title: A non-randomized study to investigate the effects of the atypical antipsychotic aripiprazole on the steady-state pharmacokinetics of lamotrigine in patients with bipolar I disorder.
abstract: OBJECTIVE
  To determine the effect of aripiprazole on steady-state pharmacokinetics of lamotrigine in patients with bipolar I disorder who were clinically stable on lamotrigine (100-400 mg/day) for >or=4 weeks.
  
  
  METHODS
  In this open-label study, aripiprazole was administered at 10 mg/day for 3 days, 20 mg/day for 3 days, then 30 mg/day for 8 days. Blood samples were collected on Days -1 and 14 for determination of lamotrigine steady-state pharmacokinetic parameters. Safety and tolerability were assessed.
  
  
  RESULTS
  Eighteen patients were administered aripiprazole in combination with lamotrigine. Geometric mean (GM) values for lamotrigine maximum plasma concentration were similar for lamotrigine alone (26 ng/mL) and with co-administered aripiprazole (23 ng/mL). GM values for plasma lamotrigine area under the concentration-time curve (AUCtau) were comparable for lamotrigine alone (434 ng/h/mL) and with co-administered aripiprazole (394 ng/h/mL). Median T(max) of lamotrigine alone and combined with aripiprazole was 1.98 and 0.77 h, respectively. No changes to lamotrigine dose-normalized plasma trough concentrations were observed with co-administered aripiprazole. Sixteen patients (88.9%) experienced >or=1 adverse event (AE), the most common of which was insomnia (n = 6).
  
  
  CONCLUSIONS
  Aripiprazole had no meaningful effect on lamotrigine steady-state pharmacokinetics in patients with bipolar I disorder. No dosage adjustment of lamotrigine is required and the combination was generally safe and well tolerated.
authors.affiliation: Bristol-Myers Squibb, Princeton, New Jersey, USA.
authors.forename: Frank C
authors.initials: FC
authors.lastname: Schieber
authors.forename: David W
authors.initials: DW
authors.lastname: Boulton
authors.forename: Alfred H
authors.initials: AH
authors.lastname: Balch
authors.forename: Robert
authors.initials: R
authors.lastname: Croop
authors.forename: Suresh
authors.initials: S
authors.lastname: Mallikaarjun
authors.forename: Jeannine
authors.initials: J
authors.lastname: Benson
authors.forename: Berit X
authors.initials: BX
authors.lastname: Carlson
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D019540:Area Under Curve; D000068180:Aripiprazole; D001714:Bipolar Disorder / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D007319:Sleep Initiation and Maintenance Disorders / Q000139:chemically induced; D014227:Triazines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D000927:Anticonvulsants; D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D014227:Triazines; D000068180:Aripiprazole; D000077213:Lamotrigine