临床药代动力学中蓄积指数的计算方法及其评价

Evaluation and calculation of the accumulation index in clinical pharmacokinetics

目的:多次给药的蓄积一般由药动学的蓄积指数(Rac)来表达,但计算Rac有多种方法,本文对此进行分析和评价,以确定合理的方法。方法:计算机模拟蒿乙醚真实实验的单、多次给药的血药浓度经时变化,分别采用AUC法、Cmax法、Ctrough法和模型法计算Rac,采用Bootstrap抽样法评价各法的优缺点及适用条件。结果:AUC法和Cmax法较Ctrough法和模型法更为稳定,模型法计算值偏高。药效或毒性呈浓度依赖性者,宜用Cmax法,而药效或毒性时间依赖性和体内药量依赖性时,宜用AUC法。结论:药物蓄积与有效性和安全性均相关,Rac计算方法需根据药物特性进行合理选择。

AIM： To analyze and evaluate the accumulation index （Rac） in clinical pharmacokinetics of multiple dosing administrations in order to obtain one reasonable method. METHODSThe plasma concentration-time data of arteether was simulated for 1000 subjects in multiple doses administration. The 20-40 subjects were sampled for 1000 time by the Boostrap method and values of Rac were calculated by the AUC, C Ctro.gh and model. The values of Rac were evaluated by their distributions. RESULTS：The AUC and Cmax method were more stable than the Ctrough and model method. If the efficacy or toxicity was related with the concentration, it was appropriate to use the Cmax method, and if the efficacy or toxicity was related with the time, it was appropriate to use the AUC method. CONCLUSION. The drug accumulation is related with effectiveness and safety, and the reasonable choice of Rac calculation method should be based on drug and data characteristics.