Elevated Plasma Clozapine Concentrations After Phenobarbital Discontinuation

Sir: Clozapine, an atypical antipsychotic drug, is used mainly for treatment-resistant schizophrenia. Its metabolism is quite complex and involves a number of human cytochrome P450 enzymes and flavin-containing monooxygenases. Among them, cytochrome P450 1A2 (CYP1A2) appears to be the main enzyme responsible for the metabolism of clozapine. However, other isozymes, including CYP3A3/4, might also partially mediate clozapine’s disposition.