Skin, adipose tissue and plasma levels of acitretin with rare occurrence of esterified acitretin during long/term treatment.

Abstract

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.