title: N-oxygenation of clozapine by flavin-containing monooxygenase.
abstract: The involvement of FMO in the N-oxygenation of CLZ was investigated by use of purified FMOs and human liver microsomes that contained the mean amount of immunoreactive FMO3 relative to other human liver microsomal preparations in a liver bank. In the microsomal preparation the involvement of FMO was indicated through enzyme inhibition by methimazole, heat inactivation, and protection against heat inactivation by NADPH. Also the Michaelis-Menten kinetic constant; KM determined for CLZ N-oxidation catalyzed by purified human FMO3 (324 microM) was very similar to the mean value obtained in these laboratories for the microsomal preparations of seven human livers.
authors.affiliation: College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Tugnait
authors.forename: E M
authors.initials: EM
authors.lastname: Hawes
authors.forename: G
authors.initials: G
authors.lastname: McKay
authors.forename: A E
authors.initials: AE
authors.lastname: Rettie
authors.forename: R L
authors.initials: RL
authors.lastname: Haining
authors.forename: K K
authors.initials: KK
authors.lastname: Midha
mesh_terms: D003024:Clozapine / Q000493:pharmacokinetics*; D006801:Humans; D008862:Microsomes, Liver / Q000201:enzymology; D010100:Oxygen / Q000378:metabolism*; D010105:Oxygenases / Q000378:metabolism*
chemical_list: D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming); D003024:Clozapine; D010100:Oxygen