Conversion of Acitretin to Etretinate in Psoriatic Patients Is Influenced by Ethanol

Acitretin has recently been introduced to replace etretinate in the treatment of severe psoriasis due to a considerable shorter terminal half-life. The previously recommended 2-month anticonceptive period after acitretin treatment has been extended to 2 years after the detection of etretinate in certain acitretin recipients. In the present study, 10 patients with severe psoriasis were treated with 30 mg acitretin daily for 3 months. Seven patients had detectable mean steady- state plasma etretinate concentrations in the range of 2.5 to 56.7 ng/ml. Four of the patients showed teratogenic levels of plasma etretinate. Consumption of alcohol appeared to be an important contributing factor for the formation of etretinate. As judged from the dose- and body-weight-normalized AUC values (AUC_cor) there was a great inter-individual variation (sixfold) in the systemic availability of acitretin. After discontinuation of therapy, the rate of elimination of both acitretin (t_1/2 range 1.0 to 25.4 d) and 13-cis-acitretin (t_1/2 range 1.5 to 25.7 d) was found to be related to the observed mean steady-state level of etretinate as evidenced by a longer terminal t_1/2 of patients with high levels of etretinate in plasma. A mean terminal elimination half-life of etretinate was found to be 45.7 d ± 10.6 (mean ± SD; range 27.0 to 59.3 d). The risk of metabolic formation of etretinate in acitretin recipients makes it impossible to draw any definite conclusion with regard to recommendation of length of anticonceptive period following acitretin therapy in psoriatics. Monitoring of plasma etretinate levels in acitretin-treated fertile women is advisable.