SIMULTANEOUS DIFFUSION AND METABOLISM OF BETAMETHASONE 17-VALERATE INTHE LIVING SKIN EQUIVALENT

Simultaneous diffusion and metabolism of betamethasone 17-valerate was studied using betamethasone 17-valerate, betamethasone 21-valerate, a nd betamethasone as permeants. These corticosteroids were suspended in silicone adhesive and applied to an artificial living skin equivalent (LSE) for 72 h. When betamethasone was applied, no metabolites were d etected in the receptor medium. Conversely, with betamethasone 21-vale rate application, only betamethasone but no betamethasone 21-valerate was detected in the receptor medium indicating the metabolism of the l atter by skin esterases. When tested with the theory for simultaneous diffusion and metabolism, the result is consistent with the enzyme rat e constant in the LSE homogenate measured in a previous study. When be tamethasone 17-valerate was applied to the LSE, more than half of the total amount of corticosteroids detected in the receptor medium was un changed, consistent with the previously reported chemical (as opposed to enzymatic) degradation half-life of about 8 h. This result also ind icated that very little metabolism of betamethasone 17-valerate occurr ed in the skin.