Relation of leukocyte counts during clozapine treatment to serum concentrations of clozapine and metabolites.
OBJECTIVE
This study was done to test the hypothesis that serum concentration of norclozapine is a risk factor for leukopenia during treatment with clozapine.


METHODS
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.
Centorrino
F
F
Department of Psychiatry, Harvard Medical School, Boston, MA.
Baldessarini
R J
RJ
Flood
J G
JG
Kando
J C
JC
Frankenburg
F R
FR
D003024:Clozapine / Q000031:analogs & derivatives* / Q000097:blood* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007958:Leukocyte Count; D007970:Leukopenia / Q000097:blood / Q000139:chemically induced* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011618:Psychotic Disorders / Q000097:blood / Q000188:drug therapy*; D012307:Risk Factors
C058272:norclozapine; D003024:Clozapine; C079149:clozapine N-oxide