CYP2D6 metabolizer status and atomoxetine dosing in children and adolescents with ADHD.
To determine whether physicians can adequately titrate atomoxetine without knowing genotype status for hepatic cytochrome P450 2D6, we pooled data from two open-label studies of atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder. Patients were assessed weekly up to 10 weeks and doses titrated for efficacy and tolerability at the discretion of investigators (max. 1.8 mg/kg/d). Mean dose was 0.1 mg/kg/d lower in poor metabolizer (PM) patients (n=87) than extensive metabolizers (EMs, n=1239). PMs demonstrated marginally better efficacy on the ADHDRS-IV-Parent:Inv and had comparable safety profiles, except for a 4.0-bpm greater increase in mean pulse rate and a 1.0-kg greater weight loss. Changes from baseline in Fridericia QTc did not differ between groups or correlate with dose in PMs. Results suggest genotyping is unnecessary during routine clinical management, because investigators were able to dose atomoxetine to comparable efficacy and safety levels in EMs and PMs without knowledge of genotype metabolizer status.
Trzepacz
Paula T
PT
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA. ptt@lilly.com
Williams
David W
DW
Feldman
Peter D
PD
Wrishko
Rebecca E
RE
Witcher
Jennifer W
JW
Buitelaar
Jan K
JK
D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D002648:Child; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D008297:Male; D011437:Propylamines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013997:Time Factors
D018759:Adrenergic Uptake Inhibitors; D011437:Propylamines; D000069445:Atomoxetine Hydrochloride; D019389:Cytochrome P-450 CYP2D6