【摘要】 目的:研究山奈酚在大鼠体内对硝苯地平药物动力学的影响,揭示山奈酚与临床心血管药物相互作用的有关信息。方法:将20只雄性SD大鼠随机分成4组,山奈酚组分别经口给予山奈酚5、10、15 m g/kg和硝苯地平10 m g/kg,对照组只给硝苯地平。用反相高效液相法测定不同时间点的硝苯地平血浆浓度,根据测定结果计算硝苯地平的药物动力学参数。结果:山奈酚3个剂量组硝苯地平的血药峰浓度分别为0.51、0.70和0.81μg/m l,浓度曲线下面积分别是1.81、2.83和3.63μg/(h.m-l 1),平均保留时间分别是3.66、3.87和4.07 h,与对照组比较均有显著升高(P<0.01);而达峰时间以及消除半减期则与对照组之间没有显著性差异。结论:在大鼠体内山奈酚可抑制硝苯地平的代谢,改变硝苯地平的药物动力学参数。更多还原

【Abstract】 Objective: To investigate the effect of kaempferol on the pharmacokinetics of nifedipine（NFP） in rats.Methods: Twenty male SD rats,weighing 220～260 g,were distributed randomly into 4 groups.The animals were fasted,but allowed free access to water for 12 h before the administration of drugs.NFP dissolved in corn oil was administered via gastric intubation to the rats in control group at a dose of 10 mg/kg.Kaempferol was administered orally to the other three groups with dose of 5,10,15 mg/kg,respectively,followed by oral administration of NFP 10 mg/kg.Blood samples were collected through tail vein in heparinized plastic microcentrifuge tubes before and after drug administration.The plasma concentration of NFP was monitored with reversed phase high-performance liquid chromatography（RP-HPLC）.Nimodipine was used as the internal standard.Statistical data evaluation was performed with Student’s t-test and one-way analysis of variances.Results: The maximal plasma concentration(C_max) of the three treated groups were 0.51,0.70 and 0.81 μg/ml,respectively.The area under the concentration-time curve(AUC_0-8) were 1.81,2.83 and 3.63 μg/(h·ml^-1),respectively.The C_max,AUC_0-8 and the mean retention time(MRT_0-8) of NFP were significantly increased by simultaneous oral treatment with kaempferol（P<0.01）.On the other hand,there were no significant differences in the mean peak value time in plasma(T_max) and the elimination half-life(t_1/2（ke）) between the control and the treated groups.Conclusion: The concomitant oral use of kaempferol with NFP may influence the pharmacokinetic parameters of NFP in rats,which suggests that kaempferol might reduce the first-pass metabolism of NFP.更多还原