摘要:
目的 建立中国人群中西布曲明的群体药动学模型.方法 20例男性健康志愿者口服10 mg西布曲明,于服药后0～24 h采集13个采样点采血,采用已验证的HPLC法测定血药浓度.采用非线性混合效应模型(NONMEM)进行群体药动学分析,估算药动学参数.以直观预测检验(Visual predictive check,VPC)和正态预测分布误差(Normalized predictive distribution error,NPDE),Bootstrap法进行模型性能评估.结果 以有吸收时滞的一级吸收和消除的二
Abstract:
objective To develop the population pharmacokinetics model of sibutramine (SIB) in Chinese healthy volunteers.Methods Twenty male healthy volunteers were enrolled into the study.13 blood sampling were drawn after administration of 10 mg SIB within 24h.Theplasma samplesfor SIB concentration were analyzed using validated HPLC/MS method.The population pharmacokinetics was characterized by non-linear mixed effects model (NONMEM).Visual predictive check (VPC) and normalized predictive distribution error (NPDE) were used to evaluate the predictive ability of the model.The reliability and stability of the population pharmacokinetic model developed was further assessed by a nonparametric bootstrap procedure,Results A two-compartment pharmacokinetic model with first-order absorption and elimination was used to describe the concentration-time data.The weight and age had no significant impact on the model parameters.The population typical values (inter-individual variability) of Vl,V2,CL,Q,Ka and Tlag were 7.85 (42.8%) L,2.03 (48.2%)L,1.08 (38.5%)L/h,0.289 (27.1%)L/h,1.95 (56.8%)h～and 0.187 (17.8%)h respectively.Most of parameter estimates from non-parametric bootstrap procedure were comparable and within 10% of the estimates from NONMEM.The stability and the predictive performance were accepted by Bootstrapping,the goodness-of-fit,VPC and NPDE.Conclusion The final population pharmacokinetics model of SIB in Chinese healthy was established by NONMEM,The modcl was steady and reliable.
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