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 concentrat...

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Published inThe American journal of psychiatry Vol. 151; no. 1; p. 123
Main Authors Centorrino, F, Baldessarini, R J, Kando, J, Frankenburg, F R, Volpicelli, S A, Puopolo, P R, Flood, J G
Format Journal Article
LanguageEnglish
Published United States 01.01.1994
Subjects
Adult
Clozapine - analogs & derivatives
Clozapine - blood
Clozapine - metabolism
Clozapine - therapeutic use
Dose-Response Relationship, Drug
Drug Administration Schedule
Drug Therapy, Combination
Female
Fluoxetine - blood
Fluoxetine - pharmacology
Fluoxetine - therapeutic use
Humans
Male
Psychotic Disorders - blood
Psychotic Disorders - drug therapy
Schizophrenia - blood
Schizophrenia - drug therapy
Stimulation, Chemical
Valproic Acid - blood
Valproic Acid - pharmacology
Valproic Acid - therapeutic use
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Summary: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.
ISSN:0002-953X
DOI:10.1176/ajp.151.1.123