NONMEM法分析临床病人静脉输注阿米卡星的群体药代动力学

ANALYSIS OF POPULATION PHAKMACOKINETICS WITH NONMEM IN CLINICAL PATIENTS TREATED WITH AMIKACIN BY INTRAVEN0US INFUSION

摘要: 收集52例呼吸科感染病人静脉输注阿米卡星(amikacin,AMK)的临床数据,用荧光偏振免疫法(FPIA)测定临床病人AMK的血清浓度275点,按二房室开放模型,用NONMEM程序一步估算出AMK的群体药代动力学参数,并定量地分析病人的体重、肌酐清除率、长期用药和病理状况(慢性阻塞性肺病,COPD)等固定效应对药代动力学参数的影响。经统计分析病人的肌酐清除率和COPD对AMK的药代动力学参数的影响有显著意义,而体重对表观分布容积Vc的影响无显著意义。由最终回归模型估算出AMK的群体药代动力学参数。

Abstract: CIinical data(n=275)collected from 52 patients with respiratory tract infectionreceiving amikacin(AMK)by intravenous infusion were analysed with NONMEM,a computerprogram designed for estimating population phannacokinetic parameters.COncentrations of AMK inserum were detennined by fluorescence polarization immunoassay(FPIA).A two compartment openmodel was used for analysing AMK population phannacokinetics.The influence of bedy weight(BW),creatinine clearance(CC),administration history(HIS)and state of pathology(chronicobstructional pulmonary diSease,COPD)on pharmacokinetics was investigated.The pharn1acokinetic parameters of AMK were shown to be influenced by creatinine clearance(CC)and COPD.