Novel site-specific chemical delivery system as a potential mydriatic agent: Formation of phenylephrine in the iris-ciliary body from phenylephrone chemical delivery systems

The objective of this study was to test the three novel ester derivatives o f phenylephrone (isovaleryl, phenylacetyl, and pivalyl esters) as potential site-specific chemical delivery systems. The mydriatic effect and ocular d istribution/metabolism of these compounds were studied by topical applicati on to the eyes of normal rabbits. It was assumed that a reduction-hydrolysi s sequence could produce the active phenylephrine in the iris-ciliary body tissues. All the derivatives showed a more pronounced mydriatic effect than that of phenylephrine, whereas phenylephrone was completely devoid of any mydriatic activity. Phenylacetyl ester was the most potent drug, with short duration of action, and showed maximum activity in the presence of 0.01% b enzalkonium chloride without causing any visible irritation to the rabbit e ye. Administration of the novel compounds to the eyes of the rabbits showed no traces of phenylephrine in the systemic circulation, contrary to topica l administration of phenylephrine. Phenylephrone was detected in different compartments of the eye, whereas phenylephrine was present only in the iris -ciliary body tissues following administration of phenylacetyl ester. The c onversion of phenylephrone esters to the active drug, phenylephrine, and th us their subsequent activity was dependent on the physicochemical character istics of the drugs. The results suggest the potential use of phenylacetyl ester as a potent short-term mydriatic agent without systemic side effects. (C) 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association.