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Related Concept Videos

Drug Clearance: Overview01:06

Drug Clearance: Overview

430
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...
430
Hepatic Drug Clearance: Restrictive and Nonrestrictive Clearance01:09

Hepatic Drug Clearance: Restrictive and Nonrestrictive Clearance

520
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...
520
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,...
4.0K
Renal Drug Clearance: Overview01:06

Renal Drug Clearance: Overview

780
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...
780
Factors Affecting Renal Clearance: Drug Distribution and Drug Interactions01:09

Factors Affecting Renal Clearance: Drug Distribution and Drug Interactions

540
Renal clearance plays a pivotal role in drug elimination from the body and can be influenced by drug distribution and interactions. Understanding these factors is crucial in pharmacology as they impact the effectiveness and duration of drug therapy.
One important factor is the relationship between renal clearance and the apparent volume of distribution. Renal clearance tends to be inversely proportional to the apparent volume of distribution. Drugs with an extensive distribution volume or those...
540
Hepatic Drug Clearance: Effect of Protein Binding01:09

Hepatic Drug Clearance: Effect of Protein Binding

559
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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In vivo Evaluation of Mucociliary Clearance in Mice
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Clearance in Drug Design.

Dennis A Smith1, Kevin Beaumont2, Tristan S Maurer2

  • 14 The Maltings , Walmer , Kent CT14 7AR , U.K.

Journal of Medicinal Chemistry
|October 4, 2018
PubMed
Summary
This summary is machine-generated.

Drug clearance, a key pharmacokinetic parameter, involves metabolism, renal, and hepatobiliary excretion. Optimizing drug candidates requires understanding these mechanisms and improving prediction tools, especially for transporter-mediated clearance.

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Area of Science:

  • Pharmacokinetics
  • Drug Discovery
  • Drug Metabolism and Transport

Background:

  • Clearance rate is a critical pharmacokinetic parameter influencing drug dosage and frequency.
  • Understanding clearance mechanisms is vital for effective drug candidate design.
  • Clearance is broadly categorized into metabolic transformation, renal excretion, and hepatobiliary excretion.

Purpose of the Study:

  • To review the major clearance mechanisms in drug development.
  • To highlight the importance of physiochemical properties in predicting clearance pathways.
  • To assess the current state and limitations of tools for predicting human clearance.

Main Methods:

  • Literature review of pharmacokinetic principles and drug clearance mechanisms.
  • Analysis of structure-clearance relationships based on molecular properties.
  • Evaluation of in vitro and in vivo methods for clearance prediction.

Main Results:

  • Physiochemical properties correlate with clearance mechanisms (lipophilic molecules favor metabolism, hydrophilic molecules favor excretion).
  • Existing methods for predicting metabolic and passive renal clearance are relatively robust.
  • Significant limitations exist in current tools for predicting transporter-mediated clearance.

Conclusions:

  • Optimizing drug clearance necessitates recognizing major mechanisms and employing relevant predictive tools.
  • There is a critical need for enhanced methods to accurately predict transporter-mediated clearance.
  • Improved prediction of transporter-mediated clearance is essential for successful drug development.