Comparison of ocular disposition of free pivalic acid and pivalic acid esterified in dipivefrin.

Dipivefrin, a diester of pivalic acid and epinephrine that is used in the treatment of glaucoma, has been shown to be hydrolyzed in the cornea, and the ocular pharmacokinetics of the active moiety, epinephrine, have been determined. A comparison of the ocular disposition of the pivalic acid released by hydrolysis of dipivefrin and that of topically applied free pivalic acid showed that the released pivalic acid is not metabolized in the eye and is rapidly eliminated from the eye with no apparent sequestration in ocular tissues. In addition, results of two methods for preparing ocular tissues for analysis of drug distribution indicated that freezing and thawing processes can lead to redistribution of materials in ocular tissues.