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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.
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 assumptions,...
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...
Toxicokinetics: Overview01:21

Toxicokinetics: Overview

Studies that assess how a drug is absorbed, distributed, metabolized, and excreted (ADME) at toxic doses are termed toxicokinetics. Understanding toxicokinetics helps predict adverse drug reactions (ADRs) and manage toxicity in humans.Toxicokinetics differs from pharmacokinetics mainly in the dose levels studied, with toxicokinetics focusing on higher toxic doses. The kinetics at these levels can be non-linear due to altered physiological processes. Toxicodynamics examines the relationship...
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...
Pharmacodynamic Models: Linear Concentration–Effect Model01:15

Pharmacodynamic Models: Linear Concentration–Effect Model

The linear concentration–effect model, underpinned by the principle that pharmacological effect (E) is directly proportional to plasma drug concentration (C), emerges as a pivotal simplification of the Emax model for conditions where C is significantly less than EC50. This model portrays a linear trajectory of the concentration–effect relationship when drug levels are markedly below the EC50 threshold.Despite its inherent assumption of continuous effect augmentation with increasing drug...

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An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
08:59

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment

Published on: December 3, 2020

A physiologically based toxicokinetic modelling approach to predict relevant concentrations for in vitro testing.

Hans Mielke1, Lennart T Anger, Markus Schug

  • 1Federal Institute for Risk Assessment, Thielallee 88-92, 14195, Berlin, Germany. hans.mielke@bfr.bund.de

Archives of Toxicology
|November 4, 2010
PubMed
Summary

This study used biologically-based pharmacokinetic modeling (BPTK) to simulate chemical concentrations in liver cells. This approach aids in planning in vitro studies as a safer alternative to animal testing for carcinogenicity.

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Area of Science:

  • Pharmacokinetics and Toxicological Sciences
  • In Vitro Toxicology
  • Computational Biology

Background:

  • In vitro primary hepatic cell cultures are explored as alternatives to in vivo cancerogenic bioassays.
  • Previous studies involved 2-year bioassays and 14-day short-term studies for 29 substances.
  • Accurate dose simulation is crucial for effective in vitro study design.

Purpose of the Study:

  • To simulate the concentration-time profile of substances administered orally.
  • To evaluate the utility of Biologically-Based Pharmacokinetic Modeling (BPTK) for planning in vitro studies.
  • To model compound concentrations in portal vein, hepatic vein, and systemic circulation.

Main Methods:

  • Developed a seven-tissue compartment model simulating oral uptake from the gastrointestinal tract.
  • Incorporated absorption percentage and utilized a biologically-based algorithm for blood:tissue partitioning.
  • Focused on modeling concentrations without initial elimination to prioritize hepatic and systemic circulation.

Main Results:

  • Substance kinetic profiles varied based on blood:tissue partitioning.
  • Maximal concentrations in portal vein, hepatic vein, and blood were primarily dependent on dose and fraction absorbed.
  • BPTK modeling successfully simulated compound concentrations relevant for in vitro study dose planning.

Conclusions:

  • Biologically-Based Pharmacokinetic Modeling (BPTK) is a valuable tool for simulating in vitro study conditions.
  • This modeling approach offers a more robust alternative to relying solely on in vitro cytotoxicity data.
  • BPTK aids in optimizing experimental design for in vitro hepatic cell culture studies.