title: Sex, race, and smoking impact olanzapine exposure.
abstract: Response to antipsychotics is highly variable, which may be due in part to differences in drug exposure. The goal of this study was to evaluate the magnitude and variability of concentration exposure of olanzapine. Patients with Alzheimer's disease (n = 117) and schizophrenia (n = 406) were treated with olanzapine as part of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). Combined, these patients (n = 523) provided 1527 plasma samples for determination of olanzapine concentrations. Nonlinear mixed-effects modeling was used to determine the population pharmacokinetics of olanzapine, and patient-specific covariates were evaluated as potential contributors to variability in drug exposure. The population mean olanzapine clearance and volume of distribution were 16.1 L/h and 2150 L, respectively. Elimination of olanzapine varied nearly 10-fold (range, 6.66-67.96 L/h). Smoking status, sex, and race accounted for 26%, 12%, and 7% of the variability, respectively (P < .0001). Smokers cleared olanzapine 55% faster than non/past smokers (P < .0001). Men cleared olanzapine 38% faster than women (P < .0001). Patients who identified themselves as black or African American cleared olanzapine 26% faster than other races (P < .0001). Differences in olanzapine exposure due to sex, race, and smoking may account for some of the variability in response to olanzapine.
authors.affiliation: Department of Pharmaceutical Sciences, University of Pittsburgh, School of Pharmacy, 805 Salk Hall, 3501 Terrace St, Pittsburgh, PA 15261, USA.
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Bigos
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Pollock
authors.forename: Kim C
authors.initials: KC
authors.lastname: Coley
authors.forename: Del D
authors.initials: DD
authors.lastname: Miller
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Marder
authors.forename: Manickam
authors.initials: M
authors.lastname: Aravagiri
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Kirshner
authors.forename: Lon S
authors.initials: LS
authors.lastname: Schneider
authors.forename: Robert R
authors.initials: RR
authors.lastname: Bies
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000706:statistics & numerical data; D000465:Algorithms; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000208:ethnology / Q000378:metabolism; D014150:Antipsychotic Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D044466:Asian People / Q000706:statistics & numerical data; D001569:Benzodiazepines / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D007198:Indians, North American / Q000706:statistics & numerical data; D008297:Male; D008657:Metabolic Clearance Rate; D015999:Multivariate Analysis; D000077152:Olanzapine; D012559:Schizophrenia / Q000188:drug therapy* / Q000208:ethnology / Q000378:metabolism; D012737:Sex Factors; D012907:Smoking; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution; D016896:Treatment Outcome; D044465:White People / Q000706:statistics & numerical data
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D000077152:Olanzapine