Delivery of antiglaucoma drugs: ocular vs systemic absorption.

In order to reduce the intraocular pressure antiglaucoma drugs must penetrate into the inner eye. Ocular bioavailability is determined by the ability of drug to penetrate through the cornea and conjunctiva/sclera, and on the other hand, by its elimination from the conjunctival sac. Major part of this elimination is by systemic drug absorption via conjunctiva. Typically conjunctival systemic absorption of drugs is an order of magnitude greater than their ocular absorption. In addition substantial systemic absorption of ophthalmic drugs takes place via nasal mucosa. Systemic absorption of antiglaucoma drugs like beta blocking agents may cause systemic side-effects. The risk of systemic side-effects might be decreased by increasing the ocular/systemic ratio of drug absorption. Several approaches can be used to improve ocular/systemic drug absorption ratio. Firstly, corneal drug permeability is improved. This can be done using different formulations or prodrug derivatives. Secondly, systemic absorption can be decreased e.g. with kinetic drug interactions or drug formulations. Thirdly, the rate of drug delivery can be changed thereby affecting especially the peak concentrations of drug in systemic circulation. Different methods for improvement of ocular delivery relative to the systemic absorption of antiglaucoma drugs are summarized and the impact of systemic pharmacokinetics on the viability of each approach is discussed.