曲马多对小鼠镇痛作用的药物代谢动力学研究

Pharmacokinetic studies of tramadol′s analgesic action in mice

目的 探讨曲马多在小鼠体内的药物代谢动力学。方法 采用药效—药代统一模型 ,以小鼠腹腔注射醋酸后扭体反应次数为镇痛效应指标 ,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 曲马多在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 68min ,消除速率常数K为 0 1 4 8。结论 曲马多母核药物与多种代谢产物均有镇痛作用 。

Objective To determine pharmacokinetic data of tramadol in mice.Methods Using a united pharmacodynamic pharmacokinetic model,the analgesic action of tramadol was quantified by detecting the number of twisting motion in mice after coelo injection of acetic acid.The pharmacokinetic parameters were determined by observing the time effect and dose effect relationship of tramadol.Results Notable dose effect and time effect relationship of tramadol′s analgesia was seen in mice,its effective dose half life (T 1/2ED ) was 4 68 min;elimination rate constant (K) was 0 148.Conclusion Tramadol itself and its several metabolites have similar analgesic action,the method with united pharmacodynamic pharmacokinetic model is more efficient than those conventional ones which only detect tramadol′s blood level,while this method could reveal the pharmacodynamic changes of tramadol in each target locus.