Cutaneous biotransformation as a parameter in the modulation of the activity of topical corticosteroids

Abstract

The hydrolysis of betamethasone-17- and -21-valerates by hepatic and cutaneous esterases is studied with a view to explaining their different activity profiles. It is shown that the 17-ester is resistant to both esterases while the 21-ester is rapidly hydrolyzed to the free steroid alcohol. Earlier reports on the cutaneous enzymic transformation of the 17-ester fail to account for the spontaneous isomerization of the ester to the 21-ester and are therefore misleading. The resistance of the 17-ester to enzymic hydrolysis may also lead to a more pronounced reservoir effect and hence toxicity following application to the skin. This work provides useful information for the design of topically active steroids. © 1985.