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Pharmacopsychiatry 2015; 48(07): 286-291
DOI: 10.1055/s-0035-1565070
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Predicting Plasma Olanzapine Concentration Following a Change in Dosage: A Population Pharmacokinetic Study

T. Tsuboi
1   Department of Neuropsychiatry, Kyorin University School of Medicine, Tokyo, Japan
2   Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
,
R. R. Bies
3   Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN, USA
4   Indiana Clinical and Translational Sciences Institute, Indianapolis, IN, USA
5   Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, ON, Canada
,
T. Suzuki
2   Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
6   Department of Psychiatry, Inokashira Hospital, Tokyo, Japan
,
H. Takeuchi
2   Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
7   Complex Mental Health Division, Centre for Addiction and Mental Health, Toronto, ON, Canada
8   Department of Psychiatry, University of Toronto, Toronto, ON, Canada
,
S. Nakajima
2   Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
5   Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, ON, Canada
8   Department of Psychiatry, University of Toronto, Toronto, ON, Canada
9   Campbell Family Mental Health Research Institute, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
,
A. Graff-Guerrero
5   Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, ON, Canada
8   Department of Psychiatry, University of Toronto, Toronto, ON, Canada
9   Campbell Family Mental Health Research Institute, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
,
D. C. Mamo
5   Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, ON, Canada
8   Department of Psychiatry, University of Toronto, Toronto, ON, Canada
10   Department of Psychiatry, University of Malta, Valetta, Malta
,
F. Caravaggio
8   Department of Psychiatry, University of Toronto, Toronto, ON, Canada
9   Campbell Family Mental Health Research Institute, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
,
E. Plitman
8   Department of Psychiatry, University of Toronto, Toronto, ON, Canada
9   Campbell Family Mental Health Research Institute, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
,
M. Mimura
2   Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
,
B. G. Pollock
5   Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, ON, Canada
8   Department of Psychiatry, University of Toronto, Toronto, ON, Canada
,
H. Uchida
2   Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
5   Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, ON, Canada
› Author Affiliations
Further Information

Publication History

received 28 July 2015
revised 21 September 2015

accepted 28 September 2015

Publication Date:
27 October 2015 (online)

Also available at
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Abstract

Introduction: Due to high inter-individual variability in peripheral pharmacokinetic parameters, dosing of antipsychotics currently relies on clinical trial-and-error, and predicting antipsychotic plasma concentrations before changing a dose has been a challenge.

Methods: Patients with schizophrenia receiving a stable dose of olanzapine were included. 2 plasma samples were collected at 2 given time points for the measurement of plasma olanzapine concentrations. At least 7 days after a dosage change of olanzapine, a third sample was collected. The plasma concentration of the third sample was predicted in a blinded fashion using a mixed-effects model with NONMEM®, using the following information: the 2 baseline plasma concentrations, the interval between the last dose and blood draw, and clinical and demographic information.

Results: 31 subjects (mean±SD age=56.0±11.6; 19 men) were enrolled. The mean prediction (95% confidence interval) errors were 1.6 (−2.8 to 6.0) ng/mL. A highly significant correlation was observed between the observed and predicted concentrations of the third sample (r=0.91, p<0.001).

Discussion: Plasma olanzapine concentrations following an actual dosage change can be predicted in advance with a high degree of certainty.

Key words

olanzapine - plasma concentration - population pharmacokinetics - therapeutic drug monitoring
 

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