Vyvanse Half-Life Curves Across Various Strengths
Pharmacokinetic Profile of Lisdexamfetamine (Vyvanse)
Vyvanse exhibits a two-phase elimination pattern: the prodrug lisdexamfetamine has an extremely short half-life of less than 1 hour, while its active metabolite d-amphetamine has a half-life of approximately 8.6-11.3 hours, with these parameters remaining consistent across all available strengths (20mg, 30mg, 40mg, 50mg, 60mg, 70mg). 1, 2
Prodrug (Lisdexamfetamine) Pharmacokinetics
- Lisdexamfetamine reaches peak plasma concentration (Tmax) at approximately 1 hour after oral administration 1, 2
- The elimination half-life of lisdexamfetamine averages less than 1 hour (specifically 0.5 hours) in patients ages 6 years and older 1, 2
- Plasma concentrations of unconverted lisdexamfetamine become non-quantifiable by 8 hours after administration 1
- The prodrug is rapidly hydrolyzed in the blood by red blood cells to d-amphetamine and l-lysine, with negligible levels remaining at 6 hours post-dose 1, 2
Active Metabolite (d-Amphetamine) Pharmacokinetics
- D-amphetamine reaches peak plasma concentration (Tmax) at approximately 3.5-4.4 hours after Vyvanse administration 1, 3, 2
- The elimination half-life of d-amphetamine is 8.6-9.5 hours in pediatric patients (ages 6-12 years) and 10-11.3 hours in healthy adults 1, 2
- D-amphetamine levels peak approximately 3 hours later than lisdexamfetamine levels and persist throughout the day 2
- Clinical effects of d-amphetamine from Vyvanse have been shown to persist up to 14 hours 2
Dose-Independent Pharmacokinetics
- Vyvanse demonstrates linear pharmacokinetics across the therapeutic dose range: 30-70mg in pediatric patients (ages 6-12 years) and 50-250mg in adults 1
- Weight/dose normalized AUC and Cmax values are equivalent across all strengths in both pediatric and adult populations 1
- There is no accumulation of lisdexamfetamine or d-amphetamine at steady state, with low inter-subject variability (<25%) and intra-subject variability (<8%) 1
Comparative Pharmacokinetic Curves: Vyvanse vs Immediate-Release Amphetamine
- Compared to immediate-release d-amphetamine, Vyvanse produces an identical total exposure (AUC) but with a 50% lower peak concentration (Cmax) and significantly delayed time to peak (Tmax delayed by approximately 1.1 hours) 3, 4
- The lag time for plasma amphetamine increase is 0.6 hours longer with Vyvanse compared to immediate-release d-amphetamine 3
- Vyvanse produces smaller but more sustained increases in striatal dopamine compared to immediate-release d-amphetamine at equivalent doses 4
Clinical Implications of the Half-Life Profile
- The prolonged d-amphetamine half-life (10-11.3 hours in adults) explains the once-daily dosing regimen for all Vyvanse strengths 1, 2
- The rapid conversion of prodrug to active metabolite with sustained release characteristics provides therapeutic effects throughout the day without requiring multiple doses 5, 6
- Following oral administration of 70mg radiolabeled Vyvanse, approximately 96% of radioactivity is recovered in urine over 120 hours, with 42% related to amphetamine, 25% to hippuric acid, and only 2% to intact lisdexamfetamine 1
Important Clinical Considerations
- Food does not affect the total exposure (AUC) or peak concentration (Cmax) of d-amphetamine, but prolongs Tmax by approximately 1 hour (from 3.8 hours fasted to 4.7 hours after high-fat meal) 1
- The chewable tablet formulation produces approximately 15% lower exposure to lisdexamfetamine compared to capsules, but d-amphetamine exposure remains similar between formulations 1
- Lisdexamfetamine is not metabolized by cytochrome P450 enzymes, reducing potential for drug-drug interactions affecting its metabolism 1