Comparative Pharmacology and Abuse Potential of Oral Dexamphetamine and Lisdexamfetamine-A Literature Review

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.