Multiple daily-dose pharmacokinetics of lisdexamfetamine dimesylate in healthy adult volunteers.
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.
Krishnan
Suma M
SM
New River Pharmaceuticals, Radford, VA, USA. sumamkrishnan@gmail.com
Stark
Jeffrey G
JG
D000328:Adult; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D003913:Dextroamphetamine / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006262:Health; D006805:Human Experimentation; D006801:Humans; D000069478:Lisdexamfetamine Dimesylate; D008297:Male; D008875:Middle Aged; D011355:Prodrugs / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics
D000697:Central Nervous System Stimulants; D011355:Prodrugs; D000069478:Lisdexamfetamine Dimesylate; D003913:Dextroamphetamine