摘要
目的:考察眼用复方阿奇霉素温度敏感型原位凝胶兔眼局部单次应用后角膜及房水中的药动学特征.方法:日本大耳白兔39只,随机分为13个时间组,双眼分别给予眼用复方阿奇霉素温度敏感型原位凝胶50μl,分别于给药后5,15,30 min,1,6,12,24,48,96,144,192,240h后抽取房水,处死,剖取角膜组织,以HPLC-MS/MS法检测角膜及房水中的药物浓度,评价阿奇霉素在兔眼角膜及房水中药动学特征.结果:房水中的达峰浓度(Cmax)为(0.050 1±0.015) μg·m1-1(1 h),角膜中的达峰浓度为(45.2±14.3) μg·g-1(15min);房水中和角膜中阿奇霉素的半衰期(t1/2)分别为85.0 h和84.4 h;房水中和角膜中的AUC(0-240)分别为1.230 7 μg·ml-1·h-1和1 969.8μg·g 1·h-1.结论:眼用复方阿奇霉素温度敏感型原位凝胶兔眼给药后,角膜中迅速的达到较高的药物浓度,并持续较长时间,有很好的临床应用前景.
Abstract
OBJECTIVE To evaluate the cornea and aqueous humor pharmacokinetics of compound azithromycin in situ gel after topical application.METHODS 39 Japanese white rabbits were divided into 13 groups randomly.50 μl compound azithromycin in situ gel was instilled into the rabbit eyes of both sides.Aqueous humor were collected and the rabbits were executed after 5,15,30 min,1,6,12,24,48,96,144,192,240 h.Then the cornea was collected.The concentrations of azithromycin in cornea and aqueous humor was detected by HPLC-MS/MS.RESULTS The peak concentration (Cmax) of azithromycin in aqueous humor and cornea was (0.050 ± 0.015) μg·ml-1 (1 h)and (45.2 ± 14.3)μg·g-1 (15 min),respectively.The half-life periods (t1/2) of azithromycin in aqueous humor and cornea were 85.0 h and 84.4 h.The AUC(0-240) of azithromycin in aqueous humor and cornea was 1.230 7μg·ml-1· h-1 and 1 969.8 μg·g-1 ·h-1,respectively.CONCLUSION High drug concentrations in rabbit cornea were observed after topical instillation of ophthalmic compound azithromycin in situ gel.The relatively high drug level could be maintained at a quite long term.It has a very good prospect for clinical application.
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维普
万方数据