Oral acitretin in psoriasis: drug and vitamin A concentrations in plasma, skin and adipose tissue.
The purpose of the present study was to determine the concentrations of acitretin and its main metabolite, 13-cis acitretin, in epidermis, subcutis and plasma in twelve psoriatic patients treated with 30 mg acitretin orally daily for 6 months. In addition, endogenous concentrations of vitamin A were monitored. Blood samples and biopsies from normal appearing skin were obtained prior to therapy, after 1 and 6 months of treatment and finally 1 month after cessation of therapy. Using a highly sensitive liquid chromatography method concentrations of synthetic retinoids and endogenous retinoid (retinol, 3,4-didehydroretinol) were analysed in hydrolyzed tissue samples and plasma. Steady-state concentration of acitretin in epidermis (17 +/- 9 ng/g) was reached within 1 month of therapy. There was a significant correlation between the individual plasma trough value and the epidermal concentration of acitretin after 1 month of therapy. The acitretin concentrations in subcutis varied from 15 to 1437 ng/g, but the mean values at 1 and 6 months of therapy were similar (177 and 227 ng/g, respectively). After stopping therapy the acitretin level was below the detection limit in both epidermis and serum within 1 month in 9 out of 12 patients. In contrast, only 3 of the patients were negative for acitretin in subcutis biopsies obtained 1 month after stopping therapy. The occurrence of a presumed tissue contaminator with characteristics similar to 13-cis acitretin prevented quantitation of this metabolite in many subcutis samples. The epidermal, subcutis and serum composition of retinol and 3,4-didehydroretinol remained unchanged during therapy, indicating no or only minimal interaction between acitretin and endogenous vitamin A metabolism.
Larsen
F G
FG
Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark.
Vahlquist
C
C
Andersson
E
E
Törma
H
H
Kragballe
K
K
Vahlquist
A
A
D017255:Acitretin; D000273:Adipose Tissue / Q000378:metabolism*; D000284:Administration, Oral; D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy / Q000378:metabolism; D012867:Skin / Q000378:metabolism*; D014212:Tretinoin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D014801:Vitamin A / Q000032:analysis*
D014801:Vitamin A; D014212:Tretinoin; D017255:Acitretin