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

• Published in: Clinical therapeutics Vol. 32; no. 2; pp. 252 - 264
• Main Authors: Boellner, Samuel W., Stark, Jeffrey G., Krishnan, Suma, Zhang, Yuxin
• Format: Journal Article
• Language: English
• Published: Bridgewater, NJ EM Inc USA 01.02.2010; Elsevier; Elsevier Limited
• Subjects: ADHD; Administration, Oral; Adults; Amphetamines; Attention Deficit Disorder with Hyperactivity - drug therapy; Attention deficit hyperactivity disorder; Bioavailability; Biological and medical sciences; Biotransformation; Central Nervous System Stimulants - administration & dosage; Central Nervous System Stimulants - adverse effects; Central Nervous System Stimulants - pharmacokinetics; Child; Children & youth; Cross-Over Studies; Dextroamphetamine - administration & dosage; Dextroamphetamine - adverse effects; Dextroamphetamine - pharmacokinetics; Dose-Response Relationship, Drug; Drug dosages; Drug therapy; Female; Humans; Hyperactivity; Internal Medicine; LDX; Lisdexamfetamine Dimesylate; Male; Medical Education; Medical sciences; Pediatrics; Pharmaceuticals; Pharmacokinetics; Pharmacology. Drug treatments; Prodrugs - administration & dosage; Prodrugs - adverse effects; Prodrugs - pharmacokinetics; Psychiatry; stimulant; Teenagers; Treatment Outcome; Vyvanse; United States > US; Texas; pharmacokinetics; ADHD; LDX; stimulant; Vyvanse; Amphetamine derivatives; Human; CNS stimulant; Metabolite; Psychotropic; Single dose; Oral administration; Sympathomimetic; Lisdexamfetamine; Prodrug; Crossover study; Increasing dose; Randomization; Dexamfetamine; Attention disorder with hyperactivity; Pharmacokinetics; Child
• ISSN: 0149-2918; 1879-114X; 1879-114X
• DOI: 10.1016/j.clinthera.2010.02.011

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, ~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.