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: Jennifer W Witcher, Amanda Long, Brian Smith, John-Michael Sauer, John Heilgenstein, Timothy Wilens, Thomas Spencer, Joseph Biederman
• Journal: Journal of child and adolescent psychopharmacology (J Child Adolesc Psychopharmacol) Vol. 13 Issue 1 Pg. 53-63 ( 2003) ISSN: 1044-5463 [Print] United States
• PMID: 12804126 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

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