Related Experiment Video

Updated: Jun 11, 2025

Author Spotlight: Simulating Pediatric Cardiac Surgery Using a Neonatal Piglet Model
04:55

Author Spotlight: Simulating Pediatric Cardiac Surgery Using a Neonatal Piglet Model

Published on: May 26, 2023

729

Physiologically Based Pharmacokinetic Modelling in Critically Ill Children Receiving Anakinra While on Extracorporeal

Samuel Dubinsky1, Abdullah Hamadeh1, Carina Imburgia2

  • 1School of Pharmacy, Faculty of Science, University of Waterloo, Waterloo, ON, Canada.

Clinical Pharmacokinetics
|September 27, 2024
PubMed

Insights

A new physiologically based pharmacokinetic (PBPK) model for anakinra in critically ill children on extracorporeal life support (ECLS) was developed. This model accurately predicts drug concentrations and suggests similar anakinra exposure compared to healthy children.

Area of Science:

  • Pharmacokinetics
  • Pediatric Critical Care
  • Pharmacometrics

Background:

  • Critical illness and extracorporeal life support (ECLS) alter drug pharmacokinetics.
  • Accurate drug dosing is challenging in critically ill children on ECLS.

Purpose of the Study:

  • Develop a physiologically based pharmacokinetic (PBPK) model for anakinra in pediatric patients on ECLS.
  • Guide anakinra pharmacotherapy in this complex patient population.

Main Methods:

  • Extrapolated a PBPK model from healthy individuals to critically ill children.
  • Incorporated continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO) compartments into the PBPK model.
  • Validated the model using observed patient data and conducted in-silico dose simulations.

Main Results:

  • The developed ECLS-PBPK model accurately predicted anakinra plasma concentrations in an adolescent on ECLS.
  • In-silico simulations indicated comparable anakinra exposure in adolescents on ECLS versus healthy individuals.

Conclusions:

  • This is the first anakinra ECLS-PBPK model to predict drug concentrations in patients on simultaneous CRRT and ECMO.
  • The model and simulation data can inform anakinra dosing and aid future clinical trial design in critically ill children.
Abstract

More Related Videos

A Large Animal Model for Acute Kidney Injury by Temporary Bilateral Renal Artery Occlusion09:02

A Large Animal Model for Acute Kidney Injury by Temporary Bilateral Renal Artery Occlusion

Published on: February 2, 2021

4.4K
Standardized Colon Ascendens Stent Peritonitis in Rats - a Simple, Feasible Animal Model to Induce Septic Acute Kidney Injury07:03

Standardized Colon Ascendens Stent Peritonitis in Rats - a Simple, Feasible Animal Model to Induce Septic Acute Kidney Injury

Published on: February 15, 2022

1.4K

Related Concept Videos

Pharmacokinetic Models: Comparison and Selection Criterion01:26

Pharmacokinetic Models: Comparison and Selection Criterion

Physiological and compartmental models are valuable tools used in studying biological systems. These models rely on differential equations to maintain mass balance within the system, ensuring an accurate representation of the dynamic processes at play.
Physiological models take a detailed approach by considering specific molecular processes. They can predict drug distribution, metabolism, and elimination changes, providing a comprehensive understanding of how drugs interact with the body.
48
Pharmacokinetic Models: Overview01:20

Pharmacokinetic Models: Overview

Pharmacokinetic models utilize mathematical analysis to achieve a detailed quantitative understanding of a drug's life cycle within the body. They are instrumental in simulating a drug's pharmacokinetic parameters, predicting drug concentrations over time, optimizing dosage regimens, linking concentrations with pharmacologic activity, and estimating potential toxicity.
There are three primary types of models: empirical, compartment, and physiological. Empirical models, with minimal...
607
Model Approaches for Pharmacokinetic Data: Physiological Models01:15

Model Approaches for Pharmacokinetic Data: Physiological Models

Physiological models in pharmacokinetics are instrumental in understanding the distribution and elimination of drugs within the body. These models describe the drug concentration within target organs, influenced by factors such as drug uptake, tissue volume, and blood flow. Drug uptake is governed by the partition coefficient, which signifies the drug concentration ratio in tissue to that in the blood. The blood flow rate to a specific tissue is expressed as Qt, and the rate of change in tissue...
36
Model Approaches for Pharmacokinetic Data: Distributed Parameter Models01:06

Model Approaches for Pharmacokinetic Data: Distributed Parameter Models

Pharmacokinetic models are mathematical constructs that represent and predict the time course of drug concentrations in the body, providing meaningful pharmacokinetic parameters. These models are categorized into compartment, physiological, and distributed parameter models.
The distributed parameter models are specifically designed to account for variations and differences in some drug classes. This model is particularly useful for assessing regional concentrations of anticancer or...
63
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance01:07

Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance

Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
A recent model describes pravastatin's hepatobiliary excretion,...
34
Physiological Pharmacokinetic Models: Assumption with Protein Binding01:13

Physiological Pharmacokinetic Models: Assumption with Protein Binding

Physiological models with protein binding in pharmacokinetics offer a sophisticated approach to understanding drug disposition. These models consider drug-protein interactions, enabling them to effectively predict drug concentrations in different organs and tissues. This precision aids in accurate drug dosing, providing a significant advantage over conventional models. A key process within these models is equilibration, which ensures that drug concentrations achieve a steady state within the...
36