Related Experiment Video

Updated: Mar 12, 2026

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
11:06

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro

Published on: January 31, 2022

5.5K

Evolution of Experimental Models of the Liver to Predict Human Drug Hepatotoxicity and Efficacy

Lawrence A Vernetti1, Andreas Vogt1, Albert Gough1

  • 1Department of Computational and Systems Biology, University of Pittsburgh Drug Discovery Institute, Biomedical Science Tower 200 Lothrop Street, University of Pittsburgh, Pittsburgh, PA 15260, USA.

Clinics in Liver Disease
|November 16, 2016
PubMed

Insights

This review highlights how advanced in vitro models, like 3D microfluidic liver systems, are crucial for identifying hepatotoxins and advancing drug discovery using Quantitative Systems Pharmacology (QSP). These methods improve therapeutic development success rates.

Area of Science:

  • Toxicology and Pharmacology
  • Drug Discovery and Development

Background:

  • In vitro models have historically aided in identifying human hepatotoxins.
  • Traditional methods face limitations in predicting complex in vivo responses during drug development.

Purpose of the Study:

  • To review past applications of in vitro models for hepatotoxin identification.
  • To focus on multiscale experimental models in drug development, integrating Quantitative Systems Pharmacology (QSP).

Main Methods:

  • Review of literature on in vitro models for toxicology.
  • Application of multiscale experimental models, including zebrafish and 3D human cell-based microfluidic liver systems.
  • Implementation of Quantitative Systems Pharmacology (QSP) as a predictive platform.

Main Results:

  • In vitro models are evolving towards more complex, multiscale systems.
  • Integration of advanced models with QSP enhances the prediction of drug efficacy and toxicity.
  • The described platform aims to improve success rates in drug discovery.

Conclusions:

  • Multiscale experimental models, particularly 3D microfluidic liver systems, are vital for modern drug development.
  • Quantitative Systems Pharmacology (QSP) provides a robust framework for integrating these models.
  • This integrated approach promises to accelerate the development of safer and more effective therapeutics.
Keywords:
Drug discoveryDrug-induced liver injuryHuman liver modelsIn vitro hepatotoxicityLiver toxicologyMicrophysiology liverQuantitative system pharmacology

More Related Videos

Author Spotlight: Developing a Simple and Robust Hepatic Model for Pharmacological and Toxicological Applications07:23

Author Spotlight: Developing a Simple and Robust Hepatic Model for Pharmacological and Toxicological Applications

Published on: October 20, 2023

2.0K
Advanced 3D Liver Models for In vitro Genotoxicity Testing Following Long-Term Nanomaterial Exposure08:25

Advanced 3D Liver Models for In vitro Genotoxicity Testing Following Long-Term Nanomaterial Exposure

Published on: June 5, 2020

7.4K

Related Concept Videos

Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test01:22

Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test

In clinical practice, the direct measurement of hepatic blood flow to evaluate liver function presents significant challenges due to the intricate and specialized nature of the necessary techniques. Consequently, healthcare professionals often rely on empirical estimates derived from thorough patient examinations and liver function tests to gauge liver health. Among the tools at their disposal, the Child–Pugh and MELD scoring systems stand out for their ability to categorize and assess...
247
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,...
366
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.
433
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow01:26

Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow

Chronic liver disease significantly impacts drug metabolism due to alterations in hepatic blood flow and enzyme accessibility. This disruption affects the body's pharmacokinetics—the movement and processing of drugs within the system. Key enzymes crucial for metabolizing medications become less accessible, changing how drugs are processed and utilized. Furthermore, liver disease influences the synthesis of plasma proteins, such as albumin and globulins, which play critical roles in drug...
307
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...
2.4K
Pharmacodynamic Models: Direct Effect Model and Indirect Response Model01:29

Pharmacodynamic Models: Direct Effect Model and Indirect Response Model

Pharmacodynamic models are essential tools in understanding the relationship between drug concentrations and their effects on biological systems. By characterizing the dynamics of drug action, these models guide dose selection, optimize therapeutic efficacy, and inform the development of new drugs. Two major classes of pharmacodynamic models include direct effect and indirect response models.Direct Effect ModelsDirect effect models describe the immediate relationship between drug concentration...
80