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

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 ?M*h in EM2s to 5.8 ± 1.7 ?M*h, 16.3 ± 2.9 ?M*h, and 50.2 ± 7.3 ?M*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.

SUBMITTER: Brown JT

PROVIDER: S-EPMC4862932 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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

Brown J T JT Abdel-Rahman S M SM van Haandel L L Gaedigk A A Lin Y S YS Leeder J S JS

Clinical pharmacology and therapeutics 20160112 6

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). Pla ...[more]

PMID: 26660002

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Dataset Information

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

Publications

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

Similar Datasets

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