度洛西汀在中国健康受试者中的群体药代动力学研究

Population pharmacokinetics of duloxetine in Chinese healthy subjects

目的 建立度洛西汀在中国受试者中的群体药代动力学模型。方法 基于36例健康受试者单次/多次服用盐酸度洛西汀肠溶片后密集采样的数据,使用NONMEM软件建立度洛西汀的群体药代动力学模型,通过前进法和后退法考察性别、年龄、体质量、白蛋白、血肌酸酐、谷丙转氨酶和剂量对药代动力学参数的影响。模型验证包括拟合优度图、可视化检验和自举法。结果 度洛西汀的群体药代动力学模型为一级消除的一房室模型,吸收特征由转移室模型描述,剂量为清除率的协变量。清除率、分布容积、平均转移时间和转移室个数的个体间变异分别为54.71%、56.86%、27.30%和87.71%。结论 转移室模型更合理地描述度洛西汀在中国受试者中的吸收特征。

Objective To establish a population pharmacokinetic(PPK) model of duloxetine in Chinese subjects.Methods Based on the data of intensive sampling of duloxetine hydrochloride enteric coated tablets in 36 healthy subjects after single/multiple administrations,a PPK model of duloxetine was established using NONMEM software.The effects of gender,age,body weight,albumin,serum creatinine,glutamic pyruvic transaminase and dose on pharmacokinetic parameters were investigated by stepwise forward and backward methods.Model validation includes goodness of fit,visual prediction check and bootstrap.Results The PPK model of duloxetine was a one compartment model with first-order elimination and the absorption characteristics were described by the transit model,and the dose was a covariate of clearance.The inter-individual variability of clearance,volume of distribution,mean transit time and number of transit compartments were 54.71%,56.86%,27.30% and 87.71%,respectively.Conclusion The transit model more reasonably describes the absorption characteristics of duloxetine in Chinese subjects.