阿魏酸长期给药后对大鼠灌服氯沙坦钾的药动学影响

Effects of Ferulic Acid on the Pharmacokinetics of Intragastrically Administered Losartan in Rats

关键词:  阿魏酸  氯沙坦  E-3174  UPLC-MS/MS

Key words:  ferulic acid  losartan  E-3174  UPLC-MS/MS

摘要:

目的 研究长期给药阿魏酸对大鼠体内氯沙坦及其代谢物E-3174的药动学影响。方法 12只健康♂ SD大鼠随机分成2组（每组6只），试验组每天灌胃50 mg·kg^-1阿魏酸，连续诱导7 d；对照组灌胃等体积0.5%CMC-Na。第8天给药30 min后，给予氯沙坦钾（5 mg·kg^-1）。分别于给药前和给药后0.25，0.5，0.75，1，1.5，2，3，4，6，8，10，12，24 h大鼠尾静脉取血，血样处理后采用UPLC-MS/MS检测大鼠血浆中氯沙坦及E-3174的浓度。结果 虽然2组大鼠体内氯沙坦各项药动学参数对比均无统计学意义，但是试验组大鼠体内E-3174的AUC（0-t）、AUC（0-∞）和Cmax显著增高（P<0.05）；CL/F、Tmax显著降低（P<0.05）。结论 大鼠长期给药阿魏酸后虽然未能引起氯沙坦原形药物药动学的变化，但可使其活性代谢产物E-3174代谢减慢，浓度增高，药时曲线下面积增大。

Abstract:

OBJECTIVE To study the influence of ferulic acid on the pharmacokinetics of losartan and E-3174 in rats. METHODS Twelve rats (six for each group) were administered orally with 50 mg·kg^-1 ferulic acid (experimental group) or 0.5% CMC-Na (control group) every day for 7 d. On the eighth day, losartan (5 mg·kg^-1) was given to all rats orally 30 min after taking ferulic acid or CMC-Na. Blood samples were collected from the tail vein before giving losartan and at the time points of 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 h after administration. The plasma concentrations of losartan and E-3174 were determined by UPLC-MS/MS. RESULTS There was no significant difference on the pharmacokinetic parameters of losartan between the control group and the experimental group. However, the pharmacokinetic parameters of E-3174 in the experimental group, such as AUC_(0-t), AUC_(0-∞), C_max were significantly rose (P<0.05) while CL/F and T_max were significantly decreased (P<0.05) compared with the control group. CONCLUSION This study indicates that the pharmacokinetics of E-3174 in rats can be greatly changed by ferulic acid, slow down the metabolism and increase the concentration. However, ferulicacid has no effect on that of losartan.