title: N-desmethylclozapine, an insensitive marker of clozapine-induced agranulocytosis and granulocytopenia.
abstract: We reviewed the charts of 58 patients with treatment-refractory schizophrenia who were receiving clozapine, to determine if the drug's active metabolite, N-desmethylclozapine, is a biologic marker for impending clozapine-induced granulocytopenia and agranulocytosis. No significant correlation between granulocyte counts and patient demographic variables of clozapine and N-desmethylclozapine steady-state plasma concentrations, clozapine:N-desmethylclozapine ratio, age, gender, clozapine dosage, smoking status, and race were found. We believe N-desmethylclozapine is not a clinically useful marker for monitoring the effect of clozapine on granulocyte integrity. On the contrary, its plasma concentrations correlated positively with granulocyte counts.
authors.affiliation: College of Pharmacy, University of Iowa, Iowa City 52246, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Combs
authors.forename: P J
authors.initials: PJ
authors.lastname: Perry
authors.forename: K A
authors.initials: KA
authors.lastname: Bever
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000097:blood; D000380:Agranulocytosis / Q000097:blood / Q000139:chemically induced*; D014150:Antipsychotic Agents / Q000009:adverse effects*; D003024:Clozapine / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000097:blood; D005260:Female; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D044469:Racial Groups; D012189:Retrospective Studies; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy; D012727:Sex Characteristics; D012907:Smoking / Q000097:blood
chemical_list: D014150:Antipsychotic Agents; C058272:norclozapine; D003024:Clozapine