STUDIES ON THE PHARMACOKINETICS AND METABOLISM OF PREDNICARBATE AFTERCUTANEOUS AND ORAL-ADMINISTRATION

Prednicarbate (PC) is a nonhalogenated derivative of prednisolone whic h is used for the local treatment of corticoid-sensitive skin diseases . In this study, the pharmacokinetics and the metabolism of PC in huma ns are investigated after cutaneous ointment application (75 mg PC) an d after systemic oral administration (40 mg PC) in 8 healthy volunteer s. In addition, the possible suppression of endogenous cortisol secret ion by both application forms was monitored. After oral administration no intact PC, but significant levels of the first metabolite predniso lone-17-ethylcarbonate (PRED-17-EC) were determined. PRED-17-EC was fu rther metabolized with a halflife of 1.6 h to prednisolone. After perc utaneous administration neither PC nor other known metabolites could b e detected systemically. The low systemic bioavailability after dermal application was also reflected in an unchanged cortisol secretion pat tern. According to animal studies our metabolic studies in humans sugg est that the prednisolone-17-ester PRED-17-EC, which has a receptor bi nding affinity comparable to that of dexamethasone is the pharmacologi cally active compound. As PRED-17-EC subsequently undergoes an inactiv ation step to the low active prednisolone this may be the reason for t he dissociation of good local efficacy and low systemic side effects.