Atomoxetine pharmacokinetics in children and adolescents with attention deficit hyperactivity disorder

J Child Adolesc Psychopharmacol. Spring 2003;13(1):53-63. doi: 10.1089/104454603321666199.

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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / pharmacokinetics*
  • Antidepressive Agents / therapeutic use
  • Area Under Curve
  • Atomoxetine Hydrochloride
  • Attention Deficit Disorder with Hyperactivity / blood*
  • Attention Deficit Disorder with Hyperactivity / drug therapy
  • Child
  • Cytochrome P-450 CYP2D6 / genetics
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Propylamines / administration & dosage
  • Propylamines / pharmacokinetics*
  • Propylamines / therapeutic use
  • Treatment Outcome

Substances

  • Antidepressive Agents
  • Propylamines
  • Atomoxetine Hydrochloride
  • Cytochrome P-450 CYP2D6