Wei CP, Anderson JA & Leopold I
Ocular absorption and metabolism of topically applied epinephrine and a dipivalyl ester of epinephrine.

Invest Ophthalmol Vis Sci, 17(4): 315-321, 1978
ISSN: 0146-0404 Investigative Ophthalmology & Visual Science (PubMed)

Abstract
An analogue of epinephrine (EPI), dipivalyl epinephrine (DPE), has been found to reduce intraocular pressure (IOP) significantly at lower concentrations than EPI itself. In order to understand the reason for this increased activity, the ocular penetration, distribution, and metabolism of these two compounds were compared. About 10 times as much DPE as EPI was absorbed by rabbit eyes, with the cornea as the major repository for the increased amount of drug absorbed. Comparison of the partition coefficients of the two compounds showed DPE to be from 100 to 600 times as lipophilic as EPI. The radioactive materials found in the aqueous humor after treatment with either compound had the same mobility in a thin-layer chromatographic system. The data indicate that following the increased penetration of the lipophilic prodrug, DPE is hydrolyzed to EPI in the eye.