Boellner Samuel W, Pennick Michael, Fiske Kimberly, Lyne Andrew, Shojaei Amir
Clinical Study Centers, Little Rock, Arkansas, USA.
Pharmacotherapy. 2007 Sep;27(9):1253-62. doi: 10.1592/phco.27.9.1253.
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).
Phase I-II, open-label, dose-escalation study.
Clinical study center.
Fourteen children (aged 6-12 yrs) and 14 adolescents (aged 13-17 yrs) with ADHD.
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.
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 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.
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.
评估用于诊断为注意力缺陷多动障碍（ADHD）的儿童和青少年的胍法辛口服缓释制剂的单剂量和多剂量药代动力学。
I-II期、开放标签、剂量递增研究。
临床研究中心。
14名患有ADHD的儿童（6至12岁）和14名青少年（13至17岁）。
所有患者在第1天接受2毫克胍法辛单剂量给药。他们在第9至15天接受每日2毫克剂量，第16至22天接受3毫克剂量，第23至29天接受4毫克剂量。
在第1天给药前以及24小时内每隔一段时间采集血样、生命体征和心电图（ECG），并在第14天和28天重复测量。胍法辛呈现线性药代动力学。儿童和青少年的平均血浆浓度、峰浓度（C(max)）以及总暴露量或24小时暴露量（分别为浓度-时间曲线下面积AUC或AUC(0-24)）如下：单次2毫克剂量后，儿童的AUC(0-无穷大)为65.2±23.9纳克·小时/毫升，青少年为47.3±13.7纳克·小时/毫升，C(max)分别为2.55±1.03纳克/毫升和1.69±0.43纳克/毫升；多次2毫克剂量后，儿童的AUC(0-24)为70.0±28.3纳克·小时/毫升，青少年为48.2±16.1纳克·小时/毫升，C(max)分别为4.39±1.66纳克/毫升和2.86±0.77纳克/毫升；多次4毫克剂量后，儿童的AUC(0-24)为162±116纳克·小时/毫升，青少年为(117±28.4纳克·小时/毫升，C(max)分别为10.1±7.09纳克/毫升和7.01±1.53纳克/毫升。单次2毫克剂量后，儿童的半衰期为14.4±2.39小时，青少年为17.@9±5.77小时。最常见的治疗中出现的不良事件为嗜睡、失眠、头痛、视力模糊和情绪改变。大多数为轻度至中度严重程度，最高发生率与4毫克剂量相关。血压、脉搏和心电图读数均在正常范围内。
胍法辛缓释制剂呈现线性药代动力学。儿童的血浆浓度和与浓度相关的药代动力学参数高于青少年。这些差异可能是由于青少年和年轻男性受试者体重较重所致。未报告严重不良事件。
