title: Finite element modeling of drug distribution in the vitreous humor of the rabbit eye.
abstract: Direct intravitreal injection of drug is a common method for treating diseases of the retina or vitreous. The stagnant nature of the vitreous humor and surrounding tissue barriers creates concentration gradients within the vitreous that must be accounted for when developing drug therapy. The objective of this research was to study drug distribution in the vitreous humor of the rabbit eye after an intravitreal injection, using a finite element model. Fluorescein and fluorescein glucuronide were selected as model compounds due to available experimental data. All required model parameters were known except for the permeability of these compounds through the retina, which was determined by fitting model predictions to experimental data. The location of the intravitreal injection in the experimental studies was not precisely known; therefore, several injection locations were considered, and best-fit retinal permeability was determined for each case. Retinal permeability of fluorescein and fluorescein glucuronide estimated by the model ranged from 1.94 x 10(-5) to 3.5 x 10(-5) cm s(-1) and from 0 to 7.62 x 10(-7) cm s(-1), respectively, depending on the assumed site of the injection. These permeability values were compared with values previously calculated from other models, and the limitations of the models are discussed. Intravitreal injection position was found to be an important variable that must be controlled in both experimental and clinical settings.
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, Ontario, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Friedrich
authors.forename: Y L
authors.initials: YL
authors.lastname: Cheng
authors.forename: B
authors.initials: B
authors.lastname: Saville
mesh_terms: D000465:Algorithms; D000818:Animals; D019793:Fluorescein; D005452:Fluoresceins / Q000493:pharmacokinetics*; D008954:Models, Biological; D011817:Rabbits; D012160:Retina / Q000187:drug effects; D014018:Tissue Distribution / Q000187:drug effects; D014822:Vitreous Body / Q000187:drug effects* / Q000378:metabolism
chemical_list: D005452:Fluoresceins; C041357:fluorescein glucuronide; D019793:Fluorescein