CONVERSION OF ACITRETIN TO ETRETINATE IN PSORIATIC PATIENTS IS INFLUENCED BY ETHANOL

Acitretin has recently been introduced to replace etretinate in the tr eatment of severe psoriasis due to a considerable shorter terminal hal f-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, 1 0 patients with severe psoriasis were treated with 30 mg acitretin dai ly for 3 months. Seven patients had detectable mean steady-state plasm a etretinate concentrations in the range of 2.5 to 56.7 ng/ml. Four of the patients showed teratogenic levels of plasma etretinate. Consumpt ion of alcohol appeared to be an important contributing factor for the formation of etretinate. As judged from the dose- and body-weight-nor malized AUC values (AUC(cor)) there was a great inter-individual varia tion (sixfold) in the systemic availability of acitretin. After discon tinuation of therapy, the rate of elimination of both acitretin (t1/2 range 1.0 to 25.4 d) and 13-cis-acitretin (t1/2 range 1.5 to 25.7 d) w as found to be related to the observed mean steady-state level of etre tinate as evidenced by a longer terminal t1/2 of patients with high le vels 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 t o 59.3 d). The risk of metabolic formation of etretinate in acitretin recipients makes it impossible to draw any definite conclusion with re gard to recommendation of length of anti-conceptive period following a citretin therapy in psoriatics. Monitoring of plasma etretinate levels in acitretin-treated fertile women is advisable.