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PHARMACOTHERAPY Volume 22, Number 11, 2002
manual for mental disorders, 4th ed. Washington, DC:
American Psychiatric Association, 1994:78–85.
to day. The availability of a once-daily dosage
form that allows for this flexibility in adminis-
tration is especially important for individuals,
primarily children, who may have difficulty
swallowing capsules.
In both studies, SLI381 was well tolerated.
The most common drug-related adverse events
2
3
. American Academy of Pediatrics. Clinical practice guideline:
diagnosis and evaluation of the child with attention-
deficit/hyperactivity disorder. Pediatrics 2000;105:1158–70.
. Barkley RA. Developmental course, adult outcome, and clinic-
referred ADHD adults. In: Barkley RA, ed. Attention-deficit
hyperactivity disorder: a handbook for diagnosis and treatment,
2
nd ed. New York: Guilford Press, 1998:186–224.
4
. Biederman J, Faraone S, Milberger S, et al. A prospective 4-
year follow-up study of attention-deficit hyperactivity and
related disorders. Arch Gen Psychiatry 1996;53:437–46.
5. Biederman J, Mick E, Faraone SV. Normalized functioning in
youths with persistent attention-deficit/hyperactivity disorder. J
Pediatr 1998;133:544–51.
(
insomnia, headache, nausea) were consistent
with frequently reported adverse events with
psychostimulant agents, were generally of mild
intensity, and quickly resolved. Although it
might be anticipated that more gastrointestinal
adverse events would be reported under fasted
conditions, the findings from study B
demonstrated that the fasted and sprinkled
conditions elicited comparable rates and types of
adverse events to the fed condition. Slight
increases in pulse and blood pressure were
clinically insignificant under all dosing
conditions.
6
. Swanson JM, McBurnnet K, Wigal T, et al. Effect of stimulant
medication on children with attention deficit disorder: a
“review of reviews.” Exceptional Children 1993;60:154–62.
7
. Spencer T, Biederman J, Wilens T, Harding M, O’Donnell D,
Griffin S. Pharmacotherapy of attention-deficit hyperactivity
disorder across the life cycle. J Am Acad Child Adolesc
Psychiatry 1996;35:409–32.
. Greenhill LL, Halperin JM, Abikoff H. Stimulant medications.
J Am Acad Child Adolesc Psychiatry 1999;38:503–12.
9. Solanto MV. Neuropsychopharmacological mechanisms of
stimulant drug action in attention-deficit hyperactivity
disorder: a review and integration. Behav Brain Res
8
1
998;94:127–52.
1
1
0. Kupietz SS, Bartlik B, Angrist B, Winsberg BG.
Psychostimulant plasma concentration and learning
performance. J Clin Psychopharmacol 1985;5:293–5.
1. Angrist B, Cor win J, Bartlik B, Cooper T. Early
pharmacokinetics and clinical effects of oral D-amphetamine in
normal subjects. Biol Psychiatry 1987;22:1357–68.
Summary
These studies document the pharmacokinetics
of SLI381 (Adderall XR) in healthy adult
volunteers. A dose of SLI381 20 mg closely
mimics the pharmacokinetics of immediate-
release Adderall 10 mg twice/day administered at
a 4-hour interval, and the two conditions were
bioequivalent with a similar safety profile. This
extended-release formulation of Adderall,
administered once/day in the morning, is
expected to elicit a similar time course of clinical
effect as the same total daily dose of immediate-
release Adderall given in two divided doses with
a 4-hour interval.
An important result was that the extent of
absorption of SLI381 was not significantly altered
after administration of a high-fat meal, allowing
patients the option of taking the capsule with or
without food. Finally, sprinkling the capsule
contents into applesauce was equivalent in the
rate and extent of absorption to taking the
capsule whole, with or without food, providing
further dosing flexibility for patients who have
difficulty swallowing capsules.
12. Brown GL, Hunt RD, Ebert MH, Bunney WE Jr, Kopin IJ.
Plasma levels of d-amphetamine in hyperactive children. Serial
behavior and motor responses. Psychopharmacology
1
979;62:133–40.
13. Brown GL, Ebert MH, Mikkelsen EJ, Hunt RD. Behavior and
motor activity response in hyperactive children and plasma
amphetamine levels following a sustained release preparation. J
Am Acad Child Psychiatry 1980;19:225–39.
14. Wilens TE, Spencer TJ. The stimulants revisited. Child
Adolesc Psychiatr Clin North Am 2000;9:573–603.
1
5. Swanson JM, Wigal S, Greenhill LL, et al. Analog classroom
assessment of Adderall in children with ADHD. J Am Acad
Child Adolesc Psychiatry 1998;37:519–26.
6. Pelham WE, Aronoff HR, Midlam JK, et al. A comparison of
Ritalin and Adderall: efficacy and time-course in children with
attention-deficit/hyperactivity disorder. Pediatrics
content/full/103/4/e43. Accessed March 20, 2002.
7. Pelham WE, Gnagy EM, Chronis AM, et al. A comparison of
morning-only and morning/late afternoon Adderall to morning-
only, twice-daily, and three times daily methylphenidate in
children with attention-deficit/hyperactivity disorder. Pediatrics
1
1
1
999;104:1300–11.
1
1
8. Manos MJ, Short EJ, Findling RL. Differential effectiveness of
methylphenidate and Adderall in school-age youths with
attention-deficit hyperactivity disorder. J Am Acad Child
Adolesc Psychiatry 1999;38:813–19.
9. Pliszka SR, Browne RG, Olvera RL, Wynne SK. A double-
blind, placebo-controlled study of Adderall and
methylphenidate in the treatment of attention-
deficit/hyperactivity disorder. J Am Acad Child Adolesc
Psychiatry 2000;39:619–26.
Acknowledgments
The authors thank Irving E. Weston, M.D. (MDS
Harris, Phoenix, AZ) for conducting the studies, and
Amy M. Horton, Pharm.D., for assisting in the
preparation of this manuscript.
2
0. Ahmann PA, Theye FW, Berg R, Linquist AJ, Van Erem AJ,
Campbell LR. Placebo-controlled evaluation of amphetamine
mixture-dextroamphetamine salts and amphetamine salts
(
Adderall): efficacy rate and side effects. Pediatrics
content/full/107/1/e10. Accessed March 20, 2002.
21. Spencer T, Biederman J, Wilens T, et al. Efficacy of a mixed
2
References
1
. American Psychiatric Association. Diagnostic and statistical