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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。
Objective: To establish a method for the determination of metabolic activity of liver cytochrome P450 3A (hepatic drug CYP3A) by pharmacodynamic method. Methods: The effect of temperature on pain response was established by hot plate method. The best temperature point was found, and then different doses of midazolam were injected intravenously to establish the dose-response curve. Results: From 42 ℃ to 48 ℃, the number of lumbar hind leg increased significantly with the increase of temperature, and there was a significant dose-response relationship (r = 0.8, P <0.01). The number of jumps increased from 46 ℃ with the increase of temperature, the temperature of 48 ℃ ~ 52 ℃ changed obviously, but the temperature of 48 ℃ was the scald of the rear foot of 52 ℃ rats. Midazolam at different doses inhibited the licking and leaping reactions of hot plate rats at 48 ℃. With the increase of dosage, the number of licking and hindlimb reactions significantly decreased, with a significant dose-response relationship (r = -0.54, P <0.05) ), The incubation period also increased with increasing dose. Conclusion: This method can indirectly detect the metabolic activity of CYP3A.