摘要
目的评估布洛芬缓释胶囊(300 mg)受试制剂和参比制剂在中国健康受试者中生物等效性。方法采用随机、开放、单中心、单剂量、两制剂、两周期、两序列、自身交叉的生物等效性试验设计。空腹和餐后各入组健康受试者24例,每周期单次给予受试制剂或参比制剂300 mg,清洗期7 d。高效液相色谱-串联质谱(HPLC-MS/MS)法测定人血浆中布洛芬的浓度,并评估两种制剂的生物等效性。结果空腹口服受试制剂和参比制剂后,布洛芬主要药动学参数如下:峰浓度(C max)分别为(13603.75±3606.48)和(14051.25±2876.49)ng·mL-1;血药浓度-时间曲线下面积(AUC 0-t)分别为(98846.34±22299.01)和(99836.30±19621.61)h·ng·mL-1;AUC 0-∞分别为(103207.00±23890.57)和(103524.09±22292.75)h·ng·mL-1;峰时间(t max)分别为4.5和4.5 h;消除半衰期(t 1/2)分别为(4.32±1.92)和(4.10±1.23)h。餐后口服受试制剂和参比制剂后,其主要药动学参数如下:C max分别为(20552.17±5320.53)和(19170.83±2945.22)ng·mL-1;AUC 0-t分别为(102412.31±19314.50)和(101928.24±21749.75)h·ng·mL-1;AUC 0-∞分别为(102979.26±19583.29)和(102549.36±22126.08)h·ng·mL-1;t max分别为4.5和4.5 h;t 1/2分别为(2.97±0.34)和(2.92±0.36)h。空腹试验中受试制剂与参比制剂C max、AUC 0-t、AUC 0-∞几何均数比值的90%置信区间分别为(89.86%,102.08%),(94.05%,103.40%),(94.35%,104.72%)。餐后试验中受试制剂与参比制剂C max、AUC 0-t、AUC 0-∞几何均数比值的90%置信区间分别为(97.43%,112.29%),(95.44%,103.59%),(95.32%,103.62%)。结论空腹和餐后条件下单次口服布洛芬缓释胶囊受试制剂和参比制剂具有生物等效。
Objective To evaluate the bioequivalence of ibuprofen sustained release capsules(300mg)in Chinese healthy subjects.Methods A randomized,open-label,single-center,single-dose,two-preparation,two-period,two-sequence,and self-crossover bioequivalence trial was performed in Chinese healthy volunteers.Both fasting and fed trials enrolled 24 healthy subjects.A single dose of test or reference ibuprofen sustained release capsules(300 mg)was administered under fasting or fed conditions per period with 7-day washout period.The concentration of ibuprofen in plasma was determined by HPLC-MS/MS,which was used to evalute the bioequivalence of the two preparations.Results The main pharmacokinetic parameters under fasting conditions for the test and the reference sustained release capsules were as follows:C max were(13603.75±3606.48)vs.(14051.25±2876.49)ng·mL-1;AUC 0-t were(98846.34±22299.01)vs.(99836.30±19621.61)h·ng·mL-1;AUC 0-∞were(103207.00±23890.57)vs.(103524.09±22292.75)h·ng·mL-1;t max were 4.5 vs.4.5 h;t 1/2 were(4.32±1.92)vs.(4.10±1.23)h.The main pharmacokinetic parameters under fed conditions for the test and the reference sustained release capsules were as follows:C max were(20552.17±5320.53)vs.(19170.83±2945.22)ng·mL-1;AUC 0-t were(102412.31±19314.50)vs.(101928.24±21749.75)h·ng·mL-1;AUC 0-∞were(102979.26±19583.29)vs.(102549.36±22126.08)h·ng·mL-1;t max were 4.5 vs.4.5 h;t 1/2 were(2.97±0.34)vs.(2.92±0.36)h.Under fasting conditions,the 90%confidence intervals of C max,AUC 0-t and AUC 0-∞geometric mean ratios were(89.86%,102.08%),(94.05%,103.40%)and(94.35%,104.72%).Under fed conditions,the 90%confidence intervals of C max,AUC 0-t and AUC 0-∞geometric mean ratios were(97.43%,112.29%),(95.44%,103.59%)and(95.32%,103.62%).Conclusion It could therefore be concluded that the test preparation of ibuprofen sustained release capsules was bioequivalent to that of reference.
作者
陈新民
刘杰
谢斌
杨沛欣
杨琼
CHEN Xinmin;LIU Jie;XIE Bin;YANG Peixin;YANG Qiong(Zhuhai Rundu Pharmaceutical Co.Ltd.Zhuhai,519041,China)
出处
《医药导报》
CAS
北大核心
2021年第10期1412-1417,共6页
Herald of Medicine
基金
广东省省级科技计划项目(2017B020234003)。
