坎地沙坦酯氨氯地平片的人体生物等效性试验  

The bioequivalence trial of candesartan cilexetil and amlodipine tablet in healthy subjects

作　　者：白万军[1] 孙雪 高瑾[2] 宋浩静[1] 胡义亭[1] 郭彩会[1] 邱博[1] 董占军[1] BAI Wan-jun;SUN Xue;GAO Jin;SONG Hao-jing;HU Yi-ting;GUO Cai-hui;QIU Bo;DONG Zhan-jun(Department of Pharmacy,Hebei General Hospital,Shjiazhuang 050051,China;Hebei General Hospital,Shjiazhuang 050051,China)

机构地区：[1]河北省人民医院药学部,石家庄050051 [2]河北省人民医院,石家庄050051

出　　处：《中国新药杂志》2022年第17期1712-1717,共6页Chinese Journal of New Drugs

基　　金：2022年政府资助临床医学优秀人才培养项目(202218);2022年度河北省医学适用技术跟踪项目(GZ2022007)。

摘　　要：目的:评价健康受试者空腹和餐后条件下单剂量服用坎地沙坦酯氨氯地平片受试制剂和参比制剂的生物等效性。方法:采用单剂量、随机、开放、两周期、自身交叉的空腹和餐后状态下的临床试验设计,应用高效液相色谱串联质谱(HPLC-MS/MS)法分别测定受试者给药后坎地沙坦和氨氯地平的血浆药物浓度,使用Phoenix WinNonlin 8.2软件计算药动学相关参数、SAS 9.4软件进行生物等效性评价。结果:空腹生物等效性试验结果表明,32例健康受试者分别单次空腹服用坎地沙坦酯氨氯地平片8 mg/5 mg受试制剂和参比制剂后,坎地沙坦的峰浓度(C_(max)),血药浓度-时间曲线下面积(AUC_(0-t)和AUC_(0-∞))的几何均值比值分别为98.93%,100.78%和100.65%,90%置信区间(CI)分别为91.09%~107.45%,95.85%~105.96%和95.78%~105.76%;氨氯地平的C_(max),AUC_(0-t)及AUC_(0-∞)的几何均值比值分别为97.89%,98.60%和98.37%,90%CI分别为92.76%~103.29%,94.98%~102.36%和94.28%~102.64%,均落在等效区间80.00%~125.00%之间。餐后生物等效性试验结果表明,32例健康受试者分别高脂餐后服用受试制剂和参比制剂,坎地沙坦的C_(max),AUC_(0-t)及AUC_(0-∞)的几何均值比值分别为98.75%,104.00%和104.02%,90%CI分别为90.79%~107.41%,99.40%~108.81%和99.48%~108.77%,氨氯地平的C_(max),AUC_(0-t)及AUC_(0-∞)的几何均值比值分别为98.90%,98.75%和98.93%,90%CI分别为93.51%~104.59%,94.65%~103.03%和94.00%~104.12%,均落在等效区间80.00%~125.00%之间。结论:在空腹和餐后条件下,坎地沙坦酯氨氯地平片受试制剂和参比制剂具有生物等效性。Objective:To evaluate the bioequivalence of preparations and reference subjects in a single dose of candesartan cilexetil and amlodipine tablet under fasting and fed conditions in healthy subjects.Methods:A single-dose,random,open-label,double-period crossover test was designed.LC-MS/MS was applied to determine the concentration of candesartan and amlodipine in plasma of healthy subjects after fasting or fed administration,and Phoenix WinNonlin 8.2 and SAS 9.4 software were used for pharmacokinetics(PK)parameter calculation and bioequivalence analysis,respectively.Results:A total of 32 healthy subjects were given the test preparation and the reference preparations candesartan cilexetil and amlodipine tablet 8 mg/5 mg under fasting condition.The ratio of the geometric mean of C_(max),AUC_(0-I) and AUC_(0-∞)of candesartan were 98.93%,100.78%and 100.65%,respectively.The 90%confidence intervals of C_(max),AUC_(0-t) and AUC_(0-∞)of Candesartan were 91.09%~107.45%,95.85%~105.96%and 95.78%~105.76%,respectively.The ratio of the geometric mean of C_(max),AUC_(0-t) and AUC_(0-∞)of amlodipine were 97.89%,98.60%and 98.37%.The 90%confidence intervals of C_(max),AUC_(0-t) and AUC_(0-∞)of amlodipine were 92.76%~103.29%,94.98%~102.36%,and 94.28%~102.64%,respectively.All these data were within the equivalent interval of 80.00%~125.00%.32 healthy subjects were given the test and reference preparations under fed condition.The ratio of the geometric mean of C_(max),AUC_(0-t) and AUC_(0-∞)of candesartan were 98.75%,104.00%and 104.02%,respectively.The 90%confidence intervals of C_(max),AUC_(0-t) and AUC_(0-∞)of candesartan were 90.79%~107.41%,99.40%~108.81%and 99.48%~108.77%,respectively.The ratio of the geometric mean of C_(max),AUC_(0-t) and AUC_(0-∞)of amlodipine were 98.90%,98.75%and 98.93%.The 90%confidence intervals of C_(max),AUC_(0-t) and AUC_(0-∞)of amlodipine were 93.51%~104.59%,94.65%~103.03%and 94.00%~104.12%,respectively,All of which were within the equivalent range of 80.00%~125.00%.Conclusion:The two for

关 键 词：坎地沙坦 氨氯地平 生物等效性试验 药动学 

分 类 号：R971.4[医药卫生—药品] R969.4[医药卫生—药学]