Skin, adipose tissue and plasma levels of acitretin with rare occurrence of esterified acitretin during long-term treatment.
In a previous study acitretin and its 13-cis-metabolite were monitored in the plasma and epidermis of healthy volunteers. They were given 50 mg of trans-acitretin daily. No drug accumulation was observed in the skin, nor in the plasma. The purpose of the present study was to extend the data from non-psoriatic to psoriatic (n = 11) subjects, treated for at least 1 month with 25 mg acitretin. Plasma, skin biopsies and subcutaneous fat samples were analysed using HPLC. Trough levels of acitretin in skin were below the quantification limit, increasing to 28 +/- 16 ng/g within 5 h after dosing. Fat tissue levels exceeded those of skin, with values of 98 +/- 71 ng/g within 5 h after drug intake. In 2 patients, additional samples were taken 3 days post-therapy. Here, concentrations were below the quantification limit in adipose tissue, confirming that acitretin is not stored in subcutaneous fat. Esterification of acitretin into etretinate was observed in 2 subjects. This observation illustrates the recently described new metabolic pathway for acitretin. On both occasions, the unexpected ethylester metabolite was extensively stored in fat tissue.
Meyer
E
E
Laboratory of Medical Biochemistry and of Clinical Analysis, University of Ghent, Belgium.
de Bersaques
J
J
Lambert
W E
WE
de Leenheer
A P
AP
Kint
A H
AH
D017255:Acitretin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D000368:Aged; D002851:Chromatography, High Pressure Liquid; D004951:Esterification; D005050:Etretinate / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D007642:Keratosis / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
D005050:Etretinate; D017255:Acitretin