Therapeutic drug monitoring of clozapine

Clozapine is a prototypical atypical antipsychotic used to treat severe schizophrenia and for which a therapeutic drug monitoring (TDM) is quite commonly proposed. Clozapine is rapidly absorbed (maximum concentration reached within 1 to 4 hours), and is extensively metabolized in the liver by CYP1A2 to an active metabolite (and to a lesser extent, to inactive metabolites via other enzymes). Its half-life is 8 to 16 h. A therapeutic range has been proposed for clozapine as some studies have reported both a relationship between low plasmatic concentrations and resistance to treatment (threshold level is likely between 250 and 400 mu g/L), and a relationship between high plasmatic concentrations and an increase in the occurrence of toxicity (alert level = 1000 mu g/L). Given the data obtained in different studies, the TDM was evaluated for this molecule, to recommended. (C) 2016 Societe francaise de pharmacologie et de therapeutique. Published by Elsevier Masson SAS. All rights reserved.