Gross R H, Holland G N, Elias S J, Tuz R
UCLA Ocular Inflammatory Disease Center, University of California at Los Angeles School of Medicine 90024-7003, USA.
Invest Ophthalmol Vis Sci. 1995 Apr;36(5):965-8.
To evaluate the pharmacokinetics of topically applied clarithromycin, a new macrolide antibiotic, at various concentrations in a rabbit model.
Clarithromycin in dosages of 10, 20, and 40 mg/ml was administered topically every 2 hours for 48 hours to three groups of 16 New Zealand albino rabbits. Both corneas were treated. Right corneas were deepithelialized with n-heptanol. At 6, 12, 24, and 48 hours, tissue concentrations were determined in four animals from each group.
Tissue drug concentrations increased with drug dosage and duration of therapy. Drug concentrations were significantly higher at 48 hours than at 6 hours, 12 hours, and 24 hours for both epithelialized and deepithelialized eyes in the 20 mg/ml and 40 mg/ml treatment groups (all P < or = 0.0015). A steady state concentration was not achieved in any group. Tissue drug concentrations were higher in deepithelialized corneas for each dose after 6 hours, although differences were not significant (all P > 0.059). Highest mean drug concentration at 48 hours was 241 micrograms/g in animals receiving 40 mg/ml of clarithromycin. After 6 hours, tissue concentrations in some groups were above MIC90 for many Chlamydia sp., Streptococcus sp., and Staphylococcus sp., and by 12 hours, concentrations were greater than MIC90 in all groups for many nontuberculous mycobacteria.
Topical clarithromycin achieves therapeutic levels in corneal tissue in a rabbit model. Clarithromycin might be a useful broad-spectrum antibiotic for topical use in humans.
在兔模型中评估不同浓度的新型大环内酯类抗生素局部应用后克拉霉素的药代动力学。
将10、20和40mg/ml剂量的克拉霉素每2小时局部给药一次，持续48小时，分别给予三组共16只新西兰白兔。双眼角膜均接受治疗。右眼角膜用正庚醇去除上皮。在6、12、24和48小时时，每组取4只动物测定组织浓度。
组织药物浓度随药物剂量和治疗持续时间增加。在20mg/ml和40mg/ml治疗组中，上皮化和去上皮化眼在48小时时的药物浓度显著高于6小时、12小时和24小时时的浓度（所有P≤0.0015）。任何一组均未达到稳态浓度。6小时后，各剂量组去上皮化角膜中的组织药物浓度均较高，尽管差异不显著（所有P>0.059）。接受40mg/ml克拉霉素的动物在48小时时的最高平均药物浓度为241μg/g。6小时后，一些组的组织浓度高于许多衣原体属、链球菌属和葡萄球菌属的MIC90，到12小时时，所有组中许多非结核分枝杆菌的浓度均大于MIC90。
在兔模型中，局部应用克拉霉素可在角膜组织中达到治疗水平。克拉霉素可能是一种对人类局部使用有用的广谱抗生素。
