Corneal pharmacokinetics of topically applied azithromycin and clarithromycin

To determine corneal levels of topically administered azithromycin and clarithromycin in a rabbit model.

Experimental animal study.

Corneas of New Zealand albino rabbits were treated with topical azithromycin (2 mg/ml or 4 mg/ml) or clarithromycin (10 mg/ml). Topical azithromycin was prepared from an intravenous solution and topical clarithromycin from a suspension for oral use. All rabbits received one drop every 2 hours on the right eye. Groups of rabbits were treated for the following intervals: 6, 12, 24, and 48 hours (four rabbits for each combination of time point, drug, and dose). Corneal tissue was removed 1 hour after the last application. To investigate stability of tissue azithromycin levels, an additional group of four rabbits was treated for 24 hours, but corneal tissue was not removed until 24 hours later. Samples were homogenized, and drug concentrations were measured using high-pressure liquid chromatography (HPLC) analysis and bioactivity assay.

Corneal concentrations of azithromycin increased with drug dosage and duration of application. Rabbits treated with azithromycin tolerated the drug well without signs of irritation. Clarithromycin was undetectable in corneal tissue by HPLC and bioactivity assay for all rabbits. Some rabbits treated with clarithromycin had signs of ocular surface irritation.

Measurable concentrations of azithromycin are achieved in corneal tissue after topical application in a rabbit model, and the drug is well tolerated. Azithromycin may be a useful antibiotic for the topical treatment of human corneal infections, but clarithromycin, in currently available formulations, may not be effective because of poor tissue penetration.