Zhou Yun, Song Xiaoli, Dong Gang
a Department of Pharmacy , Yidu Central Hospital of Weifang , Shandong , China.
Xenobiotica. 2019 Oct;49(10):1178-1182. doi: 10.1080/00498254.2018.1518552. Epub 2019 Jun 11.
The oral bioavailability of puerarin is poor which hindered its clinical performance. This study investigates the effects of verapamil on the pharmacokinetics of puerarin in rats. The pharmacokinetics of orally administered puerarin (50 mg/kg) with or without verapamil pretreatment (10 mg/kg/day for 7 days) were investigated. The plasma concentration of puerarin was determined using LC-MS/MS method, and the pharmacokinetics profiles were calculated and compared. Caco-2 cell transwell model was also used to investigate the effects of verapamil on the transport pf puerarin. The results showed that when the rats were pretreated with verapamil, the maximum concentration () of puerarin increased from 683.7 ± 51.2 to 933.5 ± 75.8 ng/mL ( < 0.05), and the area under the concentration-time curve from zero to infinity (AUC) also increased from 3687.3 ± 444.6 to 5006.1 ± 658.6 μg·h/L ( < 0.05). The Caco-2 cell transwell experiments indicated that verapamil could decrease the efflux ratio of puerarin from 1.90 to 1.19 through inhibiting the activity of . In conclusion, these results indicated that verapamil could affect the pharmacokinetics of puerarin, possibly by increasing the systemic exposure of puerarin by inhibiting the activity of .
葛根素的口服生物利用度较差，这限制了其临床应用。本研究考察了维拉帕米对大鼠体内葛根素药代动力学的影响。研究了口服葛根素（50 mg/kg）且有或无维拉帕米预处理（10 mg/kg/天，共7天）的药代动力学情况。采用LC-MS/MS法测定葛根素的血浆浓度，并计算和比较药代动力学参数。还使用Caco-2细胞Transwell模型考察维拉帕米对葛根素转运的影响。结果表明，维拉帕米预处理大鼠后，葛根素的最大浓度（）从683.7±51.2 ng/mL增加至933.5±75.8 ng/mL（<0.05），零至无穷大的浓度-时间曲线下面积（AUC）也从3687.3±444.6 μg·h/L增加至5006.1±658.6 μg·h/L（<0.05）。Caco-2细胞Transwell实验表明，维拉帕米可通过抑制的活性将葛根素的外排率从1.90降至1.19。总之，这些结果表明维拉帕米可能通过抑制的活性增加葛根素的全身暴露，从而影响葛根素的药代动力学。
