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

Authors :
Ishigooka, Jun
Iwashita, Shuichi
Higashi, Koushi
Liew, Ei Leen
Tadori, Yoshihiro
Source :
Journal of Clinical Pharmacology. Jan2018, Vol. 58 Issue 1, p74-80. 7p.
Publication Year :
2018

Abstract

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 Cmax and AUC24h of brexpiprazole and its metabolite, DM-3411, showed dose-proportionality. The Cmax and AUC24h of brexpiprazole showed accumulation of about 2.5- to 5.5-fold on day 14, compared with those on day 1. The median tmax and the mean elimination half-life of brexpiprazole were 4-5 and 52-92 hours, respectively, across all doses on day 14. The C24h of brexpiprazole reached steady state after day 10 in all dose groups. The dose-normalized Cmax and AUC24h 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00912700
Volume :
58
Issue :
1
Database :
Academic Search Index
Journal :
Journal of Clinical Pharmacology
Publication Type :
Academic Journal
Accession number :
126749126
Full Text :
https://doi.org/10.1002/jcph.979