Sex, race, and smoking impact olanzapine exposure

Kristin L Bigos; Bruce G Pollock; Kim C Coley; Del D Miller; Stephen R Marder; Manickam Aravagiri; Margaret A Kirshner; Lon S Schneider; Robert R Bies

doi:10.1177/0091270007310385

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Sex, race, and smoking impact olanzapine exposure

Journal article

Peer reviewed

Sex, race, and smoking impact olanzapine exposure

Kristin L Bigos, Bruce G Pollock, Kim C Coley, Del D Miller, Stephen R Marder, Manickam Aravagiri, Margaret A Kirshner, Lon S Schneider and Robert R Bies

Journal of clinical pharmacology, Vol.48(2), pp.157-165

02/2008

DOI: 10.1177/0091270007310385

PMID: 18199892

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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.

Multivariate Analysis

Benzodiazepines - blood

Schizophrenia - metabolism

Antipsychotic Agents - blood

Humans

Male

Metabolic Clearance Rate

Indians, North American - statistics & numerical data

Tissue Distribution

Tandem Mass Spectrometry

Antipsychotic Agents - therapeutic use

Chromatography, Liquid

Adult

Female

Administration, Oral

Alzheimer Disease - drug therapy

European Continental Ancestry Group - statistics & numerical data

Treatment Outcome

Benzodiazepines - pharmacokinetics

Antipsychotic Agents - pharmacokinetics

African Americans - statistics & numerical data

Schizophrenia - ethnology

Algorithms

Adolescent

Alzheimer Disease - ethnology

Alzheimer Disease - metabolism

Sex Factors

Schizophrenia - drug therapy

Asian Continental Ancestry Group - statistics & numerical data

Benzodiazepines - therapeutic use

Smoking

Details

Title: Subtitle: Sex, race, and smoking impact olanzapine exposure
Creators: Kristin L Bigos - Department of Pharmaceutical Sciences, University of Pittsburgh, School of Pharmacy, 805 Salk Hall, 3501 Terrace St, Pittsburgh, PA 15261, USA
Bruce G Pollock
Kim C Coley
Del D Miller
Stephen R Marder
Manickam Aravagiri
Margaret A Kirshner
Lon S Schneider
Robert R Bies
Resource Type: Journal article
Publication Details: Journal of clinical pharmacology, Vol.48(2), pp.157-165
Publisher: England
DOI: 10.1177/0091270007310385
PMID: 18199892
ISSN: 0091-2700
eISSN: 1552-4604
Grant note: MH065416 / NIMH NIH HHS MH064173 / NIMH NIH HHS NH076420 / NIH HHS
Language: English
Date published: 02/2008
Academic Unit: Psychiatry
Record Identifier: 9984004191502771

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