Pharmacokinetics and Safety of Brexpiprazole Following Multiple‐Dose Administration to Japanese Patients With Schizophrenia

Brexpiprazole is currently approved in the United States for the treatment of schizophrenia and as adjunctive treatment of major depressive disorder. In Canada, it is approved for the treatment of schizophrenia. This study evaluated the pharmacokinetics (PK) and safety of brexpiprazole in Japanese patients with schizophrenia. This phase 1 study comprised a 14‐day multiple‐dose administration of brexpiprazole 1, 4, and 6 mg/day (n = 7, 8, and 6, respectively). Plasma concentrations and PK parameters and the influence of CYP2D6 polymorphisms (intermediate metabolizers [IMs] and extensive metabolizers [EMs]) on PK were evaluated. Adverse events (AEs) were recorded. The C(max) and AUC(24h) of brexpiprazole and its metabolite, DM‐3411, showed dose‐proportionality. The C(max) and AUC(24h) of brexpiprazole showed accumulation of about 2.5‐ to 5.5‐fold on day 14, compared with those on day 1. The median t(max) and the mean elimination half‐life of brexpiprazole were 4–5 and 52–92 hours, respectively, across all doses on day 14. The C(24h) of brexpiprazole reached steady state after day 10 in all dose groups. The dose‐normalized C(max) and AUC(24h) of brexpiprazole on day 14 were higher in IM patients than in EM patients. AEs were generally mild to moderate, with transient serum prolactin increase being the most common event. No clinically significant changes were observed for other clinical laboratory values. Brexpiprazole was safe and well tolerated in the studied Japanese patients with schizophrenia.