title: Relative bioavailability of lisdexamfetamine 70-mg capsules in fasted and fed healthy adult volunteers and in solution: a single-dose, crossover pharmacokinetic study.
abstract: The relative bioavailability of oral lisdexamfetamine dimesylate, a prodrug of d-amphetamine, and active d-amphetamine was assessed in an open-label, single-dose, 3-treatment, 3-period, randomized, crossover study in 18 healthy adult volunteers. Following a fast of at least 10 hours, subjects were administered an intact capsule of 70 mg lisdexamfetamine, a solution containing the capsule contents, or an intact capsule with a high-fat meal. Standard meals started 4 hours following lisdexamfetamine administration. Blood samples were taken predose (0 hours) and 0.5 to 72 hours postdose, and the concentrations of d-amphetamine and lisdexamfetamine were measured. AUC and C(max) for d-amphetamine were similar when lisdexamfetamine 70 mg was administered to healthy adults in the fed or fasted state. The AUC of intact lisdexamfetamine was similar when the latter was taken without food or in solution, but C(max) was lower when lisdexamfetamine was administered with food. The t(max) of d-amphetamine and intact lisdexamfetamine was similar when taken in solution or in the fasted state but was about 1 hour longer when taken with food. Adverse events were typical for amphetamine products. These findings indicate that food does not have a significant effect on d-amphetamine or lisdexamfetamine bioavailability in healthy adults and that lisdexamfetamine was well tolerated.
authors.affiliation: New River Pharmaceuticals Inc., 3 W Shore Rd, Belvedere, CA 94920, USA. sumakrishnan@gmail.com
authors.forename: Suma
authors.initials: S
authors.lastname: Krishnan
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D002214:Capsules; D018592:Cross-Over Studies; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D004435:Eating / Q000502:physiology*; D005215:Fasting / Q000502:physiology*; D005260:Female; D005483:Flushing / Q000139:chemically induced; D018565:Food-Drug Interactions; D006207:Half-Life; D006261:Headache / Q000139:chemically induced; D006801:Humans; D006948:Hyperkinesis / Q000139:chemically induced; D000069478:Lisdexamfetamine Dimesylate; D008239:Lysine / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D015394:Molecular Structure; D013610:Tachycardia / Q000139:chemically induced
chemical_list: D002214:Capsules; D008239:Lysine; D000069478:Lisdexamfetamine Dimesylate; D003913:Dextroamphetamine