Pharmacokinetics of intravenously administered tigecycline in eye compartments: an experimental study.

Abstract

PURPOSE: The purpose of this study was to evaluate the ocular distribution of intravenously administered tigecycline in a rabbit uveitis model. METHODS: Tigecycline, which has a broad spectrum of activity against many gram-positive, gram-negative, and anaerobic organisms, was given intravenously to rabbits at 7 mg/kg of body weight starting 24 h after induction of uveitis by intravitreal endotoxin injection. Tigecycline concentrations were determined by high performance liquid chromatography-mass spectrometry (LC-MS/MS) assay in the aqueous humor, vitreous humor, and plasma 1, 3, 6, and 24 h after administration of a single dose. RESULTS: The maximum concentrations were found within 1 h after the end of the intravenously given tigecycline, and were 1,308.60 ± 301.76 ng/mL in plasma, 181.40 ± 51.32 ng/mL in vitreous humor and 145.00 ± 55.29 ng/mL in aqueous humor of the inflamed eye. After 24 h, no drug was detectable in the aqueous and vitreous of the normal eyes, whereas small amounts of drug were detectable in inflamed eyes and in plasma. CONCLUSIONS: Tigecycline did not reach therapeutically significant levels in the aqueous and the vitreous humor of rabbit eyes. The findings suggest a limited role for intravenously administered tigecycline in the treatment of bacterial endophthalmitis.