Administration of Anecortave Acetate in a Finite Element Physiologic Ocular Pharmacokinetic Model

Abstract

Purpose: : A finite element model with regional partitioning is applied to four experiments to predict the outcome of different modes of rabbit ocular administration of Anecortave Acetate.

Methods: : Partition coefficients are measured for drug between phosphate buffered saline and retina(R), choroid(C), and sclera(S). Diffusion coefficients are determined from transport through intact R/C/S membrane or through sclera denuded of R/C, applying mathematics for transport through bilaminate membranes. A transscleral drug delivery device (TS/DDD) located a drug tablet behind the sclera. The distribution of drug and metabolite were measured in R,C,S in a 10mm disc centered under the payload. In a separate experiment a 20 uL bolus was injected in the outer vitreous(V) near the pars plana. Eyes were enucleated, frozen, the posterior section was quartered with one quarter centered on the dose. Drug was measured in V, R, C and S for each quadrant.

Results: : TS/DDD: Concentration is uniform under the payload, decaying rapidly from the payload. Drug concentrations are S>C>R>>V, consistent with the data. Bolus: The long term drug decay rate is well predicted, with reasonable ratios for the relative amounts in the various tissue types and in the dose and adjacent quadrants.

Conclusions: : The nonlinear interaction between diffusion and partition coefficients requires them to be determined in separate in vitro experiments. The model is able to predict the outcome of very different in vivo experiments. This method is proposed for predicting the distribution and elimination of any ocular drug.

Keywords: retinal neovascularization • choroid: neovascularization • sclera