Relation of Blood Counts during Clozapine Treatment to Serum Concentrations of Clozapine and Nor-Clozapine

OBJECTIVE: To determine the relation between serum clozapine and nor-clozapine levels and blood cell counts during clozapine treatment. METHOD: We undertook a prospective longitudinal study of 37 consecutive patients with a diagnosis of schizophrenia treated with clozapine. We obtained informed consent and then determined serum concentrations of clozapine and nor-clozapine weekly. Clozapine was administered daily in divided doses given every 12 hours and adjusted according to clinical guidelines for its use. Samples for serum concentrations were taken at steady state, immediately before the next morning's dose, for 4 to 8 weeks. Complete blood counts (CBC), weight, and vital signs (that is, blood pressure, pulse, and temperature) were also monitored weekly before the morning's dose of clozapine was administered. RESULTS: Analyses of variance showed no significant changes over the 8-week treatment course in the observed mean white blood count (WBC), red blood count (RBC), neutrophils, and lymphocytes counts, or in the hemoglobin and hematocrit. Only a few weak correlations (r < 0.21) were found between these hematological parameters and the measures of serum clozapine and nor-clozapine. CONCLUSIONS: The mechanism of clozapine-induced hematotoxicity at the therapeutic dosage range is probably not by direct toxicity of clozapine or nor-clozapine to the blood cells or their precursors. The formation of the cytotoxic nitrenium compound from clozapine by neutrophils may be necessary.