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

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 C_min, 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 C_max of 90.1 ± 29.6 ng/mL, with a median T_max of 3.0 hours. The AUC_0–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.

Key words: :

• Attention-deficit/hyperactivity disorder
• Dextroamphetamine
• Lisdexamfetamine dimesylate
• Pharmacokinetics