The continuous delivery of drugs to specified target sites within the eye with minimum side effects is a very desirable goal in the management of chronic ocular diseases or conditions including glaucoma, comitant strabismus, bacterial and viral infections, inflammatory diseases and trachoma. The overall objective of this proposed research is to achieve this goal by employing the prodrug approach. Prodrugs are chemical modifications of existing drugs with the potential to modify their absorption, side effects, or duration of action, and must be converted enzymatically to the parent drugs before the intended pharmacological activity is obtained. Consequently, it is essential to establish the availability as well as activities of the enzymes in vivo prior to prodrug design and administration. to this end, this research seeks to delineate the esterase distribution and activities in the ocular fluids and tissues of both albino and pigmented rabbits. These fluids include tears and aqueous humor; and the tissues include cornea, iris and ciliary body. Using prototype esters including pilocarpine and dipivalyl epinephrine, the esterases will be studied with respect: (1) substrate specificity, i.e. whether they prefer aliphatic, aromatic or cyclic esters, (2) susceptibility to substrate and product inhibition, and (3) dependence of the rate of enzymatic hydrolysis on the ester's chain length. Such information will be derived from the initial rate of enzymatic hydrolysis of a selected ester, which in turn will be determined by the pH-stat method under specified experimental conditions. The usefulness of this information wilil be evaluated through the design of ester prodrugs for salicylic acid to be released over a specified period of time in the cornea. Based on these results, guidelines will be formulated for ocular ester prodrug design with the clinical goal of improving the therapeutic efficacy of the drugs intended for the diseases mentioned above. A further significance of this research is that it would be possible to anticipate the extent of lost of drugs containing ester linkages through hydrolysis, and to determine the basis underlying the differences in the ocular esterase activities of albino and pigmented rabbits.