Multiple daily-dose pharmacokinetics of lisdexamfetamine dimesylate in healthy adult volunteers

• Published in: Current medical research and opinion Vol. 24; no. 1; pp. 33 - 40
• Main Authors: Krishnan, Suma M., Stark, Jeffrey G.
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd 01.01.2008; Taylor & Francis; Informa Healthcare
• Subjects: Adult; Attention-deficit/hyperactivity disorder; Central Nervous System Stimulants - administration & dosage; Central Nervous System Stimulants - adverse effects; Central Nervous System Stimulants - pharmacokinetics; Dextroamphetamine; Dextroamphetamine - administration & dosage; Dextroamphetamine - adverse effects; Dextroamphetamine - blood; Dextroamphetamine - pharmacokinetics; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Health; Human Experimentation; Humans; Lisdexamfetamine Dimesylate; Male; Middle Aged; Pharmacokinetics; Prodrugs - administration & dosage; Prodrugs - adverse effects; Prodrugs - pharmacokinetics
• ISSN: 0300-7995; 1473-4877; 1473-4877
• DOI: 10.1185/030079908X242737

ABSTRACT Objective: To evaluate the pharmacokinetics of lisdexamfetamine dimesylate (LDX; Vyvanse*) in fasting healthy adult volunteers. Background: LDX is the first pro-drug stimulant and is indicated for the treatment of attention-deficit/hyperactivity disorder. LDX was developed with the goal of providing an extended effect that is consistent throughout the day, with a reduced potential for abuse, overdose toxicity, and drug tampering. Methods: This was an open-label, multiple-dose phase 1 study. LDX 70 mg/d was administered in the morning to 12 subjects for 7 days. Twenty blood samples were drawn during the study. Descriptive statistics were used for pharmacokinetic parameters. Results: Based on Cmin, steady-state d-amphetamine concentration (20.6 ng/mL) was reached by day 5, whereas LDX was undetectable, and 95% of the d-amphetamine was eliminated within 48 hours following the final dose on day 7. At steady state, d-amphetamine achieved a mean ± standard deviation Cmax of 90.1 ± 29.6 ng/mL, with a median Tmax of 3.0 hours. The AUC0-inf for d-amphetamine was 1453 ± 645.7 ng.h/mL.Complete elimination of the pro-drug occurred approximately 6 hours following the final dose on day 7. Adverse events were mild to moderate and similar to other oral amphetamines. Conclusions: This study describes the steady-state pharmacokinetics of LDX, a new pro-drug stimulant. Possible study limitations include an open-label design and a small sample size.