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Related Concept Videos

Hepatic Drug Clearance: Restrictive and Nonrestrictive Clearance01:09

Hepatic Drug Clearance: Restrictive and Nonrestrictive Clearance

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Hepatic clearance refers to the volume of blood cleared of a drug by the liver per unit of time. It plays a crucial role in drug metabolism and elimination. While hepatic clearance is commonly estimated by subtracting renal clearance from total body clearance, other pathways, such as pulmonary or biliary clearance, may also contribute. However, these pathways are generally less significant than hepatic and renal clearance.
Most drugs undergo restrictive clearance, which is proportional to the...
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Renal Clearance01:23

Renal Clearance

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The glomerular filtration rate (GFR) is a critical marker of kidney function, reflecting the efficiency of filtration by the glomeruli. Renal clearance of specific substances, such as inulin or creatinine, is commonly used to measure GFR.
Renal clearance refers to the volume of plasma cleared of a specific substance, such as creatinine, per unit of time. To measure clearance, urine samples are collected over a 24-hour period during each bladder voiding, followed by a single blood sample at the...
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Drug Clearance: Overview01:06

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Drug elimination refers to drug removal from the body, either through urine or bile, by the kidneys or liver, respectively. A pharmacokinetic parameter, drug clearance, measures the efficiency of drug removal from the bloodstream within a specific time frame. It is calculated as the rate at which a drug is eliminated from plasma divided by the drug's concentration in plasma.
Drug clearance is not limited to renal excretion but encompasses all organs involved in drug elimination, including...
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Clearance Models: Noncompartmental Models01:17

Clearance Models: Noncompartmental Models

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Clearance is a pharmacokinetic parameter traditionally defined by compartment models, signifying the rate at which a drug is expelled from the body. However, a noncompartmental model offers an alternative method for assessing clearance, primarily employing empirical data obtained after administering a single drug dose.
The noncompartmental approach capitalizes on extensive sampling data, correlating the volume of distribution to systemic exposure and the administered dosage. This method enables...
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Renal Drug Clearance: Overview01:06

Renal Drug Clearance: Overview

683
Renal clearance is a crucial parameter in pharmacokinetics that quantifies the rate at which the kidneys excrete a drug. It represents a constant fraction of the central volume of distribution containing the drug that the kidney eliminates per unit of time.
Renal clearance can be calculated using different methods. One approach is to divide the urinary drug excretion rate by the plasma drug concentration. This method directly measures renal clearance, indicating the kidneys' efficiency in...
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Drug Elimination: The Concept of Clearance01:06

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Drug elimination refers to removing drugs from the body, either through urine by the kidneys or through bile by the liver. Drug clearance is a pharmacokinetic parameter that measures the efficiency of drug removal from the bloodstream within a specific time frame. It is calculated as the rate at which a drug is eliminated from plasma divided by the plasma concentration of the drug.
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Plaque Assay for Murine Norovirus
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PPARα Between Aspirin and Plaque Clearance.

Sujyoti Chandra1, Avik Roy1,2, Dhruv R Patel1

  • 1Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.

Journal of Alzheimer'S Disease : JAD
|August 20, 2019
PubMed
Summary

Low-dose aspirin enhances cellular waste removal pathways, promoting the clearance of amyloid plaques associated with Alzheimer's disease (AD). This action involves stimulating lysosomal biogenesis and autophagy, offering a potential therapeutic avenue for AD.

Keywords:
Alzheimer’s diseasePPARαTFEBamyloid plaquesautophagylysosomal biogenesis

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Pharmacology

Background:

  • Impaired amyloid-β (Aβ) clearance is linked to Alzheimer's disease (AD) pathology.
  • The lysosome-autophagy network is crucial for degrading protein aggregates and maintaining cell health.
  • Targeting cellular degradative pathways for Aβ removal is a key area in AD research.

Purpose of the Study:

  • To review the emerging role of aspirin in stimulating cellular clearance mechanisms relevant to AD.
  • To elucidate the molecular pathways through which aspirin promotes amyloid plaque removal.

Main Methods:

  • Literature review of studies investigating aspirin's effects on lysosomal and autophagy pathways.
  • Analysis of molecular mechanisms, including transcription factor EB (TFEB) and peroxisome proliferator-activated receptor alpha (PPARα).

Main Results:

  • Low-dose aspirin was found to stimulate lysosomal biogenesis and autophagy.
  • Aspirin treatment led to the clearance of amyloid plaques in an animal model of AD.
  • The mechanism involves PPARα-mediated transcription of TFEB, a master regulator of lysosomal biogenesis.

Conclusions:

  • Aspirin, at low doses, demonstrates a novel therapeutic potential for Alzheimer's disease by enhancing Aβ clearance.
  • The findings highlight the importance of the PPARα-TFEB pathway in mediating aspirin's beneficial effects.
  • Further research into aspirin's mechanism could lead to new AD treatment strategies.