期刊
JOURNAL OF CHILD NEUROLOGY
卷 26, 期 1, 页码 31-36出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/0883073810371981
关键词
atomoxetine; attention-deficit/hyperactivity disorder; ADHD; biomarkers; pharmacological; norepinephrine plasma membrane transport proteins; randomized controlled trial; sympathetic nervous system
资金
- Eli Lilly
- Jansen-Cilag
- Lilly, S.A., Alcobendas, Madrid, Spain
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-naive 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.
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