title: Evaluation of Potential Pharmacokinetic Drug-Drug Interaction between Armodafinil and Aripiprazole in Healthy Adults.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  Systemic exposure to aripiprazole and dehydro-aripiprazole was moderately reduced following armodafinil pretreatment. The combination was generally well tolerated under the conditions studied.
authors.affiliation: Sci-Med Bridge, Malvern, Pennsylvania, USA.
authors.forename: M
authors.initials: M
authors.lastname: Darwish
authors.affiliation: Teva Pharmaceuticals, Inc, Frazer, Pennsylvania, USA.
authors.forename: M
authors.initials: M
authors.lastname: Bond
authors.affiliation: Teva Pharmaceuticals, Inc, Frazer, Pennsylvania, USA.
authors.forename: R
authors.initials: R
authors.lastname: Yang
authors.affiliation: Teva Pharmaceuticals, Inc, West Chester, Pennsylvania, USA.
authors.forename: E T
authors.initials: ET
authors.lastname: Hellriegel
authors.affiliation: Teva Pharmaceuticals, Inc, West Chester, Pennsylvania, USA.
authors.forename: P
authors.initials: P
authors.lastname: Robertson
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D000068180:Aripiprazole / Q000009:adverse effects / Q000493:pharmacokinetics*; D001559:Benzhydryl Compounds / Q000009:adverse effects / Q000494:pharmacology*; D065701:Cytochrome P-450 CYP3A Inducers / Q000009:adverse effects / Q000494:pharmacology*; D003865:Major Depressive Disorder / Q000188:drug therapy; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D010879:Piperazines / Q000378:metabolism; D015363:Quinolones / Q000378:metabolism; D064690:Wakefulness-Promoting Agents / Q000009:adverse effects / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D001559:Benzhydryl Compounds; D065701:Cytochrome P-450 CYP3A Inducers; D010879:Piperazines; D015363:Quinolones; D064690:Wakefulness-Promoting Agents; C517414:dehydroaripiprazole; D000068180:Aripiprazole; D000077408:Modafinil