Half-Life of Lisdexamfetamine (Vyvanse)
Lisdexamfetamine (Vyvanse) has a short plasma elimination half-life of less than one hour for the parent compound, while its active metabolite d-amphetamine has a half-life of approximately 10-11.3 hours in healthy adults. 1
Pharmacokinetic Properties
Absorption and Conversion
- Lisdexamfetamine is a prodrug that remains pharmacologically inactive until enzymatically converted
- Conversion occurs primarily in red blood cells through hydrolysis 2
- After oral administration:
- Peak plasma concentration (Tmax) of lisdexamfetamine occurs at approximately 1 hour
- Peak plasma concentration of d-amphetamine occurs at approximately 3.5-4.4 hours 1
Metabolism and Elimination
- Lisdexamfetamine is converted to d-amphetamine and l-lysine primarily in blood due to red blood cell hydrolytic activity 1
- Key elimination characteristics:
- Lisdexamfetamine is not metabolized by cytochrome P450 enzymes
- Plasma concentrations of unconverted lisdexamfetamine become non-quantifiable by 8 hours after administration
- Following oral administration, approximately 96% of the dose is recovered in urine and only 0.3% in feces 1, 3
- Of the recovered urinary radioactivity, 42% is related to amphetamine, 25% to hippuric acid, and 2% to intact lisdexamfetamine 1
Clinical Implications of Half-Life
Duration of Action
- Despite the short half-life of the parent compound, the longer half-life of d-amphetamine (10-11.3 hours) provides clinical effects lasting throughout the day 1, 4
- Lisdexamfetamine has demonstrated efficacy at 14 hours post-dose in adults, making it suitable for managing ADHD symptoms that extend late into the day 2
Dosing Considerations
- The long half-life of the active metabolite allows for once-daily dosing 2
- Food may prolong the time to maximum concentration (Tmax) by approximately 1 hour but does not significantly affect overall exposure 1
Special Populations
- No significant differences in half-life have been reported based on gender
- Patients with renal insufficiency may require dosage adjustments as the drug is primarily eliminated through the kidneys 1
Practical Significance
The half-life of a medication has important clinical implications for dosing frequency, steady-state concentrations, and withdrawal potential 5. For lisdexamfetamine:
- The long half-life of the active d-amphetamine metabolite (10-11.3 hours) allows for once-daily dosing
- Steady-state levels are achieved without significant accumulation in healthy adults 1
- The prodrug nature of lisdexamfetamine may contribute to its lower abuse potential compared to immediate-release amphetamine formulations 4
Understanding the half-life characteristics of lisdexamfetamine helps clinicians optimize treatment regimens for patients with ADHD, ensuring appropriate coverage throughout the day while minimizing dosing frequency.