MONITORING OF ISOTRETINOIN THERAPY BY MEASURING THE PLASMA-LEVELS OF ISOTRETINOIN AND 4-OXO-ISOTRETINOIN - A USEFUL TOOL FOR MANAGEMENT OF SEVERE ACNE

Background: Isotretinoin for oral therapy in severe acne conglobata an d acne nodulocystica represents a significant achievement; however, th e drug exerts several mucocutaneous and systemic adverse effects, besi des its teratogenic potency. Objective: The aim of this study was to i nvestigate the plasma levels of isotretinoin and of LC-oxo-isotretinoi n over long-term treatment of severe acne and to assess any correlatio n with the given dose, the clinical improvement and the occurrence of side effects. Methods: Forty-one patients with severe acne and acne-re lated disorders were studied under long-term oral intake of isotretino in. Therapeutic effects and side effects were evaluated prior, during and at the end of therapy. The plasma levels of isotretinoin and of it s major metabolite 4-oxoisotretinoin were measured by reversed-phase H PLC and were correlated with the administered oral dose and the number and frequency of side effects. Results: Dose-dependent plasma levels of isotretinoin and its metabolite were observed. At a mean dosage of 0.75-1.0 mg/kg/day, 404 +/- 142 ng/ml were measured, whereas the plasm a levels of 4-oxo-isotretinoin were 1-2x higher. The plasma levels cor related well with the orally administered dose of isotretinoin and the observed mucocutaneous side effects. Conclusion: The study demonstrat es that measuring of the plasma levels may be a helpful tool to monito r the individual therapeutic dose regimen in patients with severe acne in order to minimize undesired side effects and to control oral intak e.