格尔德霉素滴眼液兔眼角膜吸收的研究

The absorption of geldanamycin in eye drops by cornea of rabbits

目的:制备格尔德霉素滴眼液,进行兔眼角膜吸收实验,检测角膜及房水中药物量。方法:以健康新西兰大白兔为实验对象,单剂量给药,在不同时间点取房水及角膜,用HPLC法分别测定药物在角膜及房水中药物吸收量,用3p87药动学程序进行房室模型模拟和参数拟合。并进行体内外相关性考察。结果:药物易被角膜吸收,但不易渗透进入房水,药物在体角膜吸收符合血管外给药一级吸收一室模型。药物在眼部滞留时间较长,平均滞留时间为3.07h,有一定的缓释怍用,利于提高药物生物利用度。体内外实验具较好的相关性(r=0.9086)。结论:格尔德霉素滴眼液易被兔眼角膜吸收,且在角膜中达到较高浓度,在治疗单纯疱疹性病毒性角膜炎方面具有良好的前景。

Objective: To prepare geldanamycin eye drops, to study the absorption of geldanamycin in eye drops by cornea of rabbits and determine its content in cornea and aqueous humor. Methods:The eye drops were administered to health rabbits and samples of cornea and aqueous humor were taken as time schedule after a single dose. Geldanamycin level in samples was determined respectively by HPLC method and 3p87 processor was adopted to simulate compartment model and parameters. The correlation of in vitro and in vivo absorption was evaluated. Results:Geldanamycin was easily absorbed by cornea but hardly permeated into aqueous humor. Absorption of geldanamycin in cornea fitted to a model of one department and one order absorption. Time detained in cornea for geldanamycin was rather long about 3.07h and the delay was favorable to its bioavailability. The relationship between in vitro and in vivo experiment was correlated (r = 0.9086). Conclusion: In rabbits, geldanamycin in eye drops is easily absorbed by cornea and maintained a higher level in it. Therefore, there is a favorable prospect for geldanamycin eye drops in treatment of herpes simplex keratitis.