Influence of Itraconazole Co-administration and CYP2D6 Genotype on the Pharmacokinetics of the New Antipsychotic ARIPIPRAZOLE

For OPC-14857, the tmax in intermediate metabolizers was longer than that in extensive metabolizers, with the difference being amplified by co-administration of ITZ. The AUC336 hr showed similar increases by co-administration of ITZ in all genotypes. The urinary 6β-hydroxycortisol/cortisol concentration ratio following ITZ administration for 7 consecutive days was about half of that before the start of ITZ administration, indicating that CYP3A4 metabolic activity was inhibited by administration of ITZ. The influence of CYP3A4 inhibition on the pharmacokinetics of ARIPIPRAZOLE was not considered to be clinically significant. On the other hand, definite differences in pharmacokinetics were observed between CYP2D6 genotypes.