BACKGROUND: Brexpiprazole is a third-generation antipsychotic used for the treatment of schizophrenia or as an adjunctive drug for the treatment of affective and neurological disorders. The combined treatments with brexpiprazole and other drugs that are also cytochrome P450 (CYP) substrates may lead to pharmacokinetic drug-drug interactions. Our present work aimed to investigate the effects of prolonged administration of brexpiprazole on the expression of hepatic transcription factors and CYP drug-metabolizing enzymes. METHODS: Male Wistar rats received brexpiprazole (1 mg/kg ip.) for two weeks. Their livers were excised 24 h after the last dose, and the activities (HPLC), protein levels (Western blotting), and mRNAs (qRT-PCR) of CYP enzymes were measured. In parallel, the expression of hepatic transcription factors (Western blotting, qRT-PCR) and the concentration of serum hormones (ELISA) were assessed. RESULTS: serum levels. CONCLUSIONS: Brexpiprazole affects the expression of hepatic transcription factors and CYP, which may impact its own biotransformation and the metabolism of endogenous substances and concomitantly administered drugs, and lead to drug-drug interactions of pharmacological/clinical importance.
Danek et al. (Fri,) studied this question.