单硝酸异山梨酯缓释片在健康人中的药代动力学与相对生物利用度研究  

Pharmacokinetic and relative bioavailability of isosorbide mononitrate sustained-release tablets in healthy volunteers

作　　者：吴茂锋 谭晓明[1] 刘冉冉 麦长凤 刘畅[1] 刘丽忠 缪经纬 方翼 WU Mao-feng;TAN Xiao-ming;LIU Ran-ran;MAI Zhang-feng;LIU Chang;LIU Li-zhong;MIAO Jing-wei;FANG Yi(Phase I Clinical Research Unit,The Sixth Affiliated Hospital of Guangzhou Medical university/Qingyuan People's Hospital,Qingyuan 511518,Guangdong Province;Department of Pharmacy,Peking University People's Hospital,Beijing 100044;Qilu Pharmaceutical Co.,Ltd.,Jinan 250100,Shandong Province,China)

机构地区：[1]广州医科大学附属第六医院/清远市人民医院药物Ⅰ期临床研究室,广东清远511518 [2]北京大学人民医院药剂科,北京100044 [3]齐鲁制药有限公司,山东济南250100

出　　处：《中国临床药理学杂志》2020年第8期990-993,共4页The Chinese Journal of Clinical Pharmacology

基　　金：清远市科技计划基金资助项目(DZXQY002)。

摘　　要：目的评价3种单硝酸异山梨酯缓释片在中国健康成年人体内的药代动力学行为与相对生物利用度。方法纳入健康受试者12例,采用单中心、随机、开放、单次给药、三周期、三序列、交叉试验研究设计方法,受试者随机交叉单次口服受试制剂(T1、T2)和参比制剂(R)40 mg,用LC-MS/MS法测定单硝酸异山梨酯血药浓度,用WinNonlin 6.3软件计算药代动力学相关参数。结果受试者服用受试制剂(T1、T2)和参比制剂(R)后,血浆中单硝酸异山梨酯缓释片受试制剂(T1、T2)和参比制剂(R)Cmax分别为(548.00±66.53),(511.08±80.80),(572.92±81.70)ng·mL^-1;tmax分别为(5.75±1.73),(4.42±1.04),(4.21±0.69)h;AUC0-t分别为(7810.24±1084.02),(7535.29±1061.05),(7787.37±1263.02)ng·mL^-1·h;AUC0-∞分别为(7878.44±1078.90),(7603.18±1053.82),(7863.97±1274.41)ng·mL^-1·h;平均相对生物利用度为100.69%和97.19%。结论三种单硝酸异山梨酯缓释片具有生物等效性。Objective To evaluate the pharmacokinetic and relative bioavailability of three kinds of isosorbide mononitrate sustained release tablets in Chinese healthy subjects.Methods This was a single-center,random,open-label,single-dose,three-period,cross-over pharmacokinetic study.A total of 12 subjects in a fed state were given single oral dose of test(T1/T2)and reference(R)preparation of isosorbide mononitrate sustained release tablet(each 40 mg),respectively.The concentration of isosorbide mononitrate in human plasma was measured by LC-MS/MS.Main pharmacokinetic related parameters were calculated by using WinNonlin 6.3 software.Results The main pharmacokinetic parameters of isosorbide mononitrate of test(T1/T2)and reference(R)preparations were as follows:the Cmax were(548.00±66.53),(511.08±80.80),(572.92±81.70)ng·mL^-1;tmax were(5.75±1.73),(4.42±1.04),(4.21±0.69)h;AUC0-t were(7810.24±1084.02),(7535.29±1061.05),(7787.37±1263.02)ng·mL^-1·h;AUC0-∞were(7878.44±1078.90),(7603.18±1053.82),(7863.97±1274.41)ng·mL^-1·h.The relative bioavailability of isosorbide mononitrate were 100.69%and 97.19%.Conclusion Three kinds of isosorbide mononitrate sustained release tablets were tested to be bioequivalent.

关 键 词：单硝酸异山梨酯 相对生物利用度 药代动力学 

分 类 号：R97[医药卫生—药品]