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 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.
Tugnait
M
M
College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Canada.
Hawes
E M
EM
McKay
G
G
Rettie
A E
AE
Haining
R L
RL
Midha
K K
KK
D003024:Clozapine / Q000493:pharmacokinetics*; D006801:Humans; D008862:Microsomes, Liver / Q000201:enzymology; D010100:Oxygen / Q000378:metabolism*; D010105:Oxygenases / Q000378:metabolism*
D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming); D003024:Clozapine; D010100:Oxygen