Changes of urine dihydroxyphenylglycol to norepinephrine ratio in children with attention-deficit hyperactivity disorder (ADHD) treated with atomoxetine.
This study investigated changes in the urine dihydroxyphenylglycol to norepinephrine ratio in patients with attention-deficit hyperactivity disorder (ADHD) treated with atomoxetine. The possible relationship with clinical response was also explored. Newly ADHD diagnosed, treatment-naïve children or adolescents were double-blindly randomized (2:1) to atomoxetine (n = 28) or placebo (n = 13). The dihydroxyphenylglycol to norepinephrine ratio decreased in both groups, showing significantly greater changes with atomoxetine than with placebo at week 6 (-42% versus -14%; P = .001), when dosed at 1.2 mg/kg/day, than at week 2 (-20% versus -2%; P = .118) with a dose of 0.5 mg/kg/day. Although the significant dihydroxyphenylglycol to norepinephrine ratio decrease with atomoxetine indicated norepinephrine transporter blockade, no association with ADHD clinical response (ADHD Rating Scale-IV-Parent:Investigator) was found. Therefore, dihydroxyphenylglycol to norepinephrine ratio might be a useful pharmacodynamic/pharmacokinetic biomarker, although not sufficiently sensitive to predict clinical efficacy. It remains a possibility that this ratio might have value to facilitate personalized atomoxetine pharmacotherapy in ADHD patients.
Montoya
Alonso
A
Lilly Research Laboratories, Madrid, Spain. montoya_alonso@lilly.com
Escobar
Rodrigo
R
García-Polavieja
María J
MJ
Lachno
D Richard
DR
Alda
José Ángel
JÁ
Artigas
Josep
J
Cardo
Esther
E
García
Marta
M
Gastaminza
Xavier
X
Gilaberte
Inmaculada
I
D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use*; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000652:urine*; D002648:Child; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000652:urine; D009638:Norepinephrine / Q000652:urine*; D010865:Pilot Projects; D011437:Propylamines / Q000627:therapeutic use*; D016896:Treatment Outcome
D018759:Adrenergic Uptake Inhibitors; D011437:Propylamines; D008734:Methoxyhydroxyphenylglycol; D000069445:Atomoxetine Hydrochloride; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine