TY - JOUR
T1 - Predicting Plasma Olanzapine Concentration Following a Change in Dosage
T2 - A Population Pharmacokinetic Study
AU - Tsuboi, T.
AU - Bies, R. R.
AU - Suzuki, T.
AU - Takeuchi, H.
AU - Nakajima, S.
AU - Graff-Guerrero, A.
AU - Mamo, D. C.
AU - Caravaggio, F.
AU - Plitman, E.
AU - Mimura, M.
AU - Pollock, B. G.
AU - Uchida, H.
N1 - Publisher Copyright:
© Georg Thieme Verlag KG Stuttgart New York.
PY - 2015/10/27
Y1 - 2015/10/27
N2 - 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.
AB - 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.
KW - olanzapine
KW - plasma concentration
KW - population pharmacokinetics
KW - therapeutic drug monitoring
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U2 - 10.1055/s-0035-1565070
DO - 10.1055/s-0035-1565070
M3 - Article
C2 - 26506574
AN - SCOPUS:84948105798
SN - 0176-3679
VL - 48
SP - 286
EP - 291
JO - Pharmakopsychiatrie und Neuropsychopharmakologie
JF - Pharmakopsychiatrie und Neuropsychopharmakologie
IS - 7
ER -
