Site of ocular hydrolysis of a prodrug, dipivefrin, and a comparison of its ocular metabolism with that of the parent compound, epinephrine.

Dipivefrin is a prodrug of epinephrine which is hydrolyzed to epinephrine after absorption into the eye. The major site of this hydrolysis is shown to be the cornea. Some dipivefrin is absorbed unchanged into ocular tissues, but most appears as epinephrine and its metabolites within 15 min after topical application. Metanephrine is the major metabolite of epinephrine found in ocular tissues. It is found as soon as 15 min aftter application of either dipivefrin or epinephrine and appears in all the tissues tested. The data indicate that the peinephrine which is liberated by hydrolysis of topically applied dipivefrin is metabolized similarly to topically applied epinephrine. The monoamine oxidase metabolites of epinephrine appear 1 to 3 hr after treatment and are found mainly in the aqueous humor. After ocular application of either compound there appear to be uptake and storage of the exogenous epinephrine in the iris plus ciliary body. There is also some storage of unmetabolized epinephrine in the cornea.