SLI381 (Adderall XR), a two-component, extended-release formulation of mixed amphetamine salts: bioavailability of three test formulations and comparison of fasted, fed, and sprinkled administration.
OBJECTIVE
To assess the bioavailability of three test formulations of a single dose of extended-release Adderall 20-mg capsules compared with two doses of immediate-release Adderall 10-mg tablets, and to assess the bioequivalence of a single 30-mg dose of the chosen extended-release Adderall formulation (designated as SLI381) administered in applesauce (sprinkled) and the same dose administered as an intact capsule with or without food.


METHODS
Randomized, open-label, crossover study.


METHODS
Clinical research unit.


METHODS
Forty-one healthy adults.


METHODS
Study A had four treatment sequences: three test formulations (A, B, and C) of a single dose of extended-release Adderall 20 mg, and two 10-mg doses of Adderall given 4 hours apart. Study B had three treatment sequences: a single dose of SLI381 30 mg as an intact capsule after overnight fast, an intact capsule after a high-fat breakfast, and the contents of a capsule sprinkled in 1 tablespoon of applesauce.


RESULTS
The 20-mg test formulation A had comparable pharmacokinetic profiles and bioequivalence in rate and extent of drug absorption to Adderall 10 mg twice/day for both d- and l-amphetamine. Formulations B and C had statistically significant differences from the reference drug in some pharmacokinetic parameters. A 30-mg dose of SLI381 showed no significant differences in rate and extent of absorption of d- and l-amphetamine for fasted or sprinkled conditions compared with the high-fat meal condition.


CONCLUSIONS
SLI381 20 mg/day is bioequivalent to Adderall 10 mg twice/day. SLI381 30 mg administered in applesauce is bioequivalent in terms of both rate and extent of absorption to the same dose administered as an intact capsule in both fasted and fed states.
Tulloch
Simon J
SJ
Department of Clinical Research, Shire Pharmaceutical Development Inc., Rockville, Maryland 20850-1801, USA.
Zhang
Yuxin
Y
McLean
Angus
A
Wolf
Kathleen N
KN
D000328:Adult; D000661:Amphetamine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000662:Amphetamines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000704:Analysis of Variance; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D016001:Confidence Intervals; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D004041:Dietary Fats / Q000378:metabolism*; D005215:Fasting / Q000378:metabolism*; D005260:Female; D018565:Food-Drug Interactions / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged
D000662:Amphetamines; D003692:Delayed-Action Preparations; D004041:Dietary Fats; C449521:SLI381; D000661:Amphetamine