Intravitreal kinetics of macromolecules in rats and rabbits: evaluation with ocular fluorophotometry

Abstract

AbstractPurposeRats and rabbits are widely used in preclinical ocular pharmacodynamics and pharmacokinetics. Despite the wide application in the evaluation of intravitreally injected drugs, there is no information about scaling of vitreal kinetics between rats and rabbits. In this study, the vitreal kinetics of macromolecules in rats and rabbits were evaluated using in vivo fluorophotometry.MethodsIn order to elucidate the pharmacokinetics of macromolecules and drug delivery systems we used ocular fluorophotometry that is a noninvasive technique for non‐invasive and quantitative measurement of fluorescence signals from the eye. Molecules with different molecular weights (peptide 4.5 kD, FITC‐hyaluronic acid 770 kD, FITC‐dextran 500 kD and fluorescein 330 D, FITC‐dextran 10 kD and FITC‐dextran 150 kD) were injected to the vitreous of rabbits and rats. The concentrations of these molecules were quantified in the vitreous at various time.Results and DiscussionThe data were used to calculate kinetic parameter, such as vitreal elimination half‐life and clearance. For example, the vitreal elimination half‐lives of FITC‐hyaluronic acid 770 kD in rabbits and rats were about 280 hr and 9 hr, respectively. Overall the vitreal elimination half‐lives of the compounds in the rats were much faster than in the rabbits. Since rats are widely used in the retinal pharmacodynamics studies, the fast elimination of macromolecules from the rat vitreous should be taken into account when scaling the doses from rats to rabbits and man.