萘普生缓释胶囊与普通片在健康人的药物动力学和生物利用度比较

COMPARISON OF PHARMACOKINETICS AND BIOAVAILABILITY OF NAPROXEN BETWEEN SUSTAINED RELEASE CAPSULE AND CONVENTIONAL TABLET IN HEALTHY VOLUNTEERS

用肠溶性辅料将Nap制成孔道型骨架结构的缓释胶囊,与市售片进行溶出度比较;用HPLC测定健康受试者1次和多次服用本胶囊和片剂后的血药浓度,计算胶囊剂的生物利用度.结果:Nap缓释胶囊具有缓释作用,缓释胶囊1次给药后3～24h血药浓度在40～80μg/ml的有效浓度范围内,多次给药缓释胶囊能较快达到稳态,峰谷浓度波动小,与普通片生物利用度相当,具有生物等效性;体内吸收与体外溶出度有显著相关性.提示Nap能动释胶囊是一种1d眼药1次能够维持有效治疗浓度的新的缓释制剂.

OBJECTIVE: Naproxen sustained release capsule which is one of oral administered formulation for once daily was studied. METHODS: By using enteric soluble ingredients, naproxen was made into sustained release capsules. This capsule is porosity skeleton stucture. Its dissolution was compared with domestic tablets. In the bioavailability study, naproxen concentration was detected by a HPLC method after oral single and multidoses in healthy subjects. RESULTS: The dissolution rate of the capsules approached 90% at 10h and 95% at 12h. That of domestic tablets were more than 90% at 30 min. It showed that dissolution of the sustained release capsules is apparently slow than that of domestic tablets. In healthy subject study,the serum concentrations were 40-80μg/ml at 3-24 h after single administraton of capsules. The fluctuation of peak and trough concentrations was lower than that of domestic tablets with multi-doses. The bioavailability of the capsules was bioequa-lence with domestic tablets. It was good relative in relationship between bioavailability in vivo and dissolution in vitro. CONCLUSION: The sustained release capsule is new preparation maintaining effective concentration for once daily.