Pharmacokinetics of SLI381 (ADDERALL XR), an extended-release formulation of Adderall.
OBJECTIVE
To assess the pharmacokinetic (PK) properties of a single daily dose of Adderall (mixed amphetamine salts) and the extended-release formulation, SLI381 (ADDERALL XR), in pediatric attention-deficit/hyperactivity disorder (ADHD).


METHODS
Fifty-one children (aged 6-12 years) with ADHD participated in a 6-week, seven-visit, PK and pharmacodynamic study. PK sampling occurred during visit 1 and again at visit 7. At visit 1, subjects received an initial oral dose of SLI381, 20 mg. At visit 7 subjects completed 1 week of medication treatment following random assignment to once-daily orally dosed SLI381 10 mg, 20 mg, or 30 mg; Adderall 10 mg; or placebo.


RESULTS
PK parameters evidenced substantial intersubject variability (coefficients of variation = 28-56%). Time to maximum concentration (Tmax) for SLI381 versus Adderall showed average increases of 3.0 hours for dextroamphetamine (t = -2.35, p = .04, df = 8.6) and 3.2 hours for levoamphetamine (t = -2.39, p = .04, df = 9.2). The d- and l-isomer concentrations were highly correlated and approximated a 3:1 ratio.


CONCLUSIONS
SLI381 showed extended Tmax values compared with Adderall and appears suitable for once-daily dosing. Intersubject variability underscores the need for individual dose titration.
McGough
James J
JJ
Department of Psychiatry and Biobehavioral Sciences, Division of Child and Adolescent Psychiatry, UCLA Neuropsychiatric Institute, Los Angeles, USA. jmcgough@mednet.ucla.edu
Biederman
Joseph
J
Greenhill
Laurence L
LL
McCracken
James T
JT
Spencer
Thomas J
TJ
Posner
Kelly
K
Wigal
Sharon
S
Gornbein
Jeffrey
J
Tulloch
Simon
S
Swanson
James M
JM
D000662:Amphetamines / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D002648:Child; D016000:Cluster Analysis; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male
C090411:Adderall; D000662:Amphetamines; D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; C449521:SLI381