Corneal pharmacokinetics of topical clarithromycin.
OBJECTIVE
To evaluate the pharmacokinetics of topically applied clarithromycin, a new macrolide antibiotic, at various concentrations in a rabbit model.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Gross
R H
RH
UCLA Ocular Inflammatory Disease Center, University of California at Los Angeles School of Medicine 90024-7003, USA.
Holland
G N
GN
Elias
S J
SJ
Tuz
R
R
D000042:Absorption; D000287:Administration, Topical; D000818:Animals; D001682:Biological Availability; D017291:Clarithromycin / Q000493:pharmacokinetics*; D003315:Cornea / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D009883:Ophthalmic Solutions; D011817:Rabbits; D011897:Random Allocation
D009883:Ophthalmic Solutions; D017291:Clarithromycin