Model Answers publishes reference ranges to support optimal dosing of aripiprazole, olanzapine, and quetiapine. This work complements both references ranges for risperidone, paliperidone ( and the publication of an online tool to aid interpretation


Background Schizophrenia is a common disease which is commonly managed using antipsychotic medications (APS). Inadequate response and lack of adherence often prevent optimal therapeutic effectiveness. Monitoring APS concentrations can be useful to help improve outcomes for the patient.
Aims The aim of this study was to develop Breference ranges^ for oral aripiprazole, olanzapine, and quetiapine to allow clinicians to understand expected variability in patients treated with APS. The reference ranges were constructed to account for different oral doses, sampling times, and variability both between, and within, subjects.

Methods Population pharmacokinetic models were used to simulate plasma concentrations over time under different doses and population demographics. The references were validated against external data both numerically and graphically.
Results Reference ranges for oral aripiprazole, olanzapine, and quetiapine were derived and successfully validated against the external data. The 80% reference range for aripiprazole following a 2-mg oral dose was 14.7–41.6 ng/mL 0–4 h post dose and 10.6–37.1 ng/mL 20–24 h post dose. These ranges increased to 221–624 ng/mL 0–4 h post dose following administration of a 30- mg dose, and 159–557 ng/mL 20–24 h post dose. The 80% reference range 0–4 h post dose was 22.5–67.1 ng/mL following a 15- mg dose once daily of oral olanzapine, and 179–768 ng/mL following a 150-mg dose once daily of oral quetiapine.

Conclusions Comparing individual patients’ APS levels with reference ranges, along with a full clinical assessment, could provide important insights to help a clinician optimize APS therapy.

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