Pharmacokinetics of a guanfacine extended-release formulation in children and adolescents with attention-deficit-hyperactivity disorder

Pharmacotherapy. 2007 Sep;27(9):1253-62. doi: 10.1592/phco.27.9.1253.


Study objective: To evaluate the single- and multiple-dose pharmacokinetics of an oral extended-release formulation of guanfacine in children and adolescents with a diagnosis of attention-deficit-hyperactivity disorder (ADHD).

Design: Phase I-II, open-label, dose-escalation study.

Setting: Clinical study center.

Patients: Fourteen children (aged 6-12 yrs) and 14 adolescents (aged 13-17 yrs) with ADHD.

Intervention: All patients received guanfacine as a single 2-mg dose on day 1. They received a daily dose of 2 mg on days 9-15, 3 mg on days 16-22, and 4 mg on days 23-29.

Measurements and main results: Blood samples, vital signs, and electrocardiograms (ECGs) were obtained before dosing on day 1 and at intervals over 24 hours, with repeat measurements on days 14 and 28. Guanfacine demonstrated linear pharmacokinetics. Mean plasma concentrations, peak exposure (C(max)), and total or 24-hour exposure (area under the concentration-time curve [AUC](0-infinity) or AUC(0-24), respectively) were as follows in children and adolescents, respectively: after a single 2-mg dose, AUC(0-infinity) was 65.2 +/- 23.9 ng x hour/ml and 47.3 +/- 13.7 ng x hour/ml and C(max) was 2.55 +/- 1.03 ng x ml and 1.69 +/- 0.43 ng/ml after multiple 2-mg doses, AUC(0-24) was 70.0 +/- 28.3 ng x hour/ml and 48.2 +/- 16.1 ng x hour/ml and C(max) was 4.39 +/- 1.66 ng/ml and 2.86 +/- 0.77 ng/ml; and after multiple 4-mg doses, AUC(0-24) was 162 +/- 116 ng x hour/ml and 117 +/- 28.4 ng x hour/ml and C(max) was 10.1 +/- 7.09 ng/ml and 7.01 +/- 1.53 ng/ml. After a single 2-mg dose, half-life was 14.4 +/- 2.39 hours in children and 17.9 +/- 5.77 hours in adolescents. The most frequent treatment-emergent adverse events were somnolence, insomnia, headache, blurred vision, and altered mood. Most were mild to moderate in severity, with the highest frequency associated with the 4-mg doses. Blood pressure, pulse, and ECG reading.hour/ml s were all within normal limits.

Conclusion: Guanfacine extended-release formulation demonstrated linear pharmacokinetics. Plasma concentrations and concentration-related pharmacokinetic parameters were higher in children than in adolescents. These differences are likely due to heavier body weights in adolescents and young male subjects. No serious adverse events were reported.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenergic alpha-Agonists / administration & dosage
  • Adrenergic alpha-Agonists / adverse effects
  • Adrenergic alpha-Agonists / pharmacokinetics*
  • Age Factors
  • Area Under Curve
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Blood Pressure / drug effects
  • Body Weight
  • Child
  • Delayed-Action Preparations
  • Dose-Response Relationship, Drug
  • Electrocardiography
  • Female
  • Guanfacine / administration & dosage
  • Guanfacine / adverse effects
  • Guanfacine / pharmacokinetics*
  • Half-Life
  • Heart Rate / drug effects
  • Humans
  • Male
  • Sex Factors
  • Tissue Distribution


  • Adrenergic alpha-Agonists
  • Delayed-Action Preparations
  • Guanfacine