Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Dec 1;46(6):828-836.
doi: 10.1097/FTD.0000000000001227. Epub 2024 Jun 3.

Therapeutic Drug Monitoring of Olanzapine: Effects of Clinical Factors on Plasma Concentrations in Psychiatric Patients

Nicolas Ansermot  1 , Harish Vathanarasa  1 , Setareh Ranjbar  2 , Mehdi Gholam  2 , Séverine Crettol  1 , Frederik Vandenberghe  1 , Franziska Gamma  3 , Kerstin Jessica Plessen  4 , Armin von Gunten  5 , Philippe Conus  6 , Chin B Eap  1   7   8   9
Affiliations

Therapeutic Drug Monitoring of Olanzapine: Effects of Clinical Factors on Plasma Concentrations in Psychiatric Patients

Nicolas Ansermot et al. Ther Drug Monit. .

Abstract

Background: Therapeutic drug monitoring (TDM) is strongly recommended for olanzapine due to its high pharmacokinetic variability. This study aimed to investigate the impact of various clinical factors on olanzapine plasma concentrations in patients with psychiatric disorders.

Methods: The study used TDM data from the PsyMetab cohort, including 547 daily dose-normalized, steady-state, olanzapine plasma concentrations (C:D ratios) from 248 patients. Both intrinsic factors (eg, sex, age, body weight) and extrinsic factors (eg, smoking status, comedications, hospitalization) were examined. Univariate and multivariable, linear, mixed-effects models were employed, with a stepwise selection procedure based on Akaike information criterion to identify the relevant covariates.

Results: In the multivariable model (based on 440 observations with a complete data set), several significant findings emerged. Olanzapine C:D ratios were significantly lower in smokers (β = -0.65, P < 0.001), valproate users (β = -0.53, P = 0.002), and inpatients (β = -0.20, P = 0.025). Furthermore, the C:D ratios decreased significantly as the time since the last dose increased (β = -0.040, P < 0.001). The male sex had a significant main effect on olanzapine C:D ratios (β = -2.80, P < 0.001), with significant interactions with age (β = 0.025, P < 0.001) and body weight (β = 0.017, P = 0.011). The selected covariates explained 30.3% of the variation in C:D ratios, with smoking status accounting for 7.7% and sex contributing 6.9%. The overall variation explained by both the fixed and random parts of the model was 67.4%. The model facilitated the prediction of olanzapine C:D ratios based on sex, age, and body weight.

Conclusions: The clinical factors examined in this study, including sex, age, body weight, smoking status, and valproate comedication, remarkably influence olanzapine C:D ratios. Considering these factors, in addition to TDM and the clinical situation, could be important for dose adjustment.

Keywords: clinical factors; olanzapine; plasma concentrations; therapeutic drug monitoring.

PubMed Disclaimer

Conflict of interest statement

Over the past 3 years, N. Ansermot has been awarded honoraria for a conference by Sysmex Suisse AG. S. Crettol has earned honoraria for conducting CME courses on behalf of Forum pour la formation médicale, Barr, Switzerland, and has provided consultancy services for the Swiss Health Observatory (Obsan) under the Swiss Federal Office of Public Health. F. Vandenberghe has received honoraria for delivering CME courses through Forum pour la formation médicale, Barr, Switzerland, in addition to CME courses for the Swiss Association of Public Health Administration and for a conference organized by Sysmex Suisse AG. C. B. Eap was honored with honoraria for his participation in conferences sponsored by Forum pour la formation médicale, Janssen-Cilag, Lundbeck, Otsuka, Sandoz, Servier, Sunovion, Sysmex Suisse AG, Takeda, Vifor-Pharma, and Zeller within the same time frame. No declarations were made by the remaining authors. The authors affirm no conflicts of interest concerning the content of this article.

Figures

FIGURE 1.
FIGURE 1.
Combined effects of sex and smoking status on daily dose–normalized olanzapine plasma concentrations (C:D ratios). The P-values are the results of the fitted linear mixed-effects models.
FIGURE 2.
FIGURE 2.
Interaction plots showing the marginal effects of age (A) and body weight (B) on daily dose–normalized olanzapine plasma concentrations (C:D ratios) using separate predicted data for male and female patients of different ages and body weights. The predictions were based on the multivariable analysis presented in Table 3 and adjusted for smokers, inpatients, nonvalproate users, and mean sampling time after the last dose of 14.2 hours.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. U.S. Food and Drug Administration. Drugs@FDA search. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed August 31, 2022.
    1. Huhn M, Nikolakopoulou A, Schneider-Thoma J, et al. Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis. Lancet. 2019;394:939–951. - PMC - PubMed
    1. Kantrowitz JT, Citrome L. Olanzapine: review of safety 2008. Expert Opin Drug Saf. 2008;7:761–769. - PubMed
    1. Callaghan JT, Bergstrom RF, Ptak LR, et al. . Olanzapine. Pharmacokinetic and pharmacodynamic profile. Clin Pharmacokinet. 1999;37:177–193. - PubMed
    1. Bhana N, Foster RH, Olney R, et al. . Olanzapine: an updated review of its use in the management of schizophrenia. Drugs. 2001;61:111–161. - PubMed

MeSH terms