Single- and Multiple-Dose Pharmacokinetics of an Oral Mixed Amphetamine Salts Extended-Release Formulation in Adults

OBJECTIVES: 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. FINDINGS: 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. CONCLUSION: 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.