Absorption and Presystemic Metabolism of Selegiline Hydrochloride at Different Regions in the Gastrointestinal Tract in Healthy Males

  title={Absorption and Presystemic Metabolism of Selegiline Hydrochloride at Different Regions in the Gastrointestinal Tract in Healthy Males},
  author={Jeffrey S. Barrett and Peter L Szego and Shashank Rohatagi and Richard J. Morales and Kimberly E. DeWitt and Gregory Rajewski and Joyce Ireland},
  journal={Pharmaceutical Research},
AbstractPurpose. The absorption and disposition of selegiline (SEL) and its metabolites N-desmethylselegiline (DMS), L-methamphetamine (MET), and L-amphetamine (AMP) were assessed in 8 healthy male volunteers at proximal and distal regions of the intestine relative to oral administration (in the stomach) to determine if intestinal site dependence contributed to the erratic oral absorption of selegiline hydrochloride which is manifest as low and variable bioavailability. Methods. An open-label… 
Pressor Response to Tyramine after Single 24‐Hour Application of a Selegiline Transdermal System in Healthy Males
Systemic selegiline levels may not predict the propensity for a hypertensive crisis associated with presumed nonselective doses and that the avoidance of peripheral monoamine oxidase type A inhibition in the gut via the seLegiline transdermal system may provide a safe vehicle for administering selegILine at plasma levels beyond that which can be safely obtained after oral administration.
Absorption sites of orally administered drugs in the small intestine
The author summarizes the reported absorption sites of orally administered drugs, as well as, influencing factors and experimental techniques, which can help to develop ideal drug delivery systems and more effective pharmacotherapies.
R-Deprenyl: Pharmacological Spectrum of its Activity
R-Deprenyl elicits neuroprotective and neuronal rescue activities in concentrations too low to inhibit MAO-B, and was shown to prevent the detrimental effects of neurotoxins like MPTP and DSP-4.
Objectives: Curcumin, a known hMAO-A (human Monoamine oxidase-A) inhibitor from Curcuma longa has never been recognized for this property due to its poor permeability and extensive metabolism. Thus,
Monoamine Oxidase Inhibitory Activity of Ferulic Acid Amides: Curcumin‐Based Design and Synthesis
Compounds 6f, 6j, and 6k were subjected to membrane permeability and metabolic stability studies by in vitro assay methods and were found to have a better pharmacokinetic profile than curcumin, ferulic acid, and selegiline.
R-2HMP: an Orally Active Agent Combining Independent Antiapoptotic and MAO-B-Inhibitory Activities
The present review will describe the development and known activity of the lead compound R-N-(2heptyl)-N-methylpropargylamine hydrochloride (R-2HMP) and at least one of the metabolites of this lead compound appears to be responsible for the antiapoptotic effect while being essentially devoid of MAO-B-inhibitory activity.
Impact of Roux-en-Y Gastric Bypass Surgery on Pharmacokinetics of Administered Drugs: Implications and Perspectives
  • N. Srinivas
  • Medicine, Biology
    American journal of therapeutics
  • 2016
Based on the review, there is a significant risk of therapy failure for certain drugs because of subtherapeutic plasma levels and the need to readjust doses immediately after RYGB may be considered based on the therapeutic drug monitoring (TDM) findings.
Monoamine Oxidase Inhibitory Activity of Novel Pyrazoline Analogues: Curcumin Based Design and Synthesis
A series of new 2-methoxy-4-(5-phenyl-4,5-dihydro-1H-pyrazol-3-yl)phenolderivatives, 4–13, were synthesized and tested for their human MAO inhibitory activity, finding 4, a selective inhibitor of hMAO-B and 12, a nonselective inhibitor.
Nanoparticles for the Oral Administration of Cancer Therapies
It will be necessary more studies clarifying the correlation between nanoparticles properties and their interaction with the gut mucosa, their transport through and their final outcome to overcome the major obstacles to cancer drugs gastrointestinal absorption.
Basic cell physiological activities (cell adhesion, chemotaxis and proliferation) induced by selegiline and its derivatives in Mono Mac 6 human monocytes
The adhesion inducer activity, chemorepellent and advantageous cytotoxic effects of selegiline and some derivatives indicate that these drug molecules might have inhibitory effects in metastasis formation in primary tumors.


Absorption and Presystemic Metabolism of Nefazodone Administered at Different Regions in the Gastrointestinal Tract of Humans
NEF is absorbed throughout the length of the gastrointestinal tract which supports the development of an extended-release formulation of NEF.
Pharmacokinetics and relative bioavailability of selegiline in healthy volunteers
The pharmacokinetics and relative bioavailability of selegiline were investigated in healthy volunteers following oral administration of 10 mg tablet or solution and aparent oral plasma clearance was comparatively high and indicates rapid elimination of seLegiline from the body.
Site-Differential Gastrointestinal Absorption of Benazepril Hydrochloride in Healthy Volunteers
It can be concluded that COLON delivered a smaller amount of drug at a slower absorption rate to the body than either SI or ORAL, indicating the mechanism of absorption of BZPH in the colon may be different than that after SI and ORAL.
Pharmacokinetic aspects of l‐deprenyl (selegiline) and its metabolites *
Studies with positron emission tomography have shown retention of selegiline in brain areas with high MAO‐B activity, including striatal structures, hippocampus, thalamus, and substantia nigra, as well as in humans.
Sumatriptan Absorption from Different Regions of the Human Gastrointestinal Tract
Results suggest that presystemic metabolism of sumatriptan varies throughout the gastrointestinal tract and/or regional differences exist in the absorption of metabolite formed within theintestinal tract.
Hepatic and extrahepatic metabolism of deprenyl, a selective monoamine oxidase (MAO) B inhibitor, of amphetamines in rats: sex and strain differences.
Sex differences in the hepatic metabolism of deprenyl to amphetamines were seen in all three strains of rats, Sprague-Dawley, Wistar and Donryu, however, no sex differences observed in the extrahepatic metabolism.
Extrahepatic Metabolism of Drugs in Humans
The metabolic profile and sites of enzymatic reactions for each drug should be determined and extrahepatic metabolism has been demonstrated for numerous drugs.