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.
Author(s): Boellner SW, Stark JG, Krishnan S, Zhang Y.
Affiliation(s): Clinical Study Centers, Little Rock, Arkansas, USA. swboellner@suddenlink.net
Publication date & source: 2010, Clin Ther. , 32(2):252-64
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 One child was withdrawn from the analysis because of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.
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