Evaluation of Potential Pharmacokinetic Drug-Drug Interaction between Armodafinil and Aripiprazole in Healthy Adults.
INTRODUCTION
Armodafinil, a moderate inducer of cytochrome P450 (CYP) 3A4, has been studied as adjunctive therapy to maintenance medications for major depressive episodes associated with bipolar I disorder. We evaluated the effect of daily dosing with armodafinil on the pharmacokinetics and safety of the CYP3A4 substrate aripiprazole, an atypical antipsychotic used to treat bipolar I disorder.


METHODS
Healthy adults received 15 mg aripiprazole alone and after armodafinil (250 mg/day) pretreatment. Pharmacokinetic parameters were derived from plasma concentrations of aripiprazole and its active metabolite, dehydro-aripiprazole, obtained over 16 days after each aripiprazole administration. Steady-state pharmacokinetics of armodafinil and its 2 circulating metabolites was assessed.


RESULTS
Of 36 subjects enrolled, 24 were evaluable for pharmacokinetic analysis. Armodafinil reduced systemic exposure to aripiprazole (Cmax, - 8%; AUC0-∞, -34%) and dehydro-aripiprazole, which is both formed and eliminated in part via CYP3A4 (Cmax, - 10%; AUC0-∞, - 32%). Adverse events were generally consistent with known safety profiles of each agent.


DISCUSSION
Systemic exposure to aripiprazole and dehydro-aripiprazole was moderately reduced following armodafinil pretreatment. The combination was generally well tolerated under the conditions studied.