title: Atomoxetine pharmacokinetics in children and adolescents with attention deficit hyperactivity disorder.
abstract: OBJECTIVE
  Atomoxetine is indicated for the treatment of attention deficit hyperactivity disorder in children, adolescents, and adults. This study was conducted, in part, to evaluate the single-dose and steady-state pharmacokinetics of atomoxetine in pediatric patients.
  
  
  METHODS
  This was an open-label, dose-titration study in pediatric patients with attention deficit hyperactivity disorder. Eligible patients could elect to participate in a single-dose or steady-state discontinuation pharmacokinetic evaluation including serial plasma sample collection over 24 hours. Plasma concentrations of atomoxetine, 4-hydroxyatomoxetine, and N-desmethylatomoxetine were determined using an atmospheric pressure chemical ionization liquid chromatography/mass spectrometry/mass spectrometry assay. Pharmacokinetic parameters were calculated using noncompartmental analysis.
  
  
  RESULTS
  Twenty-one cytochrome P450 2D6 extensive metabolizer patients participated in these single-dose and steady-state pharmacokinetic evaluations. Atomoxetine was rapidly absorbed, with peak plasma concentrations occurring 1 to 2 hours after dosing. Half-life averaged 3.12 and 3.28 hours after a single dose and at steady state, respectively. Minimal accumulation occurred in plasma after multiple twice-daily dosing in extensive metabolizer pediatric patients, as expected based on single-dose pharmacokinetics. As the dose (in mg/kg) increased, proportional increases in area under the curve were observed.
  
  
  CONCLUSIONS
  The pharmacokinetics of atomoxetine in extensive metabolizer patients were well characterized over a wide range of doses in this study. Atomoxetine pharmacokinetics in pediatric patients and adult subjects were similar after adjustment for body weight.
authors.affiliation: Eli Lilly and Company, Lilly Research Laboratories, Corporate Center, Indianapolis, IN 46285, USA. jwitcher@lilly.com
authors.forename: Jennifer W
authors.initials: JW
authors.lastname: Witcher
authors.forename: Amanda
authors.initials: A
authors.lastname: Long
authors.forename: Brian
authors.initials: B
authors.lastname: Smith
authors.forename: John-Michael
authors.initials: JM
authors.lastname: Sauer
authors.forename: John
authors.initials: J
authors.lastname: Heilgenstein
authors.forename: Timothy
authors.initials: T
authors.lastname: Wilens
authors.forename: Thomas
authors.initials: T
authors.lastname: Spencer
authors.forename: Joseph
authors.initials: J
authors.lastname: Biederman
mesh_terms: D000293:Adolescent; D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000097:blood* / Q000188:drug therapy; D002648:Child; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D011437:Propylamines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D011437:Propylamines; D000069445:Atomoxetine Hydrochloride; D019389:Cytochrome P-450 CYP2D6