Studies on the pharmacokinetics and metabolism of prednicarbate after cutaneous and oral administration.
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-ethylcarbonate (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 systemically. 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.
Barth
J
J
Medizinische Klinik Bergmannsheil, Bochum, FRG.
Lehr
K H
KH
Derendorf
H
H
Möllmann
H W
HW
Höhler
T
T
Hochhaus
G
G
D000284:Administration, Oral; D000287:Administration, Topical; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000378:metabolism*; D001711:Biotransformation; D006207:Half-Life; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D011239:Prednisolone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics
D000893:Anti-Inflammatory Agents; D011239:Prednisolone; C035287:prednicarbate; D006854:Hydrocortisone