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Event Related Potentials ERPs and other EEG Based Methods for Extracting Biomarkers of Brain Dysfunction: Examples from Pediatric Attention Deficit/Hyperactivity Disorder ADHD
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Single dose, CYP2D6 genotype-stratified pharmacokinetic study of atomoxetine in children with ADHD

J T Brown1, S M Abdel-Rahman2, L van Haandel2

  • 1Department of Pharmacy Practice and Pharmaceutical Sciences, University of Minnesota College of Pharmacy, Duluth, Minnesota, USA.

Clinical Pharmacology and Therapeutics
|December 15, 2015
PubMed

Insights

CYP2D6 genotype significantly impacts atomoxetine exposure in children with ADHD. Genetic variations affect how children metabolize atomoxetine, necessitating personalized dosing for effective treatment.

Area of Science:

  • Pharmacogenomics
  • Pediatric Pharmacology

Background:

  • The pharmacokinetics of atomoxetine, particularly the dose-exposure relationship in pediatric populations, require further elucidation.
  • CYP2D6 genotype is known to influence drug metabolism, but its specific impact on atomoxetine exposure in children with ADHD is not well-defined.

Purpose of the Study:

  • To investigate the effect of CYP2D6 genotype on atomoxetine pharmacokinetics in children diagnosed with attention-deficit hyperactivity disorder (ADHD).
  • To assess the variability in atomoxetine systemic exposure across different CYP2D6 metabolic groups in pediatric patients.

Main Methods:

  • Children aged 6-17 with ADHD were stratified into CYP2D6 poor, intermediate, and extensive metabolizer groups.
  • A single oral dose of atomoxetine (0.5 mg/kg) was administered, and plasma/urine samples were collected for pharmacokinetic analysis.
  • Area under the curve (AUC0-∞) was calculated to determine dose-corrected systemic exposure.

Main Results:

  • Dose-corrected atomoxetine exposure (AUC0-∞) showed a 29.6-fold variation across the cohort.
  • Significant differences in exposure were observed between CYP2D6 genotype groups, with poor metabolizers exhibiting the highest exposure (50.2 ± 7.3 μM*h).
  • Simulations indicated that most patients may not achieve adequate atomoxetine exposure at the maximum FDA-recommended dose.

Conclusions:

  • CYP2D6 genotype is a critical determinant of atomoxetine dose-exposure relationships in children with ADHD.
  • The substantial inter-individual variability in exposure highlights the need for individualized dosing strategies.
  • Personalized atomoxetine dosing based on CYP2D6 genotype may improve treatment efficacy in pediatric ADHD management.

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