氯氮平漂浮胶囊制备及多剂量给药犬体内相对生物利用度

Studies on preparation of clozapine floating sustained release capsules and its relative bioavailability after multiple doses administration in dogs

目的 制备氯氮平漂浮缓释胶囊及进行多剂量给药犬体内相对生物利用度研究。方法 根据水动力学平衡系统原理 ,制备了氯氮平胃内漂浮缓释胶囊。 8只杂种犬分别多剂量交叉给药氯氮平漂浮胶囊 75mg(1粒 ) 12h一次 ;普通片 5 0mg(2片 ) 8h一次 ,共服 5d的药动学和相对生物利用度研究。采用高效液相色谱法测定氯氮平的血浆药物浓度。 3P87程序处理测定数据。结果 与普通氯氮平片比较 ,氯氮平漂浮胶囊体外漂浮性良好 ,具有很好的缓释效果。多剂量给药后漂浮胶囊相对生物利用度为 (10 3.0 4± 6 .0 4 ) % ;漂浮胶囊和普通氯氮平片的血药浓度波动指数分别为 (49.95 4 6± 5 .3187)和 (77.0 3±5 .5 5 )。结论 漂浮胶囊具有缓释效果 ,与普通片生物利用度相当 ,在服药次数减少的情况下 ,血药浓度波动小于普通片。

OBJECTIVE: To prepare the clozapine floating sustained-release capsules (FSRC) and study its relative bioavailability in dogs. METHODS: FRSC was prepared basing on the principle of Hydrodynamically Balanced Systems. The pharmacokinetics and relative bioavailability of FRSC(75 mg, q 12 h × 5 d) of clozapine were investigated with conventional tablet(CT, 50 mg, q 8 h ± 5 d) as the reference after multiple oral administration in 8 hybrid male dogs, using an open, randomized, two-way crossover design. The plasma clozapine concentrations were determined by HPLC. RESULTS: The floating capability of FSRC in vitro was good and the sustained release property was satisfied. The relative bioavailability was (103.04 ± 6.04)%. The fluctuation index of FSRC and CT were(49.954 6 ± 5. 318 7) and (77.03 ± 5.55), respectively. CONCLUSION: FRSC had good sustained release effect and the fluctuation was lower when the dosing interval longer than CT.