氟康唑原位胶化滴眼液眼内药代动力学研究  

PHARMACOKINETICS OF TOPICALLY APPLIED IN-SITU-FORMING GELS OF FLUCONAZOLE IN RABBIT EYES

作　　者：张俊杰[1] 谢雷克[1] 赵宁民 陈祖基[1] 徐岩[1] 

机构地区：[1]河南省眼科研究所,河南郑州450003

出　　处：《药学学报》2000年第11期835-838,共4页Acta Pharmaceutica Sinica

基　　金：河南省卫生厅资助课题 !(980 0 7)

摘　　要：目的　比较氟康唑滴眼液及其原位胶化滴眼液在兔眼内药代动力学。方法　两种制剂滴眼后 ,用气相色谱法测定不同时间的兔眼结膜囊内泪液和房水中氟康唑浓度 ,药动学参数用非线性最小二乘法进行计算机拟合求得。结果　用药后 180min内 ,原位胶化组各时间点结膜囊内泪液药物浓度均明显高于一般滴眼液组。原位胶化组的房水药物浓度 时间曲线下面积和消除半衰期明显高于对照组 ,达峰时间延迟 ,但达峰浓度与一般滴眼液组无明显差异。结论　氟康唑原位胶化滴眼液可明显延长药物在眼部的滞留时间 。AIM To study the pharmcokinetics of fluconazole (FCZ) in the aqueous humors and tears of New Zealand white rabbits following topically applied in situ forming gels of 0 5% FCZ (ISG FCZ) and 0 5% FCZ eye drops to rabbit eyes. METHODS The rabbit tears and aqueous humors were obtained and quantified at different times after topically applying single dose of ISG FCZ and FCZ eye drops to the rabbit eyes. The drug levels were assayed by megabore capillary gas liquid chromatography with nitrogen selective detector. The pharmacokinetic parameters were calculated with nonlinear least square methodwithcomputer.RESULTS FCZ concentrations in rabbit tears within 180 min after applying ISG FCZ were found to be significantly higher compared with those of FCZ eye drops. The FCZ levels in the aqueous at 10, 30, 60, 90 and 120 min after applying ISG FCZ are significantly higher compared with FCZ eye drops. The time for arriving peak concentration ( T max ) and the area under concentration (AUC) time curve as well as the half life ( T 1/2 ) of FCZ in rabbit aqueous humors were markedly higher after application of ISG FCZ. The peak levels in the aqueous humors showed no difference between the two groups. CONCLUSION The ISG FCZ, which upon exposure to physiological conditions will shift the gel phase, can significantly extend FCZ release and increase the precorneal residence time of the drug, thus enhance ocular bioavailability compared with FCZ eye drops.

关 键 词：氟康唑 原位胶化 药代动力学 滴眼液 

分 类 号：R988.1[医药卫生—药品] R969.1[医药卫生—药学]