N-oxygenation of clozapine by flavin-containing monooxygenase.
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Tugnait M, Hawes EM, McKay G, Rettie AE, Haining RL, Midha KK
N-oxygenation of clozapine by flavin-containing monooxygenase.
Drug Metab Dispos. 1997 Apr;25(4):524-7.
- PubMed ID
- 9107553 [ View in PubMed]
- 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.
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