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, multipledose 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.