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 exte nd 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 ac itretin 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. I n 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. Esterifi cation of acitretin into etretinate was observed in 2 subjects. This o bservation illustrates the recently described new metabolic pathway fo r acitretin. On both occasions, the unexpected ethylester metabolite w as extensively stored in fat tissue.