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

Ethnopharmacological relevanceChuanxiong 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 studyThe 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 methodsThirty-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.ResultsThe 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).ConclusionBiliary drainage significantly influenced the disposition of warfarin, and Chuanxiong significantly affected the warfarin disposition in rat plasma.

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