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Toxicity and pharmacokinetics of ciprofloxacin
A L Marchese1, V S Slana, E W Holmes
1Department of Ophthalmology, Loyola University Medical Center, Maywood, Illinois.
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 micrograms, 250 micrograms, 500 micrograms and 1000 micrograms. 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 micrograms and 1000 micrograms of ciprofloxacin but not at 250 micrograms. Additionally, ERG amplitude ratios were significantly reduced following the 1000 micrograms dose. At the 100 or 250 micrograms 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 micrograms of ciprofloxacin (N = 3 rabbits/dose) disclosed vitreous fluid levels (microgram/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.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Intravitreal injections of ciprofloxacin showed potential ocular toxicity at higher doses (500 and 1000 micrograms) in rabbits, with no significant toxicity observed at 250 micrograms. This suggests a safe dose for potential intraocular infections.
Area of Science:
- Ophthalmology
- Pharmacology
- Microbiology
Background:
- Ciprofloxacin, a broad-spectrum fluoroquinolone antibiotic, achieves therapeutic levels in aqueous humor but limited intravitreal concentrations.
- Previous research suggests intravitreal ciprofloxacin levels may be only marginally above the minimum inhibitory concentration (MIC90) for Gram-positive cocci.
Purpose of the Study:
- To evaluate the ocular toxicity and pharmacokinetics of intravitreal ciprofloxacin in pigmented rabbits.
- To determine a potentially safe and effective intravitreal dosage of ciprofloxacin for ocular infections.
Main Methods:
- Intravitreal injections of varying ciprofloxacin doses (100, 250, 500, 1000 micrograms) were administered to rabbit eyes.
- Electroretinograms (ERGs) and ophthalmoscopic examinations were performed to assess retinal function and toxicity.
- Pharmacokinetic analysis was conducted after a single 250 microgram intravitreal injection.
Main Results:
- Ophthalmoscopic examination revealed focal retinitis at 500 and 1000 microgram doses.
- Significant reduction in ERG b-wave amplitude ratios was observed with the 1000 microgram dose.
- No significant histological or ERG changes were noted at 100 or 250 microgram doses, with vitreous levels remaining detectable for up to 48 hours post-injection at 250 micrograms.
Conclusions:
- Intravitreal ciprofloxacin at doses of 500 and 1000 micrograms demonstrates ocular toxicity in rabbits.
- A dose of 250 micrograms of intravitreal ciprofloxacin appears safe and achieves therapeutic concentrations for at least 24 hours.
- Further investigation into the 250 microgram dose is warranted for treating intraocular infections.