Acitretin is converted to etretinate only during concomitant alcohol intake

Background Acitretin has replaced etretinate in the treatment of various di sorders of keratinization due to a considerably shorter terminal half-life. Possible esterification of acitretin to etretinate in the presence of etha nol has been reported. Objectives To determine the plasma concentrations of etretinate as a metabolite in patients with various disorders of keratiniz ation after multiple acitretin dosing, and to assess the influence of alcoh ol consumption using a questionnaire. In addition, to study the influence o f alcohol consumption on the risk of metabolic formation of etretinate. Patients/methods Eighty-six acitretin (Neotigason(R), Roche)-treated outpat ients from three centres provided pre-dose (trough) samples for determining plasma concentrations of acitretin and its metabolites 13-cis-acitretin an d etretinate. Patients received acitretin doses of between 0.1 and 1.3 mg k g(-1) daily. The concentrations of etretinate, acitretin and 13-cis-acitret in were determined by reverse-phase high-performance liquid chromatography. Results Of the 86 patients, 30 had detectable plasma etretinate levels. No etretinate was found in 20 patients who reported that they never drank alco hol, while etretinate was found in all 16 patients with an average weekly a lcohol consumption of > 200 g ethanol, corresponding to about 15 U (1 U equ als half a pint of standard beer or a wine glass of non-fortified wine). Et retinate was detected in 14 of 50 patients with a moderate weekly alcohol i ntake of up to 200 g ethanol. A trend linking higher alcohol intake with bo th higher risk of etretinate formation and higher etretinate levels was obs erved. The study also revealed that the ethylesterification only relates to acitretin (13-trans-) and not to the main metabolite 13-cis-acitretin, alt hough the latter compound showed higher plasma trough concentration levels at steady state. Conclusions Owing to the teratogenic potential and possible side-effects of oral retinoids, fertile women especially should be informed about the impo rtance of strict alcohol abstinence during treatment and for at least 2 mon ths after stopping therapy. In case of non-compliance with alcohol abstinen ce a post-therapy contraceptive period of 2-3 years should be recommended.