单硝酸异山梨酯缓释胶囊人体生物等效性研究  

Bioequivalence of Isosorbide Mononitrate Sustained Release Capsules in Chinese Healthy Volunteers

作　　者：王永超 谢斌 王东凯[1] WANG Yongchao;XIE Bin;WANG Dongkai(School of Pharmacy,Shenyang Pharmaceutical University Shenyang 110016,China;Zhuhai Rundu Pharmaceutical Co.Ltd.,Zhuhai 519041,China)

机构地区：[1]沈阳药科大学药学院,沈阳110016 [2]珠海润都制药股份有限公司,珠海519041

出　　处：《医药导报》2021年第4期533-537,共5页Herald of Medicine

摘　　要：目的评价2种单硝酸异山梨酯缓释胶囊(50 mg)在中国健康受试者中的生物等效性。方法本次研究共56例受试者入组(空腹和餐后各28例),采用单剂量、随机、开放、双周期交叉设计。用高效液相色谱-串联质谱法测定单硝酸异山梨酯的血药浓度。Phoenix WinNonlin 8.1计算药动学参数,将峰浓度(C_(max))、血药浓度-时间曲线下面积(AUC_(0-t))、AUC_(0-∞)经对数转换后进行方差分析,计算几何均值的90%置信区间。结果空腹单次口服单硝酸异山梨酯缓释胶囊受试制剂和参比制剂后的主要药动参数如下:C_(max)分别为(510.79±86.26)和(497.96±87.50)ng·mL^(-1);AUC_(0-t)分别为(7899.04±1240.31)和(7823.72±1328.23)h·ng·mL^(-1);AUC_(0-∞)分别为(8054.56±1270.10)和(7968.81±1351.22)h·ng·mL^(-1);峰时间(t_(max))分别为(6.61±0.95)和(6.52±1.73)h,半衰期(t_(1/2))分别为(5.66±0.53)和(5.62±0.43)h。餐后单次口服单硝酸异山梨酯缓释胶囊受试制剂和参比制剂后的主要药动学参数如下:C_(max)分别为(508.46±149.25)和(555.32±94.05)ng·mL^(-1);AUC_(0-t)分别为(7094.47±1543.14)和(7471.03±1188.86)h·ng·mL^(-1);AUC_(0-∞)分别为(7249.53±1594.16)和(7625.27±1242.10)h·ng·mL^(-1);t_(max)分别为(6.94±1.15)和(7.02±1.25)h,t_(1/2)分别为(5.66±0.66)和(5.63±0.60)h。空腹试验C_(max)、AUC_(0-t)、AUC_(0-∞)几何均数比值的90%置信区间分别为(99.91~105.55)%,(98.85~103.54)%,(98.89~103.70)%;餐后试验C_(max)、AUC_(0-t)、AUC_(0-∞)几何均数比值的90%置信区间分别为(88.54~97.23)%,(95.21~99.48)%,(95.12~99.55)%。结论空腹和餐后条件下单次口服受试制剂和参比制剂均具有生物等效。Objective To evaluate the bioequivalence(BE)of two types of isosorbide mononitrate sustained release capsules(50 mg)in Chinese healthy volunteers.Methods A total of 56 healthy subjects(28 each in the fasting and post-prandial groups)were enrolled in the study,using a single-dose,randomized,open-label,two-period crossover design for the treatment.The plasma concentrations of isosorbide mononitrate were measured by LC-MS/MS.The pharmacokinetic parameters were calculated,and the 90%confidence intervals(CI)of the geometric mean ratio(test/reference)of the parameters were obtained by the analysis of variance on logarithmically transformed data with WinNolin 8.1.Results The main pharmacokinetics parameters of the test and reference administered fasted subjects were as follows:C_(max)were(508.46±149.25)and(555.32±94.05)ng·mL^(-1);AUC_(0-t)were(7094.47±1543.14)and(7471.03±1188.86)h·ng·mL^(-1);AUC_(0-∞)were(7249.53±1594.16)and(7625.27±1242.10)h·ng·mL^(-1);t_(max)were(6.94±1.15)and(7.02±1.25)h;t_(1/2)were(5.66±0.66)and(5.63±0.60)h.Under fasting conditions,the 90%confidence intervals of C_(max),AUC_(0-t)and AUC_(0-∞)for the test/reference geometric mean ratio were(99.91~105.55)%,(98.85~103.54)%,and(98.89~103.70)%;Under fed conditions,the 90%confidence intervals of C_(max),AUC_(0-t)and AUC_(0-∞)for the test/reference geometric mean ratio were(88.54~97.23)%,(95.21~99.48)%,(95.12~99.55)%.Conclusion The test product was equivalent to the reference product in subjects under fasting and post-prandial conditions.

关 键 词：单硝酸异山梨酯缓释胶囊 生物等效性 药动学 空腹 餐后 高效液相色谱-串联质谱法 

分 类 号：R972.1[医药卫生—药品] R969.1[医药卫生—药学]