Determination of acitretin and 13-cis-acitretin in skin.
The aim of the study was to investigate the concentrations of Ro 10-1670 (acitretin) and its isomeric metabolite Ro 13-7652 (cis-acitretin) after multiple oral dosing of acitretin. We used a highly sensitive HPLC method for simultaneous determination of the 2 retinoids with a quantification limit of 2 ng/ml in plasma and 10 ng/g in total skin (epidermis and dermis). In hairless rats receiving orally 8 mg/kg acitretin once daily during 8 days, blood and skin samples were taken at different time points between 5 and 96 h after the last dose. After 96 h, appreciable concentrations of Ro 10-1670, but not Ro 13-7652 could be measured in the skin, whereas both isomers were below the quantification limit in plasma. In psoriatic patients treated with a once daily dose of 30 mg acitretin, blood samples and biopsies were taken after 1 month of treatment (i.e. under steady state conditions). 24 h after the last drug intake, skin concentrations of acitretin were approximately 10 times higher than those observed in plasma. Ro 10-1670 concentrations in the skin were approximately 3-5 times higher than for Ro 13-7652 and concentrations of both isomers were higher in lesional compared to uninvolved skin.
Laugier
J P
JP
Centre de Pharmacologie Clinique et d'Essais Thérapeutiques, CHU Timone, Marseille, France.
Berbis
P
P
Brindley
C
C
Bun
H
H
Geiger
J M
JM
Privat
Y
Y
Durand
A
A
D017255:Acitretin; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy; D051381:Rats; D012867:Skin / Q000032:analysis*; D013237:Stereoisomerism; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics / Q000627:therapeutic use
D014212:Tretinoin; D017255:Acitretin