Lisdexamfetamine and immediate release d-amfetamine – Differences in pharmacokinetic/pharmacodynamic relationships revealed by striatal microdialysis in freely-moving rats with simultaneous determination of plasma drug concentrations and locomotor activity

@article{Rowley2012LisdexamfetamineAI,
  title={Lisdexamfetamine and immediate release d-amfetamine – Differences in pharmacokinetic/pharmacodynamic relationships revealed by striatal microdialysis in freely-moving rats with simultaneous determination of plasma drug concentrations and locomotor activity},
  author={Helen L. Rowley and Rajiv S. Kulkarni and J Gosden and Richard J Brammer and David Hackett and David J. Heal},
  journal={Neuropharmacology},
  year={2012},
  volume={63},
  pages={1064-1074}
}
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52 Citations
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52 Citations

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Pharmacokinetics and Pharmacodynamics of Lisdexamfetamine Compared with D-Amphetamine in Healthy Subjects
TLDR
The pharmacokinetics and pharmacodynamics of lisdexamfetamine are similar to D-amphetamine administered 1h later, and are likely associated with a similar risk of oral abuse as D- methamphetamine.
Differences in the neurochemical and behavioural profiles of lisdexamfetamine methylphenidate and modafinil revealed by simultaneous dual-probe microdialysis and locomotor activity measurements in freely-moving rats
TLDR
The neurochemical and behavioural profiles of lisdexamfetamine, methylphenidate and modafinil were compared by dual-probe microdialysis in the prefrontal cortex (PFC) and striatum of conscious rats with simultaneous locomotor activity measurement, showing larger and more sustained effects on catecholaminergic neurotransmission.
Preclinical pharmacokinetics, pharmacology and toxicology of lisdexamfetamine: A novel d-amphetamine pro-drug
A preclinical evaluation of the discriminative and reinforcing properties of lisdexamfetamine in comparison to d -amfetamine, methylphenidate and modafinil
Effects of lisdexamfetamine on plasma steroid concentrations compared with d-amphetamine in healthy subjects: A randomized, double-blind, placebo-controlled study
Effects of Lisdexamfetamine, a Prodrug of D-Amphetamine, on Locomotion, Spatial Cognitive Processing and Neurochemical Profiles in Rats: A Comparison With Immediate-Release Amphetamine
TLDR
Results suggest that lisdexamfetamine was more effective than d-amphetamine in improving spatial cognitive performance, which was attributed to the steady and lasting dopamine release pattern within the mPFC.
Lisdexamfetamine and amphetamine pharmacokinetics in oral fluid, plasma, and urine after controlled oral administration of lisdexamfetamine
TLDR
There was a correlation between oral fluid and plasma d‐AMPH concentrations and between parent to metabolite concentration ratios over time in plasma as well as in oral fluid.
Lisdexamfetamine Dimesylate: Prodrug Delivery, Amphetamine Exposure and Duration of Efficacy
TLDR
Drug-liking scores for LDX are lower than for an equivalent dose of IR d-amphetamine, which may result from the reduced euphorigenic potential associated with its pharmacokinetic profile.
Role of d-amphetamine and d-methamphetamine as active metabolites of benzphetamine: Evidence from drug discrimination and pharmacokinetic studies in male rhesus monkeys
The effects in rats of lisdexamfetamine in combination with olanzapine on mesocorticolimbic dopamine efflux, striatal dopamine D2 receptor occupancy and stimulus generalization to a d-amphetamine cue
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References

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Lisdexamfetamine Dimesylate and Mixed Amphetamine Salts Extended-Release in Children with ADHD: A Double-Blind, Placebo-Controlled, Crossover Analog Classroom Study
Metabolism, Distribution and Elimination of Lisdexamfetamine Dimesylate
TLDR
Lisdexamfetamine dimesylate was quickly absorbed, extensively metabolized to d-amphetamine and its derivatives, and rapidly eliminated following a single 70 mg oral dose in normal, healthy adult subjects.
Efficacy and tolerability of lisdexamfetamine dimesylate (NRP-104) in children with attention-deficit/hyperactivity disorder: a phase III, multicenter, randomized, double-blind, forced-dose, parallel-group study.
Multiple daily-dose pharmacokinetics of lisdexamfetamine dimesylate in healthy adult volunteers
TLDR
This study describes the steady-state pharmacokinetics of LDX, a new pro-drug stimulant developed with the goal of providing an extended effect that is consistent throughout the day, with a reduced potential for abuse, overdose toxicity, and drug tampering.
The neuropharmacology of ADHD drugs in vivo: Insights on efficacy and safety
Absorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine
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TLDR
The carrier-mediated absorption of intact LDX, likely by the high-capacity PEPT1 transporter, and subsequent metabolism to d-amphetamine in a high- capacity system in blood (ie, red blood cells) may contribute to the consistent, reproducible pharmacokinetic profile of LDX.
Human pharmacology of intravenous lisdexamfetamine dimesylate: abuse liability in adult stimulant abusers
TLDR
LDX administered intravenously did not produce significant subjective abuse-related liking scores at assessed doses, and was well tolerated in this population of adult substance abusers.
Methylphenidate and its Isomers
TLDR
It is concluded that d-threo-methylphenidate, which is the more potent and abundant of the two isomers, is the major contributor of both efficacy and adverse effects, irrespective of the formulation or route of administration of the racemate.
Simultaneous measurement of dopamine release and rotational behaviour in 6-hydroxydopamine denervated rats using intracerebral dialysis
Abuse liability and safety of oral lisdexamfetamine dimesylate in individuals with a history of stimulant abuse
TLDR
At an equivalent amount of amphetamine base taken orally, LDX 100 mg had attenuated responses on measures of abuse liability compared with immediate-release d-amphetamine 40 mg, and diethylpropion hydrochloride, a Schedule IV amphetamine-like stimulant, on abuse-related liking scores.
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