Tolerability, kinetics, and efficacy of subconjunctival pefloxacin in pigmented rabbits

Abstract

Pefloxacin has been shown to have good intraocular penetration when given systemically. In order to extend its clinical use, we have assessed the tolerability, kinetics, and efficacy of subconjunctival pefloxacin in phakic pigmented rabbits. The tolerability of a single subconjunctival injection of pefloxacin (0.8, 1.6, 8, or 16 mg in 0.2 ml) in the right eyes of eight rabbits was evaluated by clinical and histopathological examination. The 0.8-mg dose of pefloxacin was well tolerated. The kinetics was evaluated after a single subconjunctival injection of 0.8 mg in 18 rabbits. Animals were sacrificed at 1, 3, 5, 7, 12, or 18 h postinjection. Drug concentrations were measured by high-performance liquid chromatography. Pefloxacin was found in the cornea (maximum concentration, 18.13 micrograms/ml; half-life, 3.92 h) and in the aqueous humor (maximum concentration, 3.40 micrograms/ml; half-life, 2.14 h). Pefloxacin did not penetrate into the vitreous humor by this route. The efficacy was evaluated in an experimental model of staphylococcal corneal ulcers in eight rabbits which received two subconjunctival injections of 0.8 mg of pefloxacin at 16 and 24 h after intrastromal inoculation. The results (expressed as mean log10 CFU per milliliter +/- standard deviation) showed that pefloxacin significantly (P < 0.001) reduced the bacterial counts (4.39 +/- 0.97) compared with those in control eyes (6.46 +/- 0.69). For phakic eyes, subconjunctival pefloxacin might be of value for the treatment of corneal ulcers. Further studies are required to determine its penetration into the vitreous humor of aphakic eyes.