| Summary: | Haigang Li,1,2 Yang Wang,1 Rong Fan,1 Huiying Lv,3 Hua Sun,4 Haitang Xie,4 Tao Tang,1 Jiekun Luo,1 Zian Xia1 1Department of Integrated Traditional Chinese and Western Medicine, Laboratory of Ethnopharmacology, Xiangya Hospital, Central South University, 2Department of Pharmacy, Changsha Medical University, 3Hunan Agricultural Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha, 4Anhui Provincial Centre for Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu, People’s Republic of China Abstract: According to previous research studies, warfarin can be detected in human bile after oral administration. Ferulic acid (FA) is the main bioactive component of many Chinese herbs for the treatment of cardiovascular disease. To elucidate the effects of FA on the pharmacokinetics of warfarin in rats after biliary drainage is necessary. Twenty rats were randomly divided into four groups: Group 1 (WN): healthy rats after the administration of warfarin sodium, Group 2 (WO): a rat model of biliary drainage after the administration of warfarin sodium, Group 3 (WFN): healthy rats after the administration of warfarin sodium and FA, and Group 4 (WFO): a rat model of biliary drainage after the administration of warfarin sodium and FA. Blood samples were collected at different time points after administration. The concentrations of blood samples were determined by ultraperformance liquid chromatography–tandem mass spectrometry. Comparisons between groups were performed according to the main pharmacokinetic parameters calculated by the DAS 2.1.1 software. The pharmacokinetic parameters showed a significant difference between the WN and WO groups, the WO group showed a decrease of 51% and 41.6% in area under the curve from 0 to time (AUC0–t) and peak plasma concentration (Cmax), respectively, whereas time to Cmax (Tmax) was delayed 3.27 folds. There were significant differences between the WFO and WFN groups, the WFO group showed a decrease of 63.8% and 70% in AUC0–t and Cmax, respectively; the delay in Tmax between the WN and WFN groups (mean, from 132–432 minutes) was significantly different; the mean retention time from 0 to time (MRT0–t) between the WO and WFO groups (mean, from 718.31–606.13 minutes) also showed a significant difference. Enterohepatic circulation markedly influences the disposition of warfarin in rats, and FA significantly affected the warfarin disposition in rat plasma. Keywords: warfarin, ferulic acid, pharmacokinetics, enterohepatic circulation, UPLC-MS/MS, biliary drainage
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