Single- and multiple-dose pharmacokinetics of an oral mixed amphetamine salts extended-release formulation in adults.
OBJECTIVE
Assess the bioavailability of mixed amphetamine salts extended-release (MAS XR) 30-mg capsules and the dose proportionality of pharmacokinetic measures for MAS XR 20, 40, and 60 mg.


METHODS
Study A, an open-label single-period study, and Study B, a randomized, open-label, three-way crossover study, were conducted in healthy adults in a clinical research unit. In Study A, 20 subjects received a single MAS XR 30-mg capsule by mouth daily for 7 days. In Study B, 12 subjects received single oral doses of MAS XR 20, 40, and 60 mg separated by 7-14-day washout periods.


RESULTS
Plasma dextroamphetamine (d-amphetamine) and levoamphetamine (l-amphetamine) concentrations were measured using a validated LC-MS/MS method. In Study A, a 3:1 ratio of d-amphetamine to l-amphetamine was observed for AUC0-inf and Cmax. Tmax was 4.2 and 4.3 hours for d-amphetamine to l-amphetamine, respectively. In Study B, for d- and l-amphetamine, statistically significant differences were observed for AUC0-t, AUC0-inf, and Cmax between all doses; there was a linear relationship between pharmacokinetic variables and dose and Tmax was similar for each isomer (range: 4.5-5.3 hours) with all given MAS XR doses.


CONCLUSIONS
The extent of exposure as assessed by mean AUC0-24 and Cmax reflected the 3:1 ratio of d-amphetamine to l-amphetamine in MAS XR 30-mg capsules. The pharmacokinetic profiles of MAS XR 20, 40, and 60 mg are dose proportional for the isomers.
Clausen
Susan B
SB
Shire Pharmaceutical Inc., Wayne, PA 19087, USA.
Read
Stephanie C
SC
Tulloch
Simon J
SJ
D000284:Administration, Oral; D000328:Adult; D000662:Amphetamines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001289:Attention Deficit Disorder with Hyperactivity / Q000097:blood* / Q000188:drug therapy; D001682:Biological Availability; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D003913:Dextroamphetamine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D013237:Stereoisomerism
D000662:Amphetamines; D003692:Delayed-Action Preparations; D003913:Dextroamphetamine