Pharmacokinetics of SLI381 (ADDERALL XR), an extended-release formulation of Adderall

by McGough JJ, Biederman J, Greenhill LL, McCracken JT,

Spencer TJ, Posner K, Wigal S, Gornbein J, Tulloch S, Swanson JM.
Department of Psychiatry and Biobehavioral Sciences, Division of Child and Adolescent Psychiatry,

UCLA Neuropsychiatric Institute, Los Angeles, USA.
[email protected]
J Am Acad Child Adolesc Psychiatry. 2003 Jun;42(6):684-91


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).

METHOD: 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.