Comparative pharmacology and abuse potential of oral dexamphetamine and lisdexamfetamine-A literature review

Hum Psychopharmacol. 2024 Nov;39(6):e2910. doi: 10.1002/hup.2910. Epub 2024 Jul 18.

Abstract

Objective: To compare the pharmacology and abuse potential of oral dexamphetamine and lisdexamfetamine (LDX).

Methods: A search of Medline and Embase was conducted to identify relevant articles for this literature review.

Results: Dexamphetamine and LDX, a prodrug of dexamphetamine, are indicated for the treatment of attention-deficit/hyperactivity disorder. It has been suggested that LDX may have a reduced potential for oral abuse compared to immediate-release dexamphetamine. As a prodrug, LDX has the same pharmacodynamic properties as dexamphetamine. A study in healthy adults showed that the pharmacokinetic profile of dexamphetamine following oral administration of LDX is essentially identical to that of an equimolar dose of dexamphetamine administered 1 h later. In addition, dexamphetamine produced subjective drug liking effects comparable to those produced by LDX. LDX showed linear dose proportional pharmacokinetics up to a dose of 250 mg, indicating a lack of overdose protection at supratherapeutic doses. Furthermore, the exposure to dexamphetamine released from LDX may be prolonged by the consumption of alkalizing agents.

Conclusions: The available evidence from pharmacodynamic, pharmacokinetic and abuse liability studies suggests a comparable potential for oral abuse of dexamphetamine and LDX.

Keywords: abuse; dexamphetamine; lisdexamfetamine; pharmacokinetics; pharmacology.

Publication types

  • Review
  • Comparative Study

MeSH terms

  • Administration, Oral
  • Animals
  • Attention Deficit Disorder with Hyperactivity / drug therapy
  • Central Nervous System Stimulants* / administration & dosage
  • Central Nervous System Stimulants* / adverse effects
  • Central Nervous System Stimulants* / pharmacokinetics
  • Dextroamphetamine* / administration & dosage
  • Dextroamphetamine* / adverse effects
  • Dextroamphetamine* / pharmacokinetics
  • Dose-Response Relationship, Drug
  • Humans
  • Lisdexamfetamine Dimesylate* / administration & dosage
  • Lisdexamfetamine Dimesylate* / adverse effects
  • Lisdexamfetamine Dimesylate* / pharmacokinetics
  • Prodrugs / administration & dosage
  • Prodrugs / adverse effects
  • Prodrugs / pharmacokinetics
  • Substance-Related Disorders

Substances

  • Central Nervous System Stimulants
  • Dextroamphetamine
  • Lisdexamfetamine Dimesylate
  • Prodrugs