N-desmethylclozapine, an insensitive marker of clozapine-induced agranulocytosis and granulocytopenia.

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.