OBJECTIVE: This study was done to test the hypothesis that serum
concentration of norclozapine is a risk factor for leukopenia during
treatment with clozapine. METHOD: Maximum decreases in leukocyte counts in
44 unselected patients treated with clozapine were determined and then
correlated with drug doses and serum concentrations of clozapine,
norclozapine, and clozapine-N-oxide. RESULTS: White cell and granulocyte
counts decreased by up to 60%-73%, but there were no positive correlations
between these decrements and drug dose, drug level, ratio of drug level to
drug dose, or ratio of norclozapine level to clozapine level, nor were the
decreases related to age or gender. CONCLUSIONS: While these results do not
suggest in vivo hemotoxicity of norclozapine, further study of patients
with clinically significant leukopenia is required.
Abstract Teaser