Ocular delivery of the beta-adrenergic antagonist alprenolol by sequential bioactivation of its methoxime analogue.

Ocular delivery of alprenolol, a beta-adrenergic antagonist, by site-specific bioactivation of its methoxime analogue results in significant and prolonged decrease of the intraocular pressure in rabbits after topical administration. Alprenolone methoxime is stable in isotonic phosphate vehicle but undergoes enzymatic hydrolysis to the corresponding ketone in the eye. The ketone is then converted to alprenolol by a carbonyl reductase present in the iris-ciliary body. The benefit of this chemical delivery system approach includes the facile release of a potential antiglaucoma agent only at the site of the action; thus, unwanted systemic effects of the drug can be avoided.