加替沙星眼用凝胶药动学研究

Pharmacokinetics of Gatifloxacin Ophthalmic Gel in Ocular Delivery

目的研究加替沙星眼用凝胶单次滴眼后加替沙星的药动学特征并与加替沙星滴眼液进行比较。方法采用新西兰家兔,左眼滴入加替沙星眼用凝胶60μL,右眼滴入加替沙星滴眼液60μL,分别于不同时间取泪液、房水和角膜,采用液-质联用（LC-MS）的方法对其中的药物含量进行测定。结果实验组和对照组单次给药后,泪液中药物消除半衰期分别为195.3和80.7 min,AUC0-480分别为62 385和33 280μg·min·g^-1;房水中实验组与对照组的药物达峰浓度分别为1.05和0.62mg·L^-1,达峰时间均为60 min,AUC0-360分别为111.7和66.1 mg·min·L^-1;角膜中实验组与对照组的AUC0-480分别为3 435.5和1 688.4μg·min·g^-1。结论实验药与对照药的药动学参数具有显著差异,加替沙星眼用凝胶用药后药物在泪液、房水和角膜中具有较高的药物浓度且能维持较长的时间,较加替沙星滴眼液生物利用度显著提高。

OBJECTIVE To compare the pharmacokinetics and bioavailability of gatifloxacin ophthalmic gel with gatifloxacin eye drops by topical application.METHODS New Zealand rabbits＇ left eyes were topically applied 60 μL of gatifloxacin ophthalmic gel,the right eyes were topically applied 60 μL of gatifloxacin eye drops.Tears,aqueous humors and corneas were sampled at different intervals after drug instillation,and the drug levels were assayed by liquid chromatograph/mass spectrometer（LC-MS）.RESULTS The half-lives of elimination in the tears were 195.3 and 80.7 min,and the AUC0～480 of the drug levels in the tears were 62 385 and 33 280 μg·min·g^-1 for the test group and the reference group respectively.The peak levels of drug in aqueous humors were 1.05 and 0.62 mg·L^-1,and the AUC0～360 of the drug levels in the aqueous humors were 111.7 and 66.1 mg·min·L^-1 respectively.The AUC0～480 of the drug levels in the corneas were 3 435.5 and 1 688.4 μg·min·g^-1 respectively.CONCLUSION The bioavailability of gatifloxacin ophthalmic gel was increased significantly,and its action time was obviously increased compared with gatifloxacin eye drops.