What is the half-life of Vyvanse (lisdexamfetamine)?

Half-Life of Vyvanse (Lisdexamfetamine)

The plasma elimination half-life of lisdexamfetamine is typically less than one hour, while its active metabolite dextroamphetamine has a half-life of approximately 10 to 11.3 hours in healthy adults. 1

Pharmacokinetic Properties of Lisdexamfetamine

• Lisdexamfetamine is a prodrug that remains pharmacologically inactive until enzymatically converted to the active ingredient d-amphetamine and the amino acid lysine 2
• The conversion of lisdexamfetamine to d-amphetamine occurs primarily in the blood due to the hydrolytic activity of red blood cells 1
• Plasma concentrations of unconverted lisdexamfetamine are low and transient, generally becoming non-quantifiable by 8 hours after administration 1
• The elimination half-life of the parent compound lisdexamfetamine is short, averaging less than one hour in individuals 6 years and older 1

Dextroamphetamine Half-Life and Elimination

• After lisdexamfetamine is converted, the active metabolite dextroamphetamine has a half-life of approximately 10-11.3 hours in healthy adults 1
• In pediatric patients aged 6-12 years, the half-life of dextroamphetamine is slightly shorter at approximately 8.6-9.5 hours 1
• Systemic exposure to d-amphetamine is approximately 20-fold higher than systemic exposure to intact lisdexamfetamine dimesylate 3

Metabolism and Excretion

• Following oral administration of lisdexamfetamine, approximately 96% of the dose is recovered in urine and only 0.3% in feces over a 120-hour period 1, 3
• Of the radioactivity recovered in urine, approximately 42% is related to amphetamine, 25% to hippuric acid, and only 2% to intact lisdexamfetamine 1
• Lisdexamfetamine is not metabolized by cytochrome P450 enzymes, which reduces the potential for drug-drug interactions involving these pathways 1

Clinical Implications of Half-Life

• The relatively long half-life of the active d-amphetamine metabolite (10-11.3 hours) allows for once-daily dosing of lisdexamfetamine 2
• Drugs with shorter half-lives generally require more frequent dosing to maintain uniform blood levels and reduce adverse effect risk 4
• The duration of action of lisdexamfetamine extends for approximately 14 hours post-dosing in adults, providing consistent symptom control throughout the day 5

Special Considerations

• The half-life of drugs can be influenced by factors such as age, concurrent medications, and presence of liver or renal disease 4
• For drugs with long half-lives (>2 days), occasional missed doses may have minimal impact on therapeutic effect, but this is less applicable to lisdexamfetamine given its shorter half-life 6
• The relatively short half-life of lisdexamfetamine compared to some other psychotropic medications means that it will wash out of the system more quickly when discontinued 6

Understanding the half-life of Vyvanse is important for predicting its duration of action, timing of doses, and how quickly it will be eliminated from the body after discontinuation.