Population pharmacokinetic analysis and exposure–response analysis of brexpiprazole in Japanese patients with agitation in Alzheimer’s dementia

This study evaluated the use of population pharmacokinetic (PopPK) and exposure–response (ER) modeling to assess whether dose adjustments of brexpiprazole are needed in Japanese patients experiencing agitation associated with Alzheimer’s dementia.

Researchers applied a previously developed PopPK model to clinical data from Japanese patients with Alzheimer’s dementia to characterize brexpiprazole exposure and evaluate the influence of age and renal function. The validated model was then used to support an exposure–response analysis examining the relationship between drug exposure and improvements in agitation symptoms.

The analysis found that advancing age and reduced renal function were associated with increased brexpiprazole exposure. However, these increases were generally within the plateau region of the exposure–response relationship, suggesting limited additional impact on efficacy.

The findings suggest that dose adjustments based on the evaluated patient characteristics may not be necessary in this population. The authors note that additional investigation may be warranted given the limited data and remaining uncertainty in the exposure–response model.

This research illustrates how population pharmacokinetic and exposure–response modeling can help characterize patient variability, evaluate dose adjustment considerations, and inform evidence-based dosing decisions in clinical development.