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Exposure-Response Analysis for Aripiprazole Once-Monthly in Patients Diagnosed With Bipolar I Disorder
Xiaofeng Wang1, Luann Phillips2, Matthew Harlin3
1Pharmacometrics, Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, NJ, USA.
Clinical Pharmacology in Drug Development
|August 22, 2025
Summary
Aripiprazole once-monthly maintenance therapy for bipolar I disorder lowers recurrence risk with higher drug exposure. A concentration of 95 ng/mL is linked to a significant reduction in mood episode recurrence.
Area of Science:
- Pharmacology
- Psychiatry
- Clinical Pharmacy
Background:
- Aripiprazole once-monthly (AOM) is indicated for bipolar I disorder (BP-I) maintenance monotherapy.
- Understanding the relationship between drug exposure and treatment outcomes is crucial for optimizing therapy.
Purpose of the Study:
- To validate a population pharmacokinetic model for AOM in BP-I patients.
- To develop an exposure-response model to assess the impact of aripiprazole exposure on mood episode recurrence in BP-I.
Main Methods:
- Validated a population pharmacokinetic model using BP-I patient data.
- Generated aripiprazole exposure data for an exposure-response model.
- Utilized continuous and categorical models to analyze recurrence risk.
Main Results:
- Higher aripiprazole exposure was associated with a reduced risk of mood episode recurrence.
- Each 1 ng/mL increase in plasma concentration decreased recurrence hazard by 0.34%.
- A plasma concentration of 95 ng/mL significantly predicted time to recurrence, reducing risk by 36%.
Conclusions:
- Plasma aripiprazole concentration is a key predictor of recurrence in BP-I patients on AOM.
- Maintenance therapy with AOM is important for preventing mood episodes.
- A 95 ng/mL threshold is relevant for BP-I, demonstrating a smaller effect size than in schizophrenia.
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