Studies on the Pharmacokinetics and Metabolism of Prednicarbate after Cutaneous and Oral Administration

Abstract

Prednicarbate (PC) is a nonhalogenated derivative of prednisolone which is used for the local treatment of corticoid-sensitive skin diseases. In this study, the pharmacokinetics and the metabolism of PC in humans are investigated after cutaneous ointment application (75 mg PC) and after systemic oral administration (40 mg PC) in 8 healthy volunteers. In addition, the possible suppression of endogenous cortisol secretion by both application forms was monitored. After oral administration no intact PC, but significant levels of the first metabolite prednisolone-17-ethylcarbon-ate (PRED-17-EC) were determined. PRED-17-EC was further metabolized with a half life of 1.6 h to prednisolone. After percutaneous administration neither PC nor other known metabolites could be detected system-ically. The low systemic bioavailability after dermal application was also reflected in an unchanged cortisol secretion pattern. According to animal studies our metabolic studies in humans suggest that the prednisolone-17-ester PRED-17-EC, which has a receptor binding affinity comparable to that of dexamethasone is the pharmacologically active compound. As PRED-17-EC subsequently undergoes an inactivation step to the low active prednisolone this may be the reason for the dissociation of good local efficacy and low systemic side effects.

Contact allergy to corticosteroids

“…Prednicarbate is rapidly hydrolyzed at position C 21 . The resulting intermediary product, prednisolone-17-ethylcarbonate, metabolizes slowly into prednisolone (47).…”

Topical Glucocorticoids with Improved Risk-Benefit Ratio

“…Pharmacokinetic studies, including experiments concerning biotransformation in animals [32] and humans, [33] have revealed that prednicarbate is metabolised to prednisolone 17 -ethylcarbonate and then to prednisolone in the skin as well as in the liver, [34]lungsI35] and synovial tissue. [36,37] The former step is considerably faster than the latter one.…”

Atopic dermatitis – topical therapy: Do patients apply much too little?

“…Prednicarbate is a non-halogenated derivative of prednisolone (prednisolone-17-ethyl carbonate-21-propionate), which is used for the local treatment of skin diseases responsive to topical glucocorticoids. It has good local efficacy and low systemic side effects (23).…”