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