非线性混合效应模型法估算奥美拉唑在中国多民族中的群体药动学参数  

Population Pharmacokinetics of Omeprazole in Healthy Volunteers of Different Nationalities in China by NONMEM

作　　者：郭涛[1] 孙昨明[2] 管峥[3] 夏东亚[1] 杨璐[2] 周田彦[3] 卢炜[3] 

机构地区：[1]沈阳军区总医院药剂科,辽宁沈阳110016 [2]沈阳药科大学药学院,辽宁沈阳110016 [3]北京大学药学院,北京100191

出　　处：《解放军药学学报》2012年第5期392-395,共4页Pharmaceutical Journal of Chinese People's Liberation Army

基　　金：全军医学科学技术研究"十一五"计划科技攻关课题基金资助项目;No.06G023

摘　　要：目的建立奥美拉唑在中国多民族中的群体药动学模型,为临床个体化给药提供参考。方法汉、蒙、朝、维和回5个民族各10名(男女各半)健康志愿者口服40 mg奥美拉唑肠溶片后,HPLC测定奥美拉唑的血药浓度。应用NONMEM软件求算群体药动学参数值,建立基本模型和最终模型。考察人口统计学指标、生化指标等相关因素对药动学参数的影响,并进行模型验证。结果奥美拉唑一室模型最终的群体药动学参数CL/F、表观分布容积(V/F)和吸收常数(Ka)的群体典型值分别为20.3 L.h-1(8.08%)、44.1 L(8.91%)和3.85 h-1(12.0%)。年龄因素对V/F有显著性影响,年龄和性别因素对Ka有显著性影响。结论用NONMEM软件拟合的奥美拉唑群体药动学模型,经验证稳定可靠。Objective To establish a population pharmacokinetic （PPK） model of omeprazole in different nationalities in China in order to individualize drug therapy in chnical practice. Methods Ten healthy volunteers （5 males and 5 females） of different nationality including Han, Mongolia, Korea, Uigur and Hui were involved. All the 650 plasma concentrations of omeprazole were determined by HPLC. Basic and final models of omeprazole were developed by NONMEM software and PPK parameters were acquired. The effect of demographic and biochemical indexes were investigated. Model validations were conducted. Results The pharmacokinetics of omeprazole was described by a one-compartment pharmacokinetic model. The population typical values and relative standard errors of CL/F, V/F and Ka were 20.3 L·h^-1 （8.08%）, 44. 1 L（8.91% ） and 3.85 h^-1 （ 12.0% ）, respectively. Age had significant influence on V/F. Age and gender showed significant effect on Ka. Conclusion The final PPK model of omeprazole in five major Chinese nationalities is established by NONMEM and proves to be robust and reliable.

关 键 词：奥美拉唑 群体药动学 非线性混合效应模型 

分 类 号：R969.1[医药卫生—药理学]