基于生理药动学模型预测氯雷他定片在儿童体内生物等效性评价的研究  

Study on the evaluation of bioequivalence of loratadine tablets in children using physiologically based pharmacokinetic model predictionb

作　　者：江坤 王克非 刘晶晶 何仲贵[3] 刘洪卓[3] 李玉兰 王铁杰 JIANG Kun;WANG Kefei;LIU Jingjing;HE Zhonggui;LIU Hongzhuo;LI Yulan;WANG Tiejie(NMPA Key Laboratory for Bioequivalence Research of Generic Drug Evaluation,Shenzhen Institute for Drug Control,Shenzhen 518057,China;School of Pharmacy,China Medical University,Shenyang 110122,China;School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China)

机构地区：[1]深圳市药品检验研究院国家药品监督管理总局仿制药评价生物等效性研究重点实验室,广东深圳518057 [2]中国医科大学药学院,辽宁沈阳110122 [3]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2021年第10期1019-1023,共5页Journal of Shenyang Pharmaceutical University

基　　金：广东省市场监督管理局科技项目(2021CZ16);深圳市科技计划项目(JCYJ20180301170422030)。

摘　　要：目的通过氯雷他定片的体外溶出曲线数据,建立生理药动学模型,预测氯雷他定的儿童药代动力学数据,并对不同氯雷他定片在2~5岁儿童群体的生物等效性进行评价。方法采用《中国药典》2020年版的溶出方法,测定了1批氯雷他定片参比制剂和11批受试制剂的溶出曲线。利用体外溶出数据建立成人体内的生理药动学模型,并外推至2~5岁儿童,预测药动学参数,与参比制剂比较,进行生物等效性评价。结果受试制剂与参比制剂的达峰浓度(ρmax)和药时曲线下面积(AUC0→∞)相差在±20%之内,其均值的90%置信区间也落在参比制剂的80%~125%内。结论所建立的生理药动学模型能够成功预测氯雷他定片在2~5岁儿童体内的药动学行为,11种受试制剂在2~5岁儿童体内与参比制剂生物等效。Objective To predict the pharmacokinetic data and evaluate the bioequivalence of different loratadine tablets in children aged two to five years using dissolution data and GastroPlus software.Methods The dissolution curves of the 11 test preparations and one reference preparation were determined with the method described in Chinese Pharmacopeia(2020 edition).The physiologically based pharmacokinetic(PBPK)model of adult was established using in vitro dissolution data,and the model was extrapolated to children aged two to five years.The pharmacokinetic parameters were predicted by using the PBPK model of children.The bioequivalence was evaluated by comparing the pharmacokinetic parameters of test preparations with those of the reference preparation.Results The maximum concentration(ρmax)and area under the curve(AUC0→∞)of the test preparation and the reference preparation varied within±20%,and the 90%confidence interval of the mean value also fell within 80%-125%of the reference preparation.Conclusion The established PBPK model can successfully predict the pharmacokinetic behavior of loratadine tablets in children aged two to five years,and 11 tested formulations are bioequivalent to the reference formulations in children aged two to five years.

关 键 词：生理药动学模型 儿童 氯雷他定片 体外溶出 预测 

分 类 号：R917[医药卫生—药物分析学]