Site- and stereospecific ocular drug delivery by sequential enzymatic bioactivation.

Intraocular enzymes convert the ketoxime analogues of some beta-adrenergic blockers via a sequential bioactivation process involving hydrolysis to the corresponding ketones followed by reduction to the aryloxyaminoalcohols, which then exert known and predictable physiological and pharmacological effects only at the site of the action--i.e., in the eye--without any systemic side effects. The sequential nature of the process is highlighted by the observation that the administration of the ketone intermediate also leads to its conversion to the beta-adrenergic antagonist, the active compound. The reduction is stereospecific resulting in the formation of the more potent S-(-)-form of the drug, thus providing prospect to glaucoma treatment. The same activation process of the ketoximes does not take place systemically, thus administration of these ketoximes does not produce cardiovascular effects.