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Related Concept Videos

Clearance Models: Compartment Models01:25

Clearance Models: Compartment Models

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Clearance measures drug elimination from the central compartment, including plasma and highly perfused organs like kidneys and liver. Its calculation varies depending on pharmacokinetic models and administration routes. The one-compartment model, for instance, portrays the pharmacokinetics of polar drugs such as aminoglycoside antibiotics administered intravenously and readily excreted in urine. In this case, clearance is influenced by the terminal rate constant (λz) and the total volume...
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Drug Elimination: The Concept of Clearance01:06

Drug Elimination: The Concept of Clearance

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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.
Drug clearance is not limited to renal excretion but encompasses all organs involved in drug elimination,...
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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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Hepatic Drug Clearance: Effect of Protein Binding01:09

Hepatic Drug Clearance: Effect of Protein Binding

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Hepatic clearance is influenced by protein binding based on the drug's extraction ratio. Drugs with high extraction ratios are considered flow-limited and remain unaffected by protein binding during hepatic clearance. On the other hand, drugs with low extraction ratios may be impacted by plasma protein binding, although the extent of this influence depends on the fraction of the drug bound.
For low-extraction-ratio drugs that are less than 80% protein-bound, minor changes in protein binding...
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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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One-Compartment Open Model for IV Bolus Administration: Estimation of Clearance00:56

One-Compartment Open Model for IV Bolus Administration: Estimation of Clearance

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Clearance is a key pharmacokinetic parameter that quantifies the volume of body fluid from which a drug is entirely removed within a specific time frame. It is crucial in assessing how a drug is eliminated from the body and has critical clinical applications.
In the one-compartment open model for intravenous (IV) bolus administration, clearance is estimated by dividing the elimination rate by the plasma drug concentration. This equation leverages the elimination rate constant and the apparent...
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Optimized Griess Reaction for UV-Vis and Naked-eye Determination of Anti-malarial Primaquine
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CLEARance wars: PolyQ strikes back.

X William Yang1, Ai Yamamoto2

  • 1Department of Psychiatry and Biobehavioral Sciences and Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.

Nature Neuroscience
|August 27, 2014
PubMed
Summary
This summary is machine-generated.

Polyglutamine expansion in androgen receptors causes X-linked spinal and bulbar muscular atrophy by impairing transcriptional coactivator function. This dysfunction affects protein clearance networks, impacting cellular health.

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • X-linked spinal and bulbar muscular atrophy (SBMA) is a neurodegenerative disease.
  • SBMA is caused by polyglutamine expansion in the androgen receptor (AR).
  • The AR functions as a transcriptional coactivator.

Purpose of the Study:

  • To investigate how polyglutamine expansion in AR affects its function.
  • To understand the downstream consequences of AR dysfunction on protein clearance.

Main Methods:

  • The study likely involved molecular and cellular assays to assess AR function.
  • Analysis of protein networks involved in protein clearance.

Main Results:

  • Polyglutamine expansion impairs the AR's ability to act as a transcriptional coactivator.
  • This impairment disrupts the regulation of proteins involved in protein clearance.

Conclusions:

  • AR polyglutamine expansion is a key mechanism in SBMA pathogenesis.
  • Dysregulation of protein clearance pathways contributes to SBMA.
  • Targeting protein clearance may offer therapeutic strategies for SBMA.