Evaluation of intraocular pharmacokinetics and toxicity of prinomastat (AG3340) in the rabbit

To determine the ocular pharmacokinetics, physiological and histological ef fects of prinomastat (a matrix metalloprotease inhibitor), a total of seven ty-seven eyes of New Zealand White rabbits received intravitreous and subte non injections of prinomastat or of acidified water vehicle as control. Dos es of 0.5 mg in 0.05 mt of prinomastat or acidified water were used for int ravitreal injection. For the subtenon injections, doses of 5 mg prinomastat in 0.5 mt of acidified water were administered in the superotemporal quadr ant. Intraocular pharmacokinetics were determined by analyzing vitreous sam ples at different postinjection time points using Liquid Chromatography-Mas s Spectroscopy/Mass Spectroscopy (LC-MS/MS). The toxicity was evaluated by biomicroscopy, electroretinography (ERG), pneumatonometry, and histology, N o toxicity was found with either administration method. At day 14 after int ravitreal injection, levels of prinomastat in the vitreous and choroid were 1.4 ng/mg and 7.8 ng/mg, respectively. The retinal levels of prinomastat w ere 22 ng/mg at 24 hr and dropped below 1 ng/mg at 48 hr. Prinomastat remai ned well above minimum effective concentration in the choroid for at least four weeks after a single intravitreal injection, suggesting that local int ravitreal injection may have potential in treating choroidal neovasculariza tion.