A new approach to drug penetration study.

To investigate the route of drug penetration into the eye and drug distribution patterns in the lens, the distribution of aldose reductase inhibitor (AL-04114) in the lens was measured in short term bovine lens organ cultures and topical administration to rabbit eyes. A micro lens sectioning technique was applied to determine drug localization within the lens. Freshly enucleated bovine lenses were incubated with different concentrations of an ARI (AL-04114)-containing medium for 3 hours. For the in vivo study, 40 microliters of 0.3% AL-04114 (ophthalmic solution) were administered into the cul de sacs of rabbits 3 times at 3 hour intervals. After the incubation and final instillation, the lenses were divided into an equatorial ring and several layered sections. Drug concentration was measured by a reversed-phase HPLC system. The drug concentration was highest within the layer of the posterior shallow cortex > equator > anterior shallow cortex. No drug penetration was observed in the anterior/posterior deeper cortex or nucleus in vitro. The in vivo experiment revealed drug penetration in the equator and anterior shallow cortex, but not in any other lens layers. Drug penetration was detected within the serum and aqueous humor, but not in the vitreous.