<i>In vitro</i> evaluations for pharmacokinetic drug-drug interactions of a novel serotonin-dopamine activity modulator, brexpiprazole

Brexpiprazole, a serotonin-dopamine activity modulator, is indicated for the treatment of schizophrenia and also adjunctive therapy to antidepressants Major Depressive Disorder. To determine drug–drug interaction risk cytochrome P450, SLC ABC transporters, brexpiprazole its metabolite, DM-3411 were assessed in this vitro investigation.Brexpiprazole exhibited weak inhibitory effects (IC50 >13 μmol/L) on CYP2C9, CYP2C19, CYP2D6 CYP3A4 activities, but had moderate inhibitor CYP2B6 8.19 μmol/L). The ratio systemic unbound concentration (3.8 nmol/L) Ki value was sufficiently low. comparable potentials with only CYP3A4. mRNA expressions CYP1A2, not changed by exposure human hepatocytes.Brexpiprazole or no hepatic renal transporters (OATPs, OATs, OCTs, MATE1, BSEP), except MATE-2K (0.156 μmol/L DM-3411), even which (5.3 low.Brexpiprazole effected functions P-gp BCRP IC50 values 6.31 1.16 μmol/L, respectively, however, pharmacokinetic alteration observed clinical concomitant study substrates.These data suggest that unlikely cause clinically relevant drug interactions resulting from CYPs mediating absorption, metabolism, and/or disposition co-administered drugs.