复方加替沙星滴眼液兔眼内组织分布及其药动学研究

Distribution of compound gatifloxacin eye drops in ocular tissues and its pharmacokinetics in rabbits

目的：探讨复方加替沙星滴眼液滴兔眼后加替沙星在眼内的组织分布及其药动学特征。方法：24只新西兰家兔局部滴入复方加替沙星滴眼液50μL,以高效液相色谱法测定眼内各组织中的药物浓度,用DAS 1.0软件计算药动学参数。结果：给药后5-360 min,加替沙星在泪液、房水和角膜中的最高浓度分别为（2.35±1.36）mg.g^-1,（0.307±0.056）mg.L^-1和（3.18±1.39）mg.g^-1,消除半衰期t1/2分别为（0.47±0.14）,（1.90±0.44）和（2.33±0.58）h,药时曲线下面积AUC0-6h分别为（0.43±0.11）mg.h.g^-1,（0.70±0.22）mg.h.L^-1和（7.40±2.07）mg.h.g^-1。不同时间点在晶状体、玻璃体和视网膜中均未检测到加替沙星。结论：复方加替沙星滴眼液滴眼后加替沙星前房穿透性良好,浓度较高,为其局部应用后治疗眼前段疾病提供了实验依据。

Objective： To study distribution and pharmaeokinetics of gatifloxaein in ocular tissues of rabbit after ocular instillation. Methods： Twenty four New England rabbits＇ eyes were topically applied 50 μL of compound gatifloxacin eye drops. Ocular tissues were sampled at different intervals after drug instillation, and the drug levels were assayed by HPLC. The pharmacokinetic parameters were figured Out by DAS 1.0 process. Results： The peak concentrations of gatifloxacin in tears, aqueous humors and corneas were （2.35 ± 1.36） mg.g^-1 （0. 307 ± 0.056） mg.L^-1 （3.18 ±1.39） mg.g^-1 respectively. The half-lives of elimination were （0.47 ±0.14）, （1.90 ± 0.44）, （2.33 ±0.58） h respectively. The AUC0-6h were （0.43 ±0.11） mg.h.g^-1, （0.70 ±0.22） mg.h.L^-1, （7.40 ± 2.07） mg.h.g^-1. Gatifloxacin couldn＇t be detected in retinas, lens and vitreous body. Conclusions ： Gat- ifloxacin has a good permeability and high concentration in ocular anterior segment tissues after instilling compound gatifloxacin eye drops, which provide experiment base for ocular anterior segment diseases.