lisdexamfetamine-dimesylate and Headache

The pharmacokinetics of lisdexamfetamine dimesylate, a long-acting prodrug stimulant, and its active moiety, d-amphetamine, including dose-proportionality and variability, were assessed in 20 healthy adults. Subjects received a single dose, sequentially, of 50, 100, 150, 200, and 250 mg of lisdexamfetamine dimesylate. Plasma lisdexamfetamine dimesylate and d-amphetamine were measured before dosing and 0.25 to 96 hours postdose. Dose-proportionality and intersubject and intrasubject variability of pharmacokinetic parameters were examined. Safety assessments included adverse events. All 20 subjects received 50 and 100 mg while 18, 12, and 9 subjects received 150, 200, and 250 mg of lisdexamfetamine dimesylate, respectively. Ten subjects were discontinued during the study for prespecified stopping rules (2 consecutive hourly readings of blood pressure: systolic >160 mm Hg or diastolic >100 mm Hg). Mean maximum observed plasma concentration (C(max)) and area under the concentration-time curve from time 0 to infinity (AUC(0-∞)) increased linearly and dose-dependently for d-amphetamine. Median time to C(max) ranged from 4 to 6 hours for d-amphetamine and 1.0 to 1.5 hours for lisdexamfetamine dimesylate. Intersubject and intrasubject variability over doses from 50 to 150 mg was low (<20%) for both C(max) and AUC(0-∞). Adverse events included nausea, dizziness, headache, psychomotor hyperactivity, and dysuria. These findings indicate that the pharmacokinetic parameters of d-amphetamine were dose-proportional and predictable over a wide range of lisdexamfetamine dimesylate doses.

Topics: Adult; Area Under Curve; Attention Deficit Disorder with Hyperactivity; Blood Pressure; Central Nervous System Stimulants; Dextroamphetamine; Dose-Response Relationship, Drug; Electrocardiography; Female; Headache; Humans; Lisdexamfetamine Dimesylate; Male; Middle Aged; Prodrugs; Pulse; Young Adult

Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Blood Pressure; Central Nervous System Stimulants; Dextroamphetamine; Double-Blind Method; Dyspnea; Female; Headache; Humans; Irritable Mood; Lisdexamfetamine Dimesylate; Male; Middle Aged; Sleep Initiation and Maintenance Disorders; Tachycardia; Treatment Outcome; Young Adult

Lisdexamfetamine dimesylate (LDX), a prodrug stimulant, is indicated for attention-deficit/hyperactivity disorder (ADHD) in children 6-12 years of age and in adults. In short-term studies, once-daily LDX provided efficacy throughout the day. This study presented here was conducted to assess the long-term safety, tolerability, and effectiveness of LDX in 6- to 12-year-olds with ADHD.. This open-label, multicenter, single-arm study enrolled children with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision criteria for ADHD. Following 1-week screening and washout periods, subjects were titrated to LDX 30, 50, or 70 mg/day over 4 weeks and placed on maintenance treatment for 11 months. The ADHD Rating Scale and Clinical Global Impression-Improvement scale measured effectiveness.. Of 272 subjects receiving LDX, 147 completed the study. Most adverse events were mild to moderate and occurred during the first 4 weeks. There were no clinically meaningful changes in blood pressure or electrocardiographic parameters. From baseline to endpoint, mean ADHD Rating Scale scores improved by 27.2 points (P<.0001). Improvements occurred during each of the first 4 weeks, and were maintained throughout. Based on Clinical Global Impression-Improvement scale scores, >80% of subjects at endpoint and >95% of completers at 12 months were rated "improved.". Long-term 30, 50, and 70 mg/day LDX was generally well tolerated and effective in children with ADHD.

Topics: Administration, Oral; Appetite; Attention Deficit Disorder with Hyperactivity; Child; Dextroamphetamine; Diagnostic and Statistical Manual of Mental Disorders; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Headache; Humans; Lisdexamfetamine Dimesylate; Male; Psychiatric Status Rating Scales; Sleep Initiation and Maintenance Disorders; Time Factors; Treatment Outcome; Weight Loss

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.

Topics: Administration, Oral; Adult; Area Under Curve; Biological Availability; Blood Pressure; Capsules; Cross-Over Studies; Dextroamphetamine; Eating; Fasting; Female; Flushing; Food-Drug Interactions; Half-Life; Headache; Humans; Hyperkinesis; Lisdexamfetamine Dimesylate; Lysine; Male; Metabolic Clearance Rate; Molecular Structure; Tachycardia