Comparative Ocular Bioavailability and Efficacy of Topical Levofloxacin and Ofloxacin in Rabbits

Abstract

Levofloxacin and ofloxacin are fluoroquinolone antibacterial agents with activity against a broad spectrum of Gram‐positive and Gram‐negative ocular pathogens. Levofloxacin is the pure S‐(−) isomer of ofloxacin, and is approximately twice as active as the R‐(+) isomer. Studies were conducted to measure the pharmacokinetics of levofloxacin and ofloxacin in the cornea and aqueous humor of the intact rabbit eye and also to determine the therapeutic efficacy of the two compounds for the treatment of experimental pseudomonas keratitis. A single ocular dose of 1.5% levofloxacin to intact rabbit eyes produced average maximum concentration (Cmax) values in both cornea and aqueous humor that were approximately five times greater than that of 0.3% ofloxacin. Furthermore, concentrations of levofloxacin in corneas were maintained above the minimum inhibitory concentration 90% (MIC90) for most ocular pathogens for more than 2 hours following a single topical dose. In a rabbit model of pseudomonas keratitis, dosing rabbits for 2 days with either 1.5% levofloxacin every 2 hours, or 0.3% ofloxacin every 30 minutes, resulted in the elimination of viable pseudomonas organisms from all treated rabbits. The results of these bioavailability and efficacy studies support the concept that a less frequent dosing regimen with 1.5% levofloxacin ophthalmic solution (every 2 hours) will be as effective as dosing 0.3% ofloxacin every 30 minutes for treatment of bacterial keratitis.