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 Bies

Research output: Contribution to journalArticle

107 Citations (Scopus)

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

Original languageEnglish (US)
Pages (from-to)157-165
Number of pages9
JournalJournal of Clinical Pharmacology
Volume48
Issue number2
DOIs
StatePublished - Feb 2008
Externally publishedYes

Fingerprint

olanzapine
Smoking
Antipsychotic Agents
Pharmaceutical Preparations
Population
Schizophrenia
Alzheimer Disease
Pharmacokinetics
Clinical Trials

Keywords

  • Alzheimer's disease
  • Antipsychotic
  • CATIE
  • Clinical antipsychotic trials of intervention effectiveness
  • Olanzapine
  • Pharmacokinetics
  • Schizophrenia

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Bigos, K. L., Pollock, B. G., Coley, K. C., Miller, D. D., Marder, S. R., Aravagiri, M., ... Bies, R. (2008). Sex, race, and smoking impact olanzapine exposure. Journal of Clinical Pharmacology, 48(2), 157-165. https://doi.org/10.1177/0091270007310385

Sex, race, and smoking impact olanzapine exposure. / Bigos, Kristin L.; Pollock, Bruce G.; Coley, Kim C.; Miller, Del D.; Marder, Stephen R.; Aravagiri, Manickam; Kirshner, Margaret A.; Schneider, Lon S.; Bies, Robert.

In: Journal of Clinical Pharmacology, Vol. 48, No. 2, 02.2008, p. 157-165.

Research output: Contribution to journalArticle

Bigos, KL, Pollock, BG, Coley, KC, Miller, DD, Marder, SR, Aravagiri, M, Kirshner, MA, Schneider, LS & Bies, R 2008, 'Sex, race, and smoking impact olanzapine exposure', Journal of Clinical Pharmacology, vol. 48, no. 2, pp. 157-165. https://doi.org/10.1177/0091270007310385
Bigos KL, Pollock BG, Coley KC, Miller DD, Marder SR, Aravagiri M et al. Sex, race, and smoking impact olanzapine exposure. Journal of Clinical Pharmacology. 2008 Feb;48(2):157-165. https://doi.org/10.1177/0091270007310385
Bigos, Kristin L. ; Pollock, Bruce G. ; Coley, Kim C. ; Miller, Del D. ; Marder, Stephen R. ; Aravagiri, Manickam ; Kirshner, Margaret A. ; Schneider, Lon S. ; Bies, Robert. / Sex, race, and smoking impact olanzapine exposure. In: Journal of Clinical Pharmacology. 2008 ; Vol. 48, No. 2. pp. 157-165.
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