Cis-trans interconversion of acitretin in man.
The major plasma metabolite of acitretin (trans-acitretin) is its 13-cis isomer, cis-acitretin. Interconversion of cis-acitretin to trans-acitretin was demonstrated in man following administration of a single oral dose of cis-acitretin. Plasma concentrations of Ro 13-7652 (cis-acitretin) and Ro 10-1670 (trans-acitretin) were much higher after cis-acitretin administration than after trans-acitretin administration. Surprisingly, these high concentrations were not associated with a clear therapeutic effect in dermatoses (e.g. psoriasis) which are usually responsive to oral retinoids. Interactions between the cis and trans isomers formed in vivo may explain the difference in therapeutic activity of each stereoisomer when administered orally.
Geiger
J M
JM
Department of Clinical Research, F. Hoffmann-La Roche & Co. Ltd., Basel, Switzerland.
Brindley
C J
CJ
D017255:Acitretin; D000328:Adult; D000368:Aged; D000818:Animals; D001711:Biotransformation; D003872:Dermatitis / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy / Q000378:metabolism; D051381:Rats; D012871:Skin Diseases / Q000188:drug therapy / Q000378:metabolism; D013237:Stereoisomerism; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use
D014212:Tretinoin; D017255:Acitretin