Preclinical pharmacokinetics, pharmacology and toxicology of lisdexamfetamine: A novel d-amphetamine pro-drug

@article{Hutson2014PreclinicalPP,
  title={Preclinical pharmacokinetics, pharmacology and toxicology of lisdexamfetamine: A novel d-amphetamine pro-drug},
  author={Peter H. Hutson and Michael Pennick and Roger Secker},
  journal={Neuropharmacology},
  year={2014},
  volume={87},
  pages={41-50}
}
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.
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.
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: A pharmacokinetic review.
Running title : Pharmacokinetics of lisdexamfetamine
TLDR
This article revises the pharmacokinetic studies on LDX, the newest amphetamine pro-drug used to treat Attention Deficit and Hyperactivity Disorder (ADHD) and Binge Eating Disorder (BED) symptoms, gathering data from all clinical pharmacokinetics studies available in the literature.
Single Dose Comparative Bioavailability Study of Lisdexamfetamine Dimesylate as Oral Solution Versus Reference Hard Capsules in Healthy Volunteers
TLDR
A fully validated HPLC-MS/MS analytical method for simultaneous determination of lisdexam Fetamine and dexamfetamine in human plasma and the first published comparative bioavailability study of lisexamfetamines including a GMP finished product formulated as oral solution is presented.
The Clinical Pharmacokinetics of Amphetamines Utilized in the Treatment of Attention-Deficit/Hyperactivity Disorder.
TLDR
The array of AMP formulations addressed in this review offer flexibility in dosing, drug onset, and offset to assist in individualized pharmacotherapy of ADHD, and some metabolic pathways exhibit stereoselective biotransformations favoring the l-isomer substrate.
Review of Lisdexamfetamine Dimesylate in Adults With Attention-Deficit/Hyperactivity Disorder
TLDR
Lisdexamfetamine dimesylate has demonstrated efficacy at 14 hours post dose in adults and may be used as a long-acting stimulant for managing ADHD symptoms, which may extend late into the day.
Pharmacokinetic-Pharmacodynamic (PKPD) Analysis with Drug Discrimination.
  • S. Negus, M. Banks
  • Biology, Medicine
    Current topics in behavioral neurosciences
  • 2018
Discriminative stimulus and other drug effects are determined by the concentration of drug at its target receptor and by the pharmacodynamic consequences of drug-receptor interaction. For in vivo
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References

SHOWING 1-10 OF 46 REFERENCES
Absorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine
  • M. Pennick
  • Biology, Medicine
    Neuropsychiatric disease and treatment
  • 2010
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.
Amphetamine, past and present – a pharmacological and clinical perspective
TLDR
The review charts advances in pharmaceutical development from the introduction of once-daily formulations of amphetamine through to lisdexamfetamine, which is the first d-amphetamine prodrug approved for the management of ADHD in children, adolescents and adults.
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.
Studies on sympathomimetic amines. II. The biotransformation and physiological disposition of d-amphetamine, d-p-hydroxyamphetamine and d-methamphetamine.
  • J. Axelrod
  • Biology, Chemistry
    The Journal of pharmacology and experimental therapeutics
  • 1954
TLDR
d-Amphetamine disappears slowly in the dog compared to its hydroxylated derivative, suggesting that in this species the major part of the pharmacological effect of the drug is due to the parent compound.
Lisdexamfetamine: a prodrug for the treatment of attention-deficit/hyperactivity disorder.
TLDR
Clinical trials in children age 6-12 years and adults with ADHD have shown lisdexamfetamine to be safe and effective, with significant improvement of ADHD-related rating scores, however, the efficacy and safety in children with ADHD and comorbid psychiatric disorders have not been assessed.
Toxicity profile of lisdexamfetamine dimesylate in three independent rat toxicology studies.
TLDR
The findings of the repeat-dose studies indicate that the toxicity profile in rats administered LDX orally is comparable to that for d- methamphetamine; however, the apparent lethal dose of LDX in rats is more than five times higher than the LD(50) of orally administered d-amphetamine, supporting a putative protective effect of conjugating amphetamine with lysine.
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