N-OXYGENATION OF CLOZAPINE BY FLAVIN-CONTAINING MONOOXYGENASE

The involvement of FMO in the N-oxygenation of CLZ was investigated by use of purified FMOs and human liver microsomes that contained the me an amount of immunoreactive FMO3 relative to other human liver microso mal preparations in a liver bank. In the microsomal preparation the in volvement of FMO was indicated through enzyme inhibition by methimazol e, heat inactivation, and protection against heat inactivation by NADP H. Also the Michaelis-Menten kinetic constant; K-M determined for CLZ N-oxidation catalyzed by purified human FMO3 (324 mu M) was very simil ar to the mean value obtained in these laboratories for the microsomal preparations of seven human livers.