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Clin Pharmacol Ther. 2016 Jun;99(6):642-50. doi: 10.1002/cpt.319. Epub 2016 Jan 12.

Single dose, CYP2D6 genotype-stratified pharmacokinetic study of atomoxetine in children with ADHD.

Author information

1
Department of Pharmacy Practice and Pharmaceutical Sciences, University of Minnesota College of Pharmacy, Duluth, Minnesota, USA.
2
Division of Clinical Pharmacology, Toxicology, and Therapeutic Innovation, Department of Pediatrics, Children's Mercy Kansas City and University of Missouri-Kansas City, Kansas City, Missouri, USA.
3
Department of Pharmaceutics, University of Washington School of Pharmacy, Seattle, Washington, USA.

Abstract

The effect of CYP2D6 genotype on the dose-exposure relationship for atomoxetine has not been well characterized in children. Children 6-17 years of age diagnosed with attention-deficit hyperactivity disorder (ADHD) were stratified by CYP2D6 genotype into groups with 0 (poor metabolizers [PMs], n = 4), 0.5 (intermediate metabolizers [IMs], n = 3), one (extensive metabolizer [EM]1, n = 8) or two (EM2, n = 8) functional alleles and administered a single 0.5 mg/kg oral dose of atomoxetine (ATX). Plasma and urine samples were collected for 24 (IM, EM1, and EM2) or 72 hours (PMs). Dose-corrected ATX systemic exposure (area under the curve [AUC]0-∞ ) varied 29.6-fold across the study cohort, ranging from 4.4 ± 2.7 μM*h in EM2s to 5.8 ± 1.7 μM*h, 16.3 ± 2.9 μM*h, and 50.2 ± 7.3 μM*h in EM1s, IMs, and PMs, respectively (P < 0.0001). Simulated steady state profiles at the maximum US Food and Drug Administration (FDA)-recommended dose suggest that most patients are unlikely to attain adequate ATX exposures. These data support the need for individualized dosing strategies for more effective use of the medication.

PMID:
26660002
PMCID:
PMC4862932
DOI:
10.1002/cpt.319
[Indexed for MEDLINE]
Free PMC Article

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