肠溶微丸雷贝拉唑钠胶囊的人体生物利用度及生物等效性评价

摘要

目的：：评价肠溶微丸雷贝拉唑钠胶囊的人体生物利用度及生物等效性。方法：32名健康男性志愿者随机交叉单剂量口服肠溶微丸雷贝拉唑钠胶囊(受试制剂)与雷贝拉唑钠肠溶胶囊(参比制剂)各20 mg,分别在不同时间点采集血浆样本,清洗期7 d。采用LC-MS/MS法测定血浆中雷贝拉唑浓度,采用DAS 3.0软件统计分析药动学参数。结果：受试者餐后口服肠溶微丸雷贝拉唑钠胶囊与肠溶胶囊的主要药动学参数如下：T1/2分别为(2.20±0.83) h和(1.95±0.52) h ；Tmax (3.88±1.11) h和(4.64±1.50)h；Cmax分别为(401.06±170.75)ng·ml-1和(394.63±215.64)ng·ml-1；AUC0→t分别为(918.42±427.39) ng·h·ml-1和(994.49±520.73)ng·h·ml-1；AUC0→∞分别为(937.30±445.13)ng·h·ml-1和(1011.69±534.78)ng·h· ml-1。数据分析显示：两种制剂的主要药动学参数除Tmax(P0.05)。肠溶微丸雷贝拉唑钠胶囊的相对生物利用度为(99.80±7.20)%。结论：肠溶微丸雷贝拉唑钠胶囊较参比制剂分散程度高、受食物影响小、药物释放快、吸收迅速；受试制剂与参比制剂具有生物等效性。%Objective: To evaluate the bioavallability and bioequivalence of rabeprazole sodium enteric-coated pellets capsules. Methods:A randomized crossover design was performed in 32 healthy male volunteers. A single oral dose of 20 mg rabeprazole sodium enteric-coated pellets capsules ( test preparation) or enteric-coated shell capsules ( the reference capsules) was administrated under fed conditions. The wash period was 7 days. The blood samples were collected at different time points. The concentration of rabeprazole in plasma was determined by an LC-MS/MS method. The pharmacokinetic parameters were calculated by DAS 3. 0 software and the bio-equivalence was evaluated. Results:The maln pharmacokinetic parameters of the two formulations were shown as follows:T1/2 of (2. 20 ± 0. 83)h and(1. 951 ± 0. 515)h,Tmax of (3. 88 ± 1. 11)h and(4. 64 ± 1. 504)h,Cmax of (401. 06 ± 170. 75)ng·ml-1 and(394. 63 ± 215.64)ng·ml-1,AUC0→t of (918.42 ±427.39)ng·h·ml-1 and (994.49 ±520.73)ng·h·ml-1, and AUC0→∞ of(937.30 ± 445.13)ng·h·ml-1 and(1 011.69 ±534.77)ng·h·ml-1. The analysis showed that the maln pharmacokinetic parameters of the two formulations had no significant differences(P>0. 05) except for Tmax(P<0. 05). The relative bioavallability of rabeprazole sodium enteric-coated pellets capsules was (99. 80 ± 7. 20) %. Conclusion:Compared with the reference capsules, rabeprazole sodium enter-ic-coated pellets capsules show the property of higher dispersion degree, milder influence from food, more rapid release and absorption. The enteric-coated pellets capsules and the reference capsules are bioequivalence.