Clinical Study Centers, Little Rock, Arkansas, USA.
Clin Ther. 2010 Feb;32(2):252-64. doi: 10.1016/j.clinthera.2010.02.011.
Lisdexamfetamine dimesylate (LDX) is a long-acting oral prodrug stimulant indicated for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children 6 to 12 years old and in adults. Information on the pharmacokinetic profile of LDX in children with ADHD is lacking.
The aim of this study was to assess the pharmacokinetic properties of d-amphetamine delivery from LDX, and intact LDX with increasing doses of LDX administered in children with ADHD.
This single-dose, randomized, open-label, 3-period crossover study was conducted in children aged 6 to 12 years with ADHD symptoms that adversely affected school performance and required a medication switch. Eligible patients had prior stimulant experience, with good tolerability. Patients were administered a single oral dose of LDX 30, 50, or 70 mg in a randomized sequence. Each study period was separated by a 6-day washout. The pharmacokinetic properties of d-amphetamine and intact LDX were calculated over 48 hours. Adverse events (AEs) were assessed using physical examination, including vital sign measurements, and ECG.
The study enrolled 18 children (mean [SD] age, 9.6 [1.9] years [range, 6-12 years]; 56% boys; weight, 36.0 [7.6] kg; 44% white, 44% black). Mean (%CV) C(max) values of d-amphetamine postdose were 53.2 (18.1), 93.3 (19.5), and 134.0 (19.4) ng/mL with LDX 30, 50, and 70 mg, respectively (T(max), approximately 3.5 hours). These findings suggest that the overall AUC for d-amphetamine was dose proportional. The intact LDX AUC was 10% to 20% higher in girls than in boys, and for d-amphetamine was <10% higher. The most commonly reported AEs, of 17 total cases, with 30-, 50-, and 70-mg LDX were anorexia (4 [22%], 7 [41%], and 8 [47%], respectively), elevated blood pressure (2 [11%], 1 [6%], and 3 [18%]), and abdominal pain (2 [11%], 2 [12%], and 2 [12%]). All AEs were mild or moderate. No serious AEs were reported. One child was withdrawn from the analysis because of pharyngitis considered to be unrelated to LDX use.
The findings from this study in a small, select population of children with ADHD suggest that the concentrations of d-amphetamine, the active metabolite of LDX, after single-dose administration of LDX at increasing doses appeared to be dose proportional and had low interpatient variability.
Lisdexamfetamine dimesylate（LDX）是一种长效口服前药兴奋剂，适用于治疗 6 至 12 岁儿童和成人的注意力缺陷/多动障碍（ADHD）。目前缺乏 LDX 在 ADHD 儿童中的药代动力学特征信息。
本研究旨在评估 ADHD 儿童中 LDX 给药后 d-苯丙胺的药代动力学特征和完整 LDX 的药代动力学特征，这些儿童的剂量递增。
这是一项单剂量、随机、开放标签、3 期交叉研究，纳入了年龄在 6 至 12 岁之间的 ADHD 症状儿童，这些症状对学业表现有不利影响，需要药物转换。合格的患者有过兴奋剂治疗经验，且耐受性良好。患者以随机顺序接受 LDX 30、50 或 70mg 的单次口服剂量。每个研究期之间间隔 6 天洗脱期。在 48 小时内计算 d-苯丙胺和完整 LDX 的药代动力学特征。使用体格检查（包括生命体征测量和心电图）评估不良事件（AE）。
该研究纳入了 18 名儿童（平均[标准差]年龄，9.6[1.9]岁[范围，6-12 岁]；56%为男孩；体重，36.0[7.6]kg；44%为白人，44%为黑人）。d-苯丙胺的 C（max）值分别为 LDX 30、50 和 70mg 后 53.2（18.1）、93.3（19.5）和 134.0（19.4）ng/mL（T（max），约 3.5 小时）。这些发现表明 d-苯丙胺的总体 AUC 呈剂量比例关系。女孩的完整 LDX AUC 比男孩高 10%至 20%，而 d-苯丙胺则高 <10%。17 例总病例中最常见的报告 AEs 有厌食症（4[22%]、7[41%]和 8[47%]，分别用 LDX 30、50 和 70mg）、血压升高（2[11%]、1[6%]和 3[18%]）和腹痛（2[11%]、2[12%]和 2[12%]）。所有 AEs 均为轻度或中度。未报告严重 AEs。1 名儿童因考虑与 LDX 使用无关的咽炎而退出分析。
这项在 ADHD 儿童小样本、选择人群中的研究结果表明，在递增剂量的 LDX 单次给药后，LDX 活性代谢物 d-苯丙胺的浓度似乎呈剂量比例关系，且个体间变异性较低。
