两种单硝酸异山梨酯缓释片在中国健康人体内的生物等效性研究  

Bioequivalence study of two isosorbide mononitrate sustained-release tablets in Chinese healthy volunteers

作　　者：李琴 何艳 陈璐 曾艳 刘琳 张倩 李娜 周岩 刘诗静 杜鹏 曾忱 熊芸 LI Qin;HE Yan;CHEN Lu;ZENG Yan;LIU Lin;ZHANG Qian;LI Na;ZHOU Yan;LIU Shi-jing;DU Peng;ZENG Chen;XIONG Yun(Office of Drug Clinical Trial Institutions,Affiliated Hospital of Guizhou Medical University,Guizhou Guiyang 550002,China;Key Laboratory for Basic Pharmacology of Ministry of Education,Zunyi Medical University,Guizhou Zunyi 563006,China)

机构地区：[1]贵州医科大学附属医院药物临床试验机构办公室,贵州贵阳550002 [2]遵义医科大学基础药理教育部重点实验室,贵州遵义563006

出　　处：《中国医院药学杂志》2022年第19期2008-2013,共6页Chinese Journal of Hospital Pharmacy

基　　金：基础药理教育部重点实验室资助项目(编号:黔教合KY字[2022]395号)。

摘　　要：目的:研究2种单硝酸异山梨酯缓释片在中国健康人体内的药物动力学特征和生物等效性。方法:采用单次给药、随机、开放、两周期、双交叉的试验设计,健康受试者分别在空腹和餐后条件下口服单硝酸异山梨酯缓释片受试制剂与参比制剂各40 mg,利用高效液相色谱-质谱法测定血浆中药物浓度,计算相关药动学参数并评价其生物等效性。结果:(1)空腹试验中受试制剂与参比制剂的C_(max)分别为(546.52±102.32),(521.71±85.80)ng·mL^(-1),AUC_(0-t)分别为(7398.89±1298.56),(7278.29±1173.38)ng·h·mL^(-1),AUC_(0-∞)分别为(7488.82±1311.38),(7372.49±1172.09)ng·h·mL^(-1)。(2)餐后试验中受试制剂与参比制剂的C_(max)分别为(529.41±82.52),(502.21±65.15)ng·mL^(-1),AUC_(0-t)分别为(7305.10±1320.74),(7066.12±1136.99)ng·h·mL^(-1),AUC_(0-∞)分别为(7393.21±1317.32),(7160.22±1140.11)ng·h·mL^(-1)。(3)空腹和餐后试验中受试制剂与参比制剂C_(max)、AUC_(0-t)和AUC_(0-∞)几何均数的90%CI均在80.00%~125.00%范围内,表明2种制剂具有生物等效性。结论:单硝酸异山梨酯缓释片受试制剂与参比制剂在中国健康志愿者中具有生物等效性。OBJECTIVE To investigate the bioequivalence and pharmacokinetic characteristics of two kinds of isosorbide mononitrate sustained-release tablets in Chinese healthy volunteers.METHODS A randomized,crossover,two periods,and one dose clinical trial was performed in this study.The healthy volunteers were given 40 mg isosorbide mononitrate sustained-release tablets of test(T)and reference(R)preparations respectively under fasting condition and fed condition.The plasma concentration of isosorbide mononitrate was determined by HPLC-MS/MS.Pharmacokinetic parameters of isosorbide mononitrate were calculated and the bioequivalence was evaluated.RESULTS In fasting test,the pharmacokinetic parameters of T and R preparations were as follows:C_(max) were(546.52±102.32)and(521.71±85.80)ng·mL^(-1).AUC_(0-t)were(7398.89±1298.56)and(7278.29±1173.38)ng·h·mL^(-1),AUC_(0-∞)were(7488.82±1311.38)and(7372.49±1172.09)ng·h·mL^(-1),respectively.In fed test,the pharmacokinetic parameters of T and R preparations were as follows:C_(max) were(529.41±82.52)and(502.21±65.15)ng·mL^(-1),AUC_(0-t)were(7305.10±1320.74)and(7066.12±1136.99)ng·h·mL^(-1),AUC_(0-∞)were(7393.21±1317.32)and(7160.22±1140.11)ng·h·mL^(-1),respectively.In fasting and fed tests,the 90%CI of the geometric mean ratios of C_(max),AUC_(0-t)and AUC_(0-∞)between T and R preparations were all within the range of 80.00%-125.00%,suggesting the two preparations were bioequivalent.CONCLUSION The two kinds of isosorbide mononitrate sustained-release tablets are bioequivalent in Chinese healthy volunteers.

关 键 词：单硝酸异山梨酯缓释片 生物等效性 高效液相色谱-质谱法 

分 类 号：R969[医药卫生—药理学]