Ocular penetration of intravenously administered colistin in rabbit uveitis model.

Abstract

The purpose of this study was to evaluate the ocular distribution of intravenously administered colistin in a rabbit uveitis model. Colistin, a polypeptide antibiotic against the multidrug-resistant (MDR) Gram-negative organisms, was given intravenously to rabbits at 5 mg/kg of body weight starting 24 h after induction of uveitis by intravitreal endotoxin injection. Colistin concentrations were determined by high-performance liquid chromatography-mass spectrometry assay in the aqueous humor, vitreous humor, and plasma 0.5, 3, 6, and 24 h after administration of a single dose. The maximum colistin concentrations (mean±standard deviation) were found 0.5 h after the end of the intravenous administration and were 9.48±2.0 μg/mL in plasma and 0.62±0.07 μg/mL in the aqueous humor of the inflamed eye. After 24 h, no drug was detectable in the aqueous of the inflamed eyes. Colistin was undetectable in the aqueous of contralateral normal eyes at all time points. Drug concentrations in all the vitreous samples from both inflamed and normal eyes were undetectable, except at the 3-h inflamed eye group, and a colistin concentration of 0.02±0.01 μg/mL was found. Plasma levels of colistin fell to 0.93±0.07 and 0.24±0.08 μg/mL, after 3 and 6 h, respectively, and were not detectable 24 h after the given dose. In our model, colistin did not reach therapeutically relevant levels in the aqueous and in the vitreous humor of rabbit eyes. The findings suggest a limited role for intravenously administered colistin in the treatment of Gram-negative bacterial endophthalmitis.