PT - JOURNAL ARTICLE AU - Meera Tugnait AU - Edward M. Hawes AU - Gordon McKay AU - Allan E. Rettie AU - Robert L. Haining AU - Kamal K. Midha TI - <em>N</em>-Oxygenation of Clozapine by Flavin-Containing Monooxygenase DP - 1997 Apr 01 TA - Drug Metabolism and Disposition PG - 524--527 VI - 25 IP - 4 4099 - http://dmd.aspetjournals.org/content/25/4/524.short 4100 - http://dmd.aspetjournals.org/content/25/4/524.full SO - Drug Metab Dispos1997 Apr 01; 25 AB - 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 μM) was very similar to the mean value obtained in these laboratories for the microsomal preparations of seven human livers. The American Society for Pharmacology and Experimental Therapeutics