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Related Concept Videos

Clearance Models: Compartment Models01:25

Clearance Models: Compartment Models

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 of...
Clearance Models: Noncompartmental Models01:17

Clearance Models: Noncompartmental Models

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...
Compartment Models: Single-Compartment Model01:14

Compartment Models: Single-Compartment Model

The single-compartment model serves as a simplified representation of the human body. This model assumes that the body functions as a single, well-mixed open compartment. When a drug is administered intravenously, it enters the body and quickly distributes uniformly. The drug then undergoes biotransformation and elimination, ultimately leaving the body. The volume of this compartment is referred to as the apparent volume of distribution into which the drug can uniformly distribute. In this...
Clearance Models: Physiological Models01:09

Clearance Models: Physiological Models

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 proficiency in drug...
Compartment Models: Two-Compartment Model01:20

Compartment Models: Two-Compartment Model

The two-compartment model divides the body into central and peripheral compartments to account for varying blood perfusion rates among organs and tissues, affecting drug distribution. The central compartment includes blood and highly perfused tissues with rapid drug distribution, while the peripheral compartment contains tissues with slower drug distribution. After a single IV bolus dose, the drug concentration is high in plasma and low in tissues. The drug distribution between compartments...
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance01:23

Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance

The elimination half-life and drug clearance of drugs following nonlinear kinetics can vary with dosage. The Michaelis-Menten parameters and drug concentration influence these factors. As the dose increases, the elimination half-life tends to lengthen, resulting in a reduction in clearance and a disproportionately larger area under the curve. The total clearance can be derived from the Michaelis-Menten equation for drugs following a one-compartment model.
A study on guinea pigs examined the...

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Application of Dixon's Up-and-Down Design to Estimate the Minimum Alveolar Concentration of Sevoflurane in Rats with Refined Movement Classification
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A maturation model for midazolam clearance.

Brian J Anderson1, Peter Larsson

  • 1Department of Anaesthesiology, University of Auckland, Auckland, New Zealand. briana@adhb.govt.nz

Paediatric Anaesthesia
|August 14, 2010
PubMed
Summary
This summary is machine-generated.

This study developed a midazolam clearance maturation model from neonate to adulthood, using published data. The model accurately predicts drug clearance, aiding in pediatric dosing.

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Area of Science:

  • Pharmacokinetics
  • Pediatric Pharmacology
  • Drug Metabolism

Background:

  • Physiological-based pharmacokinetic models are used for midazolam clearance (CL) maturation.
  • Existing models lack comprehensive CL descriptors from neonate to adulthood.

Purpose of the Study:

  • To construct a midazolam CL maturation model based on published estimates.
  • To describe CL maturation from infancy through adulthood.

Main Methods:

  • Utilized published CL estimates from intravenous administration time-concentration profiles.
  • Employed nonlinear mixed-effects models for curve fitting.
  • Developed a size and age-based maturation model using the Hill equation.

Main Results:

  • A mature CL of 523 ml·min⁻¹·70 kg⁻¹ was determined.
  • The maturation half-time was 73.6 weeks postmenstrual age (PMA).
  • The model showed close agreement with physiologically based pharmacokinetic (PBPK) models, with low prediction error (4.0%) and bias (-0.9%).

Conclusions:

  • Published pharmacokinetic data can inform drug disposition maturation models.
  • Anticipated midazolam infusion rates vary significantly with age in children.
  • Further research is needed to quantify pharmacodynamic differences and active metabolite effects.