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

T. Tsuboi, R. R. Bies, T. Suzuki, H. Takeuchi, S. Nakajima, A. Graff-Guerrero, D. C. Mamo, F. Caravaggio, E. Plitman, M. Mimura, B. G. Pollock, H. Uchida

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)286-291
Number of pages6
Issue number7
Publication statusPublished - 2015 Oct 27


  • olanzapine
  • plasma concentration
  • population pharmacokinetics
  • therapeutic drug monitoring

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)


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