基于NONMEM法构建美罗培南群体药代动力学模型  

Population Pharmacokinetic Modeling of Meropenem by Nonlinear Mixed Effects Model

作　　者：吴京南 刘亦伟[1] 许建文 王长连[1] WU Jing-nan;LIU Yi-wei;XU Jian-wen;WANG Chang-lian(Department of Pharmacy,Affiliated First Hospital of Fujian Medical University,Fuzhou 350001,China)

机构地区：[1]福建医科大学附属第一医院药学部,福建福州350001

出　　处：《海峡药学》2020年第8期41-45,共5页Strait Pharmaceutical Journal

基　　金：福建医科大学教授基金(编号JS10012)。

摘　　要：目的建立国人美罗培南群体药代动力学(population pharmacokinetic,PPK)模型,为抗菌药物药物的合理使用提供理论支持。方法收集101例使用美罗培南治疗患者的172个稳态血药浓度,限制性片段长度多态性聚合酶链反应检测MDR1 C3435T。非线性混合效应模型法考察病理生理特征和联合用药对美罗培南药代动力学参数的作用,建立最终模型。并通过拟合优度诊断、自举法(Bootstrap)及正态预测分布误差法验证美罗培南PPK模型。结果美罗培南表观清除率(CL)及表观分布容积(Vd)的群体值分别为14.3L·h^(-1)和24.9L,患者内生肌酐清除率显著影响美罗培南的清除率,经验证美罗培南PPK模型稳定、有效。结论美罗培南PPK最终模型具有较好的预测能力和稳定性,可为美罗培南临床用药方案的制定提供理论依据。OBJECTIVE To establish a population pharmacokinetic model of meropenem in Chinese people,then provide theoretic supports for individualized administration.METHODS HPLC method was used to monitor the 172 plasma concentrations that were collected from 101 patients.PCR-RFLP technique was used to genotype the MDR1 C3435T.The population pharmacokinetic model of meropenem which investigated the effect of MDR1 C3435T genotype,co-therapy drugs,physiological and pathological factors on pharmacokinetic parameters was established using NONMEM.The validation and reliability of final PPK model was evaluated by diagnosis,Bootstrap and NPDE verification.RESULTS The population estimate of apparent clearance and apparent volume was 14.3L·h-1 and 24.9L,respectively.The clearance was significantly associated with creatinine clearance.CONCLUSION The final model is stable and effective,which can be used for individualized drug therapy of meropenem.

关 键 词：美罗培南 群体药代动力学 非线性混合效应模型 

分 类 号：R969.4[医药卫生—药理学]