【摘要】 目的:用药效学方法建立肝脏细胞色素P450 3A(肝药酶CYP3A)代谢活力测定方法。方法:采用热板法建立鼠随温度变化疼痛反应变化的量效关系,寻找最佳的温度点,然后给予鼠静脉注射不同剂量的咪达唑仑,建立量效关系曲线。结果:从42℃至48℃,随着温度的升高,舔后足次数明显增加,存在明显的量效关系(r=0.8,P<0.01)。跳跃次数从46℃开始随温度的增加而增加,变化明显的温度在48℃至52℃,但52℃鼠后足已经烫伤,最佳刺激温度为48℃。不同剂量咪达唑仑对48℃热板鼠舔足反应、跳跃反应有抑制作用,随剂量的增加,舔后足反应次数明显减少,存在明显的量效关系(r=-0.54,P<0.05),潜伏期也随着剂量的增加而延长。结论:此方法能够间接检测CYP3A的代谢活力。更多还原

【Abstract】 Objective: To establish the determination method of metabolic activity of liver drug enzyme cytochrome P450 3A(hepatic enzyme CYP3A) by pharmacodynamics.Methods: The hot plate method was taken to establish quantity-efficiency relation of the changes in rats’ pain responses with changes in temperature,searching for the optimal temperature point,and then different doses of MDZ(intravenous injection) was given to rats to set up quantity-efficiency relation curve.Results: There was a significant increase in the frequency of rats’ licking the hind foot with a rise in the temperature from 42 ℃ to 48 ℃,with a remarkable dose-effect relation(r=0.8,P﹤0.01).There was an increase in the frequency of rats’ jump with a rise in the temperature from 46 ℃,remarkably at the temperature of 48 ℃ to 52 ℃.Since the rats’ feet were scalded at 52 ℃,the optimal stimulation temperature is 48 ℃.Midazolam of different doses had an inhibition effect on rats’ response of paw licking and jumping at 48 ℃ hot plate.With the increase in the dose,there was a significant decrease in the frequency of rats’ licking hind foot reaction,with a remarkable dose-effect relation(r=-0.54,P﹤0.05).latency was prolonged with the increase in the dose.Conclusion: This method is capable of detecting CYP3A metabolism vigor.更多还原