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目的探讨RAPA(雷帕霉素)眼膏涂眼后在兔眼房水中药物分布。方法制备载药率5.140%RAPA眼膏,给新西兰白兔双眼结膜囊涂布眼膏,给药后30、60、120、240、480、720min应用高效液相色谱法(HPLC)测定房水中RAPA药物浓度,计算反映RAPA眼膏的生物利用度的指标:最大浓度(maximal concentration,Cmax)、达峰时间(maximal time,Tmax)、曲线下面积(Area under the curve,AUC)等。结果涂眼30、60、120、240、480、720min后,RAPA房水浓度为0.5120±0.0650μg.l-1、5.024±0.307μg.l-1、20.38±1.14μg.l-1、4.723±0.352μg.l-1、3.169±0.198μg.l-1、1.335±0.161μg.l-1;RAPA眼膏房水持续释药720min,房水Cmax为20.38±1.45μg.l-1,Tmax120min。房水中释药模式亦大致呈三相,即初始突释、稳态缓释和减弱释药。稳态缓释相房水维持600min,平均释药浓度为3.169±0.19μg.l-1,随即表现为减弱至检测限以下;AUC为5711μg·min.l-1。结论我们制备的RAPA眼膏在兔眼放水中有良好的穿透性和有效的治疗浓度。RAPA眼膏完全可以用来治疗角膜移植免疫排斥和眼表免疫相关性疾病。
Objective To investigate the distribution of drug in aqueous humor of rabbits after RAPA (rapamycin) eye ointment. Methods RAPA eye ointment with 5.140% drug loading rate was prepared and applied to eyes of New Zealand white rabbits with conjunctival conjunctiva. RAPA was measured by HPLC at 30, 60, 120, 240, 480 and 720 minutes after administration. Drug concentration, calculate the indexes that reflect the bioavailability of RAPA ointment: maximal concentration (Cmax), maximal time (Tmax), area under the curve (AUC) and so on. Results After 30, 60, 120, 240, 480, and 720 min of eye coating, the RAPA aqueous humor concentration was 0.5120 ± 0.0650μg.l -1.5.024 ± 0.307μg.l-1 and 20.38 ± 1.14μg.l -1,7.723 ± 0.352μg · l-1,3.169 ± 0.198μg · l -1,1.335 ± 0.161μg.l-1; RAPA ocular aqueous humor sustained release of 720min, aqueous Cmax of 20.38 ± 1.45μg.l-1, Tmax120min. Aqueous release model is also roughly three-phase, that is, the initial burst release, steady-state release and weakened release drug. The steady-state sustained-release phase aqueous humor was maintained for 600min, the average release concentration was 3.169 ± 0.19μg.l-1, then decreased to the limit of detection; AUC was 5711μg · min-1. Conclusions The RAPA ointment we prepared has a good penetration and an effective therapeutic concentration in the drainage of rabbit eyes. RAPA eye ointment can be used to treat keratoplasty immune rejection and ocular immune-related diseases.