迭代二步法估算妥布霉素的群体药动学参数

Estimating the population pharmacokinetic parameters of tobramycin by iterative two stage method

目的 用迭代二步法估算肌注妥布霉素的群体药动学参数。方法 收集 5 6例呼吸科感染患者肌注妥布霉素的临床血药浓度监测数据 (n =15 4) ,用荧光偏振免疫法测定妥布霉素的血清浓度 ,用迭代二步法估算妥布霉素的群体药动学参数 ,比较性别、年龄、体重、肌酐清除率 (CLcr)等因素对药动学参数的影响。结果 5 6例的CL为 (75 .6 5± 16 .88)mL·h-1·kg-1,Vd 为(0 .2 6 13± 0 .0 438)L·kg-1,t1/2 为 (2 .46± 0 .5 1)h。性别对药动学参数没有影响 ,年龄 >5 0岁时CL下降 ,Vd 与体重呈正相关 ,CL与CLcr呈正相关。结论 迭代二步法能较好地估算出有代表性的妥布霉素的群体药动学参数 。

OBJECTIVE To estimate the population pharmacokinetic parameters of tobramycin by iterative two stage method. METHOD The clinical data(n = 154) were collected from 56 patients with respiratory tract infection receiving tobramycin by intramuscular injection. The concentrations of tobramycin in serum were determined by fluorescence polarization immunoassay. The population pharmacokinetic parameters were estimated by iterative two stage method. The influence of sex, age, body weight and creatinine clearance on pharmacokinetics was investigated. RESULTS The population pharmacokinetic parameters in 56 patients were CL(75.65 ± 16.88) mL·h-1·-kg-1, Vd(0.2613 ± 0.0438) L·kg-1 and t1/2(2.46 ± 0.51) h respectively. The pharmacokinetic parameters of tobramycin were shown to be influenced by age, body weight and creatinine clearance. CONCLUSION Iterative two stage method is suitable for estimating population pharmacokinetic parameters, optimizing individualizing dosage regimens and forecasting plasma concentration of medications.