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建立丙戊酸钠在中国癫(疒间)患者中的群体药代动力学模型
钱金1,陈顺2,谢新芳2,游春华2,高守红2*
0
(1. 第二军医大学长海医院药学部, 上海 200433;
2. 第二军医大学长征医院药学部, 上海 200003
*通信作者)
摘要:
目的 建立中国癫(疒间)患者服用丙戊酸钠的群体药代动力学模型,促进个体化合理给药。方法 收集69例癫(疒间)患者服用丙戊酸钠后的血药浓度监测数据和临床资料。应用Phoenix NLME软件建立群体药代动力学模型(n=101,选择比例型残差模型表示),考察协变量(性别、年龄、体质量、合并用药等)对吸收速率常数(Ka)、表观分布容积(Vd)与清除率(CL)的影响。通过自举法对最终模型进行验证及评价(n=500)。结果 群体药代动力学最终模型为:TvKa=2.38,V=TvV,CL=TvCL·exp(ηCL)。自举500次验证模型,结果显示稳健率100%,得到的参数平均值、中位数均与模型参数结果一致,说明模型比较稳定;年龄、性别、体质量、合并用药等变量无法引入最终模型中。结论 本研究建立的群体药代动力学模型与基础模型一致,可为临床合理的个体化给药提供依据。
关键词:  丙戊酸钠  群体药代动力学模型  phoenix NLME  癫(疒间)
DOI:10.16781/j.0258-879x.2017.11.1449
投稿时间:2017-05-03修订日期:2017-08-24
基金项目:国家自然科学基金(81302856),上海市科学技术委员会计划项目(13ZR1413800).
Establishment of a population pharmacokinetic model of sodium valproate in patients with epilepsy in China
QIAN Jin1,CHEN Shun2,XIE Xin-fang2,YOU Chun-hua2,GAO Shou-hong2*
(1. Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai 200433, China;
2. Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
*Corresponding author)
Abstract:
Objective To establish a population pharmacokinetic model of sodium valproate in patients with epilepsy in China, so as to promote individualized drug administration. Methods The plasma concentrations and clinical data were collected from 69 patients with epilepsy after receiving sodium valproate. Population pharmacokinetic model (n=101, showed by proportional residual model) was established using Phoenixs NLME software, and the effects of covariate (gender, age, body weight, drug combination and so on) on absorption rate constant (Ka), distribution volume (Vd) and clearance (CL) were estimated. The final model was validated and evaluated by Bootstraps (n=500). Results The final population pharmacokinetic model was:TvKa=2.38, V=TvV, CL=TvCL·exp(ηCL), and the robust rate was 100% as displayed by the Bootstrap. The average value and median of parameters obtained by Bootstrap were consistent with the model parameters, indicating that the model was relatively stable. Age, gender, body weight, drug combination and other variables were not introduced into the final model. Conclusion The population pharmacokinetic model established in this study is consistent with the basic model, providing reference for rational individualized drug administration in clinical practice.
Key words:  sodium valproate  population pharmacokinetics model  phoenix NLME  epilepsy