Toxicity of Moxifloxacin Ophthalmic Solution 0.5% in the Rabbit

Abstract

Abstract: : Purpose: To determine the ocular irritation and systemic toxicity potential of Moxifloxacin ophthalmic solutions in repeated-dose topical ocular studies in the rabbit. Methods: Two studies involving repeated-dose topical ocular administration to rabbits were used to evaluate the ocular and systemic toxicity potential. The first study was a 4 week study in New Zealand White rabbits. The second rabbit study was performed in an F1-cross (New Zealand White x New Zealand Red) pigmented rabbit for one month. All rabbits were dosed with drops of 0.5%, 1.0% or 3.0% moxifloxacin solution or vehicle four times daily (QID). Results: Moxifloxacin treated rabbits revealed no significant treatment-related clinical signs or body weight changes during the treatment periods. Indirect ophthalmoscopic evaluations determined that all animals were within normal limits. Statistical analyses of pachymetry measurements revealed no significant findings. No gross lesions in ocular tissues were observed during necropsy. Slit-lamp biomicroscopic examinations revealed only minimal to moderate conjunctival congestion (hyperemia) across all treatment and control groups. Histopathological evaluation of the eyes and adnexa revealed no treatment related changes or evidence of ocular irritation. In both studies, topical application yielded less than 1 µg/mL of moxifloxacin in plasma. Conclusions: These toxicity studies in rabbits demonstrate that there is a substantial margin of safety for topically administered moxifloxacin solutions between 0.5% and 3.0%. Based on these results, 0.5% to 3.0% moxifloxacin solutions were non-toxic and exhibited low ocular irritation potential and did not elicit any signs of ocular or systemic toxicity.

Keywords: ocular irritancy/toxicity testing • antibiotics/antifungals/antiparasitics • animal model