Serum concentrations of clozapine and its major metabolites: effects of cotreatment with fluoxetine or valproate.
Serum concentrations of clozapine, norclozapine, and clozapine-N-oxide were assayed in psychotic patients treated with clozapine alone (N = 17), clozapine with fluoxetine added (N = 6), or clozapine with valproic acid added (N = 11). Subjects were matched for age and other treatments, and concentrations were corrected for daily dose of clozapine (milligrams per kilogram of body weight). With valproic acid, there was a minor increase in total clozapine metabolites, which was even less with dose correction. Fluoxetine increased all clozapine analytes, in some cases to twice the levels in the subjects given only clozapine.
Centorrino
F
F
Department of Psychiatry, Harvard Medical School, Boston, MA.
Baldessarini
R J
RJ
Kando
J
J
Frankenburg
F R
FR
Volpicelli
S A
SA
Puopolo
P R
PR
Flood
J G
JG
D000328:Adult; D003024:Clozapine / Q000031:analogs & derivatives / Q000097:blood* / Q000378:metabolism / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005473:Fluoxetine / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D011618:Psychotic Disorders / Q000097:blood* / Q000188:drug therapy; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy; D013268:Stimulation, Chemical; D014635:Valproic Acid / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use
D005473:Fluoxetine; C058272:norclozapine; D014635:Valproic Acid; D003024:Clozapine