生理药动学模型预测国产头孢拉定颗粒体外溶出特性及对体内药动学影响  

Study on the dissolution characteristics of domestic cefradine granules in vitro and its influence on pharmacokinetics in vivo using physiologically based pharmacokinetics model prediction

作　　者：张斗胜[1] 王晨[1] 姚尚辰[1] 胡昌勤[1] ZHANG Dou-sheng;WANG Chen;YAO Shang-chen;HU Chang-qin(National Insititues for Food and Drug Control, Beijing 102629 , China)

机构地区：[1]中国食品药品检定研究院,北京102629

出　　处：《中国新药杂志》2019年第5期536-540,共5页Chinese Journal of New Drugs

基　　金：国家"重大新药创制"科技重大专项资助项目(2015ZX09303001);北京市科技计划课题资助项目(Z151100000115013)

摘　　要：目的:预测国产不同头孢拉定颗粒体外溶出特性及对体内药动学的影响。方法:根据不同厂家产品的体外溶出结果拟合体内溶出释放曲线;采用Gastroplus软件建立生理药动学模型;虚拟群体模拟预测制剂体外溶出特性以及对体内药动学的影响。结果:目前国产头孢拉定颗粒在45 min内溶出量(Q)达85%以上(T_(85%)=45 min),达峰浓度(C_(max))、药时曲线下面积(AUC_(0→∞))等主要药动学参数仍落在85%～125%内;不同厂家颗粒的体外溶出差异未影响体内药动学特征。结论:国产头孢拉定颗粒体外呈快速溶出的特性;快速溶出有利于其在体内迅速吸收,是发挥药效的有利因素。Objective:To predict dissolution characteristics of different domestic cefradine granules in vitro and their effects on pharmacokinetics in vivo.Methods:Fit the release rate curve in vivo according to the dissolution results of product from different manufacturers in vitro.Physiological pharmacokinetic model was established by Gastroplus software,the dissolution characteristics of the preparation in vitro and the effects on pharmacokinetics in vivo were predicted by virtual population simulation.Results:At present,the dissolution rate(Q)of domestic cefradine granules in 45 min is predicted to be over 85%(T85%=45 min),the main pharmacokinetic parameters(Cmax,AUC0→∞and so on)were still between 85%and 125%.It does not affect the pharmacokinetic characteristics in vivo when the dissolution of granules from different manufacturers is different in vitro.Conclusion:The domestic cefradine granules are rapid dissolution in vitro,which is beneficial for its rapid absorption in vivo and is an advantageous factor to exert the efficacy of drugs.

关 键 词：生理药动学模型 头孢拉定颗粒 体外溶出 影响 预测 

分 类 号：R917[医药卫生—药物分析学]