title: Large intraindividual variability of olanzapine serum concentrations in adolescent patients.
abstract: Olanzapine (OLZ) is a widely used antipsychotic substance. Therapeutic drug monitoring (TDM) of OLZ is recommended but is based on known reference ranges derived from intraindividual and interindividual variability measurements. There have been few studies on the interindividual variability of OLZ serum concentrations in adolescents, and no data on intraindividual variability are available. This study explored the intraindividual variability of OLZ serum concentrations in 85 patients attending a child and adolescent psychiatric hospital (age at first assessment: mean +/- SD, 16.7 +/- 2.0; range, 10.3-20.6 years; 54 male, 31 female). A total of 577 steady-state OLZ serum concentrations (2 to 24 measurements per patient; mean, 6.8, and SD, +/-5.4) were measured, using high-performance liquid chromatography (HPLC). Intraindividual variability of dose-corrected OLZ serum concentrations was 1.04- to 10.7-fold. The intraindividual variabilities of the metabolites OLZ N-desmethyl (DMO) and OLZ 2-hydroxymethyl (2OH) were 1.08- to 83.2-fold and 1.0- to 47-fold, respectively. Intraindividual variability of OLZ (DMO; 2OH) serum concentration accounted for 47% (89.8%, 74.9%) of total variance. OLZ daily dose, number of co-medications, body mass index (BMI), age, and post-dose interval had a significant influence on the intraindividual variability of dose-corrected OLZ serum concentrations (all P < 0.001). The serum concentrations of OLZ and OLZ metabolites in adolescents show high intraindividual variability, potentially limiting the value of TDM. It is recommended that repeated serum concentration measurements are made in individuals treated with OLZ, in order to obtain a more precise estimate of the intraindividual variability of serum concentrations.
authors.affiliation: Department of Child and Adolescent Psychiatry, University Hospital Marburg and Giessen, Campus Marburg, Germany. cbachman@med.uni-marburg.de
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Bachmann
authors.forename: Michael
authors.initials: M
authors.lastname: Haberhausen
authors.forename: Monika
authors.initials: M
authors.lastname: Heinzel-Gutenbrunner
authors.forename: Helmut
authors.initials: H
authors.lastname: Remschmidt
authors.forename: Frank M
authors.initials: FM
authors.lastname: Theisen
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001569:Benzodiazepines / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002648:Child; D002851:Chromatography, High Pressure Liquid; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D008297:Male; D000077152:Olanzapine; D012559:Schizophrenia / Q000188:drug therapy
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D000077152:Olanzapine