Esterase distribution in the rabbit cornea and its implications in ocular drug bioavailability.
Being the major pathway by which topically applied ophthalmic drugs enter the eye, the cornea can control the amount of active drug ultimately absorbed by offering resistance to drug permeation and by metabolizing the drug during permeation. This research seeks to determine the esterase activity in the cornea and two of its component layers--epithelium and stroma-endothelium--so as to anticipate the extent to which drugs containing ester linkages will be metabolized during transport. This has been achieved by incubating corneal homogenates of albino and pigmented rabbits of various age groups with alpha-naphthyl acetate, the model substrate, and monitoring the fluorescence intensity due to alpha-naphthol as a function of time. The results indicate that: (1) esterase activity in the epithelium is approximately twice that in the stroma-endothelium; (2) esterase activity in the intact cornea is linearly related to those in the epithelium and the stroma-endothelium; and (3) the esterase activity in the cornea and its component layers varies with rabbit's age and strain. According to these results the bulk of esterase-mediated hydrolysis is expected to take place in the epithelium, so that the residence time of a drug in this tissue can have a significant impact on its ocular bioavailability.
D000818:Animals; D001682:Biological Availability; D003315:Cornea / Q000201:enzymology*; D004727:Endothelium / Q000201:enzymology; D004848:Epithelium / Q000201:enzymology; D004950:Esterases / Q000378:metabolism*; D006868:Hydrolysis; D007700:Kinetics; D008297:Male; D009284:Naphthols / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011817:Rabbits
D009284:Naphthols; D004364:Pharmaceutical Preparations; C005366:naphthyl acetate; D004950:Esterases