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Title: Predicting plasma olanzapine concentration following a change in dosage : a population pharmacokinetic study
Authors: Tsuboi, Takashi
Bies, Robert R.
Suzuki, Takefumi
Takeuchi, Hiroyoshi
Nakajima, Shinichiro
Graff-Guerrero, Ariel
Mamo, David
Caravaggio, Fernando
Plitman, Eric
Mimura, Masaru
Pollock, Bruce G.
Uchida, Hiroyuki
Keywords: Olanzapine
Drug monitoring
Issue Date: 2015
Publisher: Georg Thieme Verlag
Citation: Tsuboi, T., Bies, R. R., Suzuki, T., Takeuchi, H., Nakajima, S., Graff-Guerrero, A., ... & Pollock, B. G. (2015). Predicting plasma olanzapine concentration following a change in dosage: a population pharmacokinetic study. Pharmacopsychiatry, 48(07), 286-291.
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.
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