup>csup> ; Haitang Xie<sup>csup> ; Jiekun Luo<sup>asup> ; Yang Wang<sup>asup><sup> ; sup><sup>wangyang_xy87@163.com" class="auth_mail" title="E-mail the corresponding authorsup> ; Huiying Lv<sup>dsup><sup> ; sup><sup>117324662@qq.com" class="auth_mail" title="E-mail the corresponding authorsup> ; Tao Tang<sup>asup><sup> ; sup><sup>falcontang@126.com" class="auth_mail" title="E-mail the corresponding authorsup>
• 关键词：Warfarin ; Chuanxiong ; Pharmacokinetics ; Enterohepatic circulation ; LC-MS/MS ; Biliary drainage
• 刊名：Journal of Ethnopharmacology
• 出版年：2016
• 出版时间：4 December 2016
• 年：2016
• 卷：193
• 期：Complete
• 页码：117-124
• 全文大小：1312 K

文摘

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.

sSec_2">Aim of the study

sp0040">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.

sSec_3">Materials and methods

sp0045">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.

sSec_4">Results

sp0050">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<sub>0&minus;tsub>), peak concentration (C<sub>maxsub>), total plasma clearance (CLz/F) and mean residence time (MRT<sub>0&ndash;tsub>) between the WCO and WCN groups; the AUC<sub>0&ndash;tsub> 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<sub>maxsub> compared the WO group (p<0.01).

sSec_5">Conclusion

sp0055">Biliary drainage significantly influenced the disposition of warfarin, and Chuanxiong significantly affected the warfarin disposition in rat plasma.