Toxicity and Pharmacokinetics of Ciprofloxacin

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Abstract
Ciprofloxacin is a fluorinated quinolone antibiotic with a broad spectrum of activity against both gram positive and gram negative organisms. Previous studies have indicated that oral or parenteral preparations of ciprofloxacin resulted in therapeutic concentrations in the aqueous humor but intravitreal levels were found to be only marginally higher than the MIC90 for gram positive cocci. Toxicity was evaluated following intravitreal doses of ciprofloxacin injected into the mid-vitreous cavity of one eye of pigmented rabbits. As a control, an identical volume of normal saline was injected into the fellow eye. Four doses of ciprofloxacin were studied, 100 μg, 250 μg, 500 μg and 1000 μg. Electroretinograms (ERGs) were recorded prior to injection and 1, 7 and 14 days after injection. These were analyzed as b-wave amplitude ratios between treated and untreated eyes. On ophthalmoscopic examination focal areas of retinitis were observed following injection of both 500 μg and 1000 μg of ciprofloxacin but not at 250 μg. Additionally, ERG amplitude ratios were significantly reduced following the 1000 μg dose. At the 100 or 250 μg ciprofloxacin dose histological sections are comparable with control eyes and appear normal; ERG ratios were unchanged from the baseline level and careful indirect ophthalmoscopic examination revealed no alterations. Pharmacokinetic analysis after single intravitreal injection of 250 μg of ciprofloxacin (N = 3 rabbits/dose) disclosed vitreous fluid levels (μg/ml) of 146 at 0 hr, 77 at 4 hr, 32 at 8 hr, 0.49 at 24 hr and 0.24 at 48 hr. Peak aqueous humor levels of 0.59 μg/ml occurred at 8 hrs after injection and at 48 hrs, 0.09 μg/ml was detected in aqueous fluid.

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