Absorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine.

Neuropsychiatric Disease and Treatment
Michael Pennick

Abstract

These studies investigated the absorption and metabolic conversion of lisdexamfetamine dimesylate (LDX), a prodrug stimulant that requires conversion to d-amphetamine for activity. Oral absorption of LDX was assessed in rat portal and jugular blood, and perfusion of LDX into isolated intestinal segments of anesthetized rats was used to assess regional absorption. Carrier-mediated transport of LDX was investigated in Caco-2 cells and Chinese hamster ovary (CHO) cells expressing human peptide transporter-1 (PEPT1). LDX metabolism was studied in rat and human tissue homogenates and human blood fractions. LDX was approximately10-fold higher in portal blood versus systemic blood. LDX and d-amphetamine were detected in blood following perfusion of the rat small intestine but not the colon. Transport of LDX in Caco-2 cells had permeability apparently similar to cephalexin and was reduced with concurrent PEPT1 inhibitor. Affinity for PEPT1 was also demonstrated in PEPT1-transfected CHO cells. LDX metabolism occurred primarily in whole blood (rat and human), only with red blood cells. Slow hydrolysis in liver and kidney homogenates was probably due to residual blood. The carrier-mediated absorption of intact LDX, likely by the high-capa...Continue Reading

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Citations

Oct 27, 2012·Advanced Drug Delivery Reviews·Balvinder S VigJarkko Rautio
May 3, 2014·CNS Drugs·David R CoghillRichard Civil
Jun 21, 2014·Expert Review of Neurotherapeutics·Carlos Roncero, F Javier Álvarez
Dec 18, 2012·Expert Opinion on Pharmacotherapy·Sharon B WigalAnkita Shukla
Mar 15, 2012·Expert Opinion on Drug Metabolism & Toxicology·Sophie DuongSharon B Wigal
May 4, 2013·Expert Opinion on Investigational Drugs·Naren P Rao, Gary Remington
Dec 25, 2010·Seminars in Pediatric Neurology·Sharon B WigalRobin Steinberg-Epstein
Dec 2, 2015·European Eating Disorders Review : the Journal of the Eating Disorders Association·Susan L McElroyJames I Hudson
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May 21, 2014·Journal of the American Academy of Child and Adolescent Psychiatry·David R CoghillLiza A Squires
Apr 8, 2016·International Journal of Psychiatry in Clinical Practice·Gil Zalsman, Tal Shilton
Jul 21, 2015·Journal of Manipulative and Physiological Therapeutics·Carol Ann WeisJessica Roeder
Jan 22, 2013·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·David CoghillLiza Squires
Mar 23, 2011·Journal of the American Academy of Child and Adolescent Psychiatry·Robert L FindlingLiza Squires
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Dec 17, 2015·Journal of Correctional Health Care : the Official Journal of the National Commission on Correctional Health Care·Duncan A ScottGunter W Lorberg

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Methods Mentioned

BETA
PCR
scintillation spectrometry

Software Mentioned

GraphPad Prism

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