卡托普利片在中国健康受试者中的生物等效性研究  

Study on the bioequivalence of captopril tablets in Chinese healthy subjects

作　　者：何亚青 张望刚 刘彩霞[2] 李昕遥 李金姑 HE Ya-qing;ZHANG Wang-gang;LIU Cai-xia;LI Xin-yao;LI Jin-gu(a.Phase I Clinical Trial Ward,Zhejiang Hospital,Hangzhou 310000,Zhejiang Province,China;Department of Nursing,Zhejiang Hospital,Hangzhou 310000,Zhejiang Province,China;Department of Cardiology,Zhejiang Hospital,Hangzhou 310000,Zhejiang Province,China;Zhongfu Pharmaceutical Co.Ltd,Weifang 261000,Shandong Province,China)

机构地区：[1]浙江医院Ⅰ期临床试验研究室,浙江杭州310000 [2]浙江医院护理部,浙江杭州310000 [3]浙江医院心内科,浙江杭州310000 [4]中孚药业股份有限公司,山东潍坊261000

出　　处：《中国临床药理学杂志》2024年第17期2548-2551,共4页The Chinese Journal of Clinical Pharmacology

摘　　要：目的评价卡托普利片受试制剂和参比制剂在中国健康受试者中的生物等效性及安全性。方法用单中心、随机、开放、双周期、双交叉设计方案,将24例健康受试者随机分成2组,在空腹状态下口服卡托普利受试制剂和参比制剂各25 mg,用液相色谱—串联质谱(LC-MS/MS)法测定卡托普利的血浆浓度,用PhoenixTM WinNonlin®(8.0版本)软件,用非房室模型拟合法计算卡托普利药代动力学参数,评价生物等效性,并进行安全性评估。结果空腹组试验中受试制剂与参比制剂卡托普利的主要药代动力学参数:Cmax分别为(803.22±196.81)和(844.75±163.43)ng·mL^(-1),AUC0-t分别为(3118.06±642.05)和(3353.53±597.94)h·ng·mL^(-1),AUC_(0-∞)分别为(3347.35±712.07)和(3594.15±654.39)h·ng·mL^(-1)。C_(max)、AUC_(0-t)、AUC_(0-∞)的几何均值比的90%置信区间(CI)分别是87.15%~99.97%、89.54%~96.14%、89.55%~96.26%,均在80.00%~125.00%。试验期间受试制剂与参比制剂不良事件发生率分别为30.43%和33.33%,未发生严重不良事件。结论卡托普利的受试制剂和参比试剂具有生物等效性,安全性良好。Objective To compare the pharmacokinetic behavior of two captopril tablets in Chinese healthy subjects,and evaluate the bioequivalence and safety of the tested and reference preparations.Methods This study was a single-center,random,open,double-cycle,double-cross design scheme.Twenty-four healthy subjects were randomized divided two groups and took single dose of 25 mg captopril of test tablet or reference tablet under fasting condition during each period.Plasma concentrations of captopril were determined by liquid chromatography-mass spectroscopy(LC-MS/MS)following administration of the oral single captopril tablet.The pharmacokinetic parameters were calculated by using non-atrioventricular model with WinNonlin 8.0 software to evaluate bioequivalence.The safety of clinical observation indexes of the subjects was evaluated during the trail.Results Main pharmacokinetic parameters of test preparation and reference preparation captopril in fasting group test:Cmax were(803.22±196.81)and(844.75±163.43)ng·mL^(-1);AUC_(0-t)were(3118.06±642.05)and(3353.53±597.94)h·ng·mL^(-1);AUC_(0-∞)were(3347.35±712.07)and(3594.15±654.39)h·ng·mL^(-1).The 90%confidence intervals(CI)of geornetric mean ratio of Cmax,AUC_(0-t)and AUC_(0-∞)were 87.15%-99.97%,89.54%-96.14%and 89.55%-96.26%,all in the range of 80.00%-125.00%,indicating that the bioequivalence of the two preparations could be determined.During the trial,the incidence rates of adverse events for the test preparation and the reference preparation were 30.43%and 33.33%,respectively,without any serious adverse events occurring.Conclusion The test tablet and reference tablet of captopril were equivalent and safe during the trial.

关 键 词：卡托普利 生物等效性 药物动力学 安全性 

分 类 号：R972[医药卫生—药品]