Pharmacokinetics of lisdexamfetamine dimesylate and its active metabolite, d-amphetamine, with increasing oral doses of lisdexamfetamine dimesylate in children with attention-deficit/hyperactivity disorder: a single-dose, randomized, open-label, crossover study

Abstract

Background: 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.

Objective: 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.

Methods: 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.

Results: 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 One child was withdrawn from the analysis because of pharyngitis considered to be unrelated to LDX use.

Conclusion: 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.