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目的建立中国健康男性志愿者单剂量口服盐酸氨溴索的群体药物动力学模型,为临床个体化给药提供依据。方法18名男性健康志愿者随机交叉口服60 mg盐酸氨溴索片或颗粒后,采用GC-ECD测定血药浓度,用非线性混合效应模型(NONMEM)程序建立盐酸氨溴索的群体药物动力学模型,并进行模型验证评价。结果带有滞后时间的零级协同一级吸收一室模型对数据拟合良好,药物动力学参数CL/F、V/F和Ka的群体典型值及其相对标准误差分别为21.0 L.h-1(2.05%)、181.0 L(2.04%)和0.959 h-1(16.0%)。采用自举法(Bootstrap)对模型稳定性进行检验,1 000次采样结果显示收敛成功率高于90%。结论用NONMEM软件拟合建立的盐酸氨溴索群体药动学模型,参数合理,模型稳定可靠。
Objective To establish a population pharmacokinetic model of ambroxol hydrochloride in healthy male volunteers in China and provide the basis for individual clinical administration. Methods Eighteen male volunteers were randomized to oral administration of ambroxol hydrochloride tablets or granules at 60 mg / kg. The plasma concentrations of ambroxol hydrochloride tablets were determined by GC-ECD. The population pharmacokinetics of ambroxol hydrochloride was established by nonlinear mixed effect model (NONMEM) Model, and model validation evaluation. Results The zero-order synergistic primary absorption one-compartment model with lag time fitted the data well. The typical values of CL / F, V / F and Ka populations and their relative standard errors were 21.0 Lh-1 ( 2.05%), 181.0 L (2.04%) and 0.959 h-1 (16.0%). Bootstrap method was used to test the stability of the model. The result of 1 000 sampling showed that the success rate of convergence was higher than 90%. Conclusion The pharmacokinetic model of ambroxol hydrochloride was fitted by NONMEM software. The parameters were reasonable and the model was stable and reliable.