In vitro transport and partitioning of AL-4940, active metabolite of angiostatic agent anecortave acetate, in ocular tissues of the posterior segment.

Purpose. The purpose of this study was to evaluate partitioning into and transport across posterior segment tissues (sclera, retinal pigment epithelium (RPE)–choroid) of AL-4940, the active metabolite of angiostatic cortisene anecortave acetate (AL-3789). Methods. Transport of [14C]-AL-4940 was measured through RPE–choroid–sclera (RCS) and sclera, excised from Dutch Belted pigmented rabbits’ eyes, in the directions of scleral to vitreal (S→V) and vitreal to scleral (V→S) for 3 h at 37°C using Ussing chambers. Tissue integrity was monitored by transepithelial electrical resistance (TEER), potential difference (PD), and biochemical assay (LDH). Partitioning in RPE–choroid and sclera was determined separately for both [14C]-AL-4940 and [14C]-AL-3789. Mathematical analysis for bilaminate membranes used partitioning and transport data to derive diffusion coefficients for 2 tissue layers sclera and RPE–choroid. Results. Partitioning of drug in tissue was comparable for both [14C]-AL-4940 and [14C]-AL-3789. Part...