用药理效应研究曲马朵对小鼠镇痛作用的药代动力学

Pharmacologic effect in studying pharmacokinetics of tramadol’s analgesic actions in mice

目的 :探讨曲马朵在小鼠体内镇痛作用的药代动力学。方法 :采用药效 -药代结合模型 ,以小鼠腹腔注射醋酸后扭体反应次数为镇痛效应指标 ,计算给药后不同时间间隔及不同给药剂量下的镇痛百分率 ,测定时 -效、量 -效关系 ,进一步求时间 -体存生物相当药量曲线及相应药代动力学参数。结果 :曲马朵对小鼠的镇痛作用呈显著的时 -效、量 -效关系 ,其镇痛作用效量半衰期 T1 /2 ( ED) 为 4 .6 8min,消除速率常数 K为 0 .14 8。 结论 :曲马朵母核药物与其多种代谢中间产物均有镇痛作用 ,此法比单纯测定曲马朵的血药浓度更能科学地反映药物在作用部位的药效变化规律。

Objective:To study pharmacokinetics of tramadol's analgesic actions in mice. Methods:Using the pharmacodynamic pharmacokinetic combined model, the analgesic action of tramadol was quantized by detecting twistering feedback in mice after coeli injection of acetic acid. After administration of different dose and with different time interval of tramadol, the pharmacokinetics parameters were determined by measuring the dose dependent and time course effects of tramadol's analgesic actions. Results:Notable dose dependent and time course effect of tramadol analgesia was found in mice, and effect dosage half life period(T 1/2ED ) was 4.68 min; Constant of eliminating rate(K) was 0.148. Conclusion:The pharmacodynamic pharmacokinetic combined model used in this study is more scientific than the traditional method by detecting the plasma concentration of tramadol, because both tramadol and its metabolites have the similar analgesic actions.