PERMEABILITY CHARACTERISTICS OF PRIMARY CULTURED RABBIT CONJUNCTIVAL EPITHELIAL-CELLS TO LOW-MOLECULAR-WEIGHT DRUGS

Purpose. To evaluate the permeability characteristics of primary cultu red rabbit conjunctival epithelial cell (RCEC) layers to low molecular weight drugs of varying lipophilicity. Methods. H-3-mannitol; hydroph ilic sotalol and atenolol; moderately lipophilic metoprolol, timolol, propranolol; and highly lipophilic betaxolol were used as model compou nds. Results. The conjunctival apparent permeability coefficient (P-ap p) of mannitol (1x10(-7) cm/s) was 2.4 times lower than that of the mo st hydrophilic beta-blocker, sotalol (P-app=2.4x10(-7) cm/s). Differen ces in the degree of tightness of the epithelial cell layers brought a bout a 30-fold difference in the transport of atenolol in favor of the leaky cell layers, while not affecting the transport of the Lipophili c drug, propranolol. Within the log partition coefficient (PC) range o f -0.62 (sotalol) and 3.44 (betaxolol), there was a hundred-fold diffe rence in the P-app. A sigmoidal curve was used to depict the influence of lipophilicity on solute permeation across conjunctival epithelial cell layers. An effective half-maximal P-app was observed at a log PC value of 1.2. Conclusions. These findings on the lipophilicity effect on drug transport are generally similar to those reported for the isol ated rabbit conjunctiva, suggesting the utility of cultured rabbit con junctival epithelial cell layers as an in vitro model for evaluating d rug transport.