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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。
Objective To study the pharmacokinetics of losartan and its metabolite E-3174 in rats after long-term administration of ferulic acid. Methods Twelve healthy male SD rats were randomly divided into 2 groups (6 rats in each group). The experimental group was fed with ferulic acid (50 mg · kg -1) daily for 7 days and the control group was given 0.5% CMC-Na. Losartan (5 mg · kg -1) was administered 30 min after the eighth day. Blood samples were taken from the tail vein of rats before administration and at 0.25,0.5,0.75,1,1.5,2,3,4,6,8,10,12,24 h after administration. The blood samples were collected by UPLC-MS / MS detection of plasma concentrations of losartan and E-3174. Results Although the pharmacokinetic parameters of Losartan in two groups were not statistically significant, the AUC (0-t), AUC (0-∞) and Cmax of E-3174 in the experimental group were significantly increased (P <0.05), and the CL / F and Tmax were significantly decreased (P <0.05). CONCLUSION: Long-term administration of ferulic acid in rats failed to induce changes in the pharmacokinetics of losartan. However, metabolism of E-3174 slowed down and the concentration increased. The area under the curve increased with time.