Disposition of timolol and inulin in the rabbit eye following corneal versus non-corneal absorption

Abstract

This study describes an investigation of the corneal versus non-corneal penetration routes of topically applied drugs in the eye. The time course of ocular distribution and disposition of topically applied timolol and inulin following corneal and non-corneal absorption was investigated. It was shown that non-corneal absorption may contribute significantly to drug penetration into intraocular tissues. Such ‘productive’ non-corneal drug penetration involves drug permeation across the conjunctiva and the underlying sclera. Drug absorbed by this route essentially bypassed the anterior chamber and distributed primarily in the uveal tract and vitreous humor. Non-corneal absorption may be important for drugs that are poorly absorbed across the cornea. This was demonstrated using inulin as a model of a large molecular weight compound with poor corneal permeability. Overall, 40% of the absorbed amount of inulin in the eye, and even larger proportions in selected ocular tissues could be attributed to non-corneal penetration. These studies suggest that anterior chamber levels may not be an appropriate measure of the ocular bioavailability for all drug delivery systems. The primary factor limiting the extent of non-corneal penetration of drugs into the eye appears to be the concurrent systemic loss of drug via the ocular vasculature.