title: Pharmacokinetics and pharmacodynamics of guanfacine extended release in adolescents aged 13-17 years with attention-deficit/hyperactivity disorder.
abstract: The safety and efficacy of guanfacine extended release (up to 4 mg/day) for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents aged 6-17 years is well documented. Data suggest that weight-adjusted doses of guanfacine extended release >0.08 mg/kg but ≤0.12 mg/kg, if tolerated, may provide additional clinical benefits. For many adolescents, such dosing would exceed 4 mg/day, the highest approved dose. This open-label multicenter study evaluated the safety, tolerability, and steady-state pharmacokinetics of guanfacine extended release at escalated forced doses ≤9 mg/day in adolescents (N = 31) aged 13-17 years with ADHD. Following doses of approximately 0.12 mg/kg, the highest weight group (>70-90 kg) exhibited lower mean clearance at steady-state than the lowest weight group (≥30-50 kg). Consistent with its known antihypertensive effects, guanfacine extended release was associated with dose-dependent decreases in blood pressure (BP) and heart rate (HR). The physiologic response of increased BP upon standing was blunted in a dose-related manner while the physiologic response of increased HR upon standing was not substantively affected. The most common treatment-emergent adverse events were somnolence, dizziness, and sinus bradycardia. These results, and those from prior studies, support further examination of the efficacy and safety of higher weight-adjusted doses of guanfacine extended release for ADHD.
authors.affiliation: Shire Development LLC, Wayne, PA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Martin
authors.affiliation: Independent Consultant in Cardiac Safety, Wellington, FL.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Satin
authors.affiliation: Vince and Associates Clinical Research, Overland Park, KS.
authors.forename: Bradley D
authors.initials: BD
authors.lastname: Vince
authors.affiliation: Miami Children's Hospital, Miami, FL.
authors.forename: Americo F
authors.initials: AF
authors.lastname: Padilla
authors.affiliation: Shire Pharmaceutical Development Ltd, Basingstoke, United Kingdom.
authors.forename: Carla
authors.initials: C
authors.lastname: White
authors.affiliation: Shire Development LLC, Wayne, PA.
authors.forename: Mary
authors.initials: M
authors.lastname: Corcoran
authors.affiliation: Shire Development LLC, Wayne, PA.
authors.forename: Annette
authors.initials: A
authors.lastname: Stevenson
authors.affiliation: Shire Development LLC, Wayne, PA.
authors.forename: James
authors.initials: J
authors.lastname: Ermer
mesh_terms: D000293:Adolescent; D000294:Adolescent Behavior / Q000187:drug effects*; D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D000367:Age Factors; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D001794:Blood Pressure / Q000187:drug effects; D003692:Delayed-Action Preparations; D005260:Female; D005431:Florida; D016316:Guanfacine / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D016896:Treatment Outcome
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D003692:Delayed-Action Preparations; D016316:Guanfacine
keywords: pediatrics; pharmaceutical medicine; pharmacodynamics; pharmacokinetics and drug metabolism; psychopharmacology