摘要
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 construct a population pharmacokinetic model of ambroxol hydrochloride in Chinese healthy male subjects by NONMEM for individualized treatment. METHODS A single oral dose of 60 mg ambroxol hydrochloride in tablet or gran- ular formulation was given to 18 healthy male subjects in a randomized crossover study. Gas chromatography with ECD detector method was developed to determine the concentration of ambroxol hydrochlofide in human plasma. The population pharmacokinetie model of ambroxol hydrochlofide was developed via NONMEM approach. Bootstrap method was applied to evaluate the model stability. RESULTS A one-compartment model with first and zero-order simultaneous absorption process was built as the structure model. The population typical values and relative standard errors of CL/F, WF and Ka were 21.0 L · h^-1 （2.05%）, 181.0 L （2.04%） and 0.959 h^-1 （ 16. 0% ） , respectively. The success rate of bootstrap analysis was higher than 90% , indicating that the model was stable. CONCLU- SION The population pharmacokinetie model of ambroxol hydrochloride by NONMEM was proved to be robust and reliable.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2012年第3期218-222,共5页
Chinese Pharmaceutical Journal
