Esterase activity in excised and reconstructed human skin - Biotransformation of prednicarbate and the model dye fluorescein diacetate

Due to the enhancement of dermal absorption, lipophilic, bioconversible drugs or prodrugs such as esters are often used in the topical treatment of skin disease. Preclinical drug development will take profit from a human-based test procedure based on standardised and widely available material, because species differences are only sparsely documented and ester cleavage can influence both therapeutic and adverse effects. Prednicarbate, a prednisolone diester, was investigated in parallel to the probe fluorescein diacetate in excised and reconstructed human skin and dermal cells to compare cutaneous esterase activity. An identical rank order of prednicarbate biotransformation and enzyme activity enables to predict drug metabolism by enzyme activity as measured by the probe.