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

    • 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/FTmax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-∞), Cmax were significantly rose (P<0.05) while CL/F and Tmax 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.

       

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