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Related Concept Videos

Clearance Models: Physiological Models01:09

Clearance Models: Physiological Models

62
Drug clearance is a critical pharmacokinetic process involving the irreversible removal of drugs from the body through various organs over a specified time period. Physiological models are indispensable in determining organ-specific clearance, defined by the proportion of the drug eliminated per unit of time from the organ's blood volume.
The organ's clearance rate depends on the blood flow to the organ and the extraction ratio (E). The extraction ratio describes the organ's...
62
One-Compartment Open Model: Urinary Excretion Data and Determination of k01:11

One-Compartment Open Model: Urinary Excretion Data and Determination of k

171
The one-compartment open model leverages urinary excretion data to estimate renal clearance, which gauges the kidney's capacity to expel a drug. This method offers several benefits, including directly measuring drug elimination and assessing the kidney's contribution to overall drug clearance. However, this approach has limitations. It assumes sole renal excretion of the drug, which is not true for all drugs. Accurate urinary excretion and plasma drug concentration measurement can also...
171
One-Compartment Open Model for IV Bolus Administration: Estimation of Clearance00:56

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

72
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...
72
Clearance Models: Compartment Models01:25

Clearance Models: Compartment Models

74
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...
74
Renal Drug Clearance: Overview01:06

Renal Drug Clearance: Overview

181
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...
181
Renal Drug Clearance: Comparison Between Renal Excretion Methods01:08

Renal Drug Clearance: Comparison Between Renal Excretion Methods

122
Renal clearance is a critical parameter encompassing kidney filtration, secretion, and reabsorption processes. It is calculated using a specific equation to determine the rate at which the kidneys clear a drug.
Renal clearance is often associated with the renal glomerular filtration rate (GFR), which represents the rate at which plasma is filtered through the glomeruli in the kidney. When drug reabsorption is minimal and there is no active secretion, renal clearance is closely related to the...
122

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Physiology Lab Demonstration: Glomerular Filtration Rate in a Rat
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A physiological model for iohexol plasma clearance supporting diagnostics of kidney function.

Bertil Kågedal1, Carl-Fredrik Mandenius2

  • 1Department of Clinical Chemistry and Clinical Pharmacology and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.

Clinica Chimica Acta; International Journal of Clinical Chemistry
|June 25, 2024
PubMed
Summary

This study developed a new physiologically based mass balance model to accurately estimate kidney function. The model improves plasma clearance calculations for iohexol, offering a more precise alternative to existing methods.

Keywords:
Distribution to extracellular spacesGlomerular filtration rateIohexolIohexol plasma clearanceMass balance modelling

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Area of Science:

  • Biochemical Engineering
  • Pharmacokinetics
  • Renal Physiology

Background:

  • Current methods for estimating Glomerular Filtration Rate (GFR) from plasma clearance have limitations.
  • Accurate GFR estimation is crucial for clinical decision-making and drug dosing.

Purpose of the Study:

  • To develop a physiologically based method for calculating plasma clearance of iohexol.
  • To address shortcomings in existing GFR estimation techniques.

Main Methods:

  • A mechanistic mass balance model was developed based on biochemical engineering principles.
  • In- and outgoing molecular flows of iohexol between plasma and tissues were balanced over time.
  • Plasma samples were collected post-intravenous iohexol injection until complete elimination.

Main Results:

  • The mass balance model accurately predicted iohexol distribution and elimination kinetics.
  • The model's iohexol clearance calculations were validated against established methods.
  • Accurate clearance was estimated in ten healthy subjects using the mass balance model.

Conclusions:

  • The physiologically based mass balance model provides a more accurate in vivo clearance estimation compared to traditional methods.
  • This model, validated with iohexol, is potentially applicable to other renal clearance markers.
  • The mechanistic approach enhances the reliability of clearance measurements.