RETINAL SAFETY OF ORAL AND TOPICAL OFLOXACIN IN RABBITS

Ofloxacin is a broad spectrum fluoroquinolone antibiotic with good ocu lar penetration. We investigated the potential for retinal toxicity as sociated with increased intraocular penetration following intensive to pical, oral, and combined topical and oral administration. We confirme d ofloxacin concentrations in aqueous and vitreous following these for ms of administration. Rabbits received either topical, oral, or a comb ination of oral and topical ofloxacin. Topical administration consiste d of one drop of ofloxacin 0.3% drops given every thirty minutes for a total of eight doses. Oral ofloxacin was administered at a dose of 10 mg (4 mg/kg for average weight 2.5 kg rabbit) every 12 hours for a to tal of three doses. Six rabbits were followed longitudinally for 4 wee ks for evidence of retinal toxicity by indirect ophthalmoscopy and ser ial ERGs. Electron and light microscopic histopathologic examination o f the retina were performed 4 weeks following drug administration. To verify intraocular penetration, ten rabbits received identical dosing schedules followed by HPLC measurement of aqueous and vitreous drug co ncentrations at 1, 4, 8, 12, and 24 hours following dose completion. N o evidence of retinal toxicity was detected by indirect ophthalmoscopy , electroretinography, or histopathological examination. Vitreous oflo xacin levels were highest after combined oral and topical administrati on, peaking at 0.892 mu g/ml 8 hours following dosage completion. The peak vitreous level following oral administration was 0.230 mu g/ml an d 0.026 mu g/ml following topical administration. Peak aqueous humor l evels were achieved one hour following drug administration and were 11 .400 mu g/ml after topical, 0.206 mu g/ml after oral, and 8.180 mu g/m l after combined administration. Our study suggests that intensive top ical and oral ofloxacin administration does not cause retinal toxicity in rabbits, despite achieving effective aqueous and vitreous humor an timicrobial concentrations.