Related Experiment Video
Updated: May 25, 2026

An All-Human Hepatic Culture System for Drug Development Applications
Published on: October 20, 2023
Mechanistic modeling of drug elimination by the liver using local volume averaging method
M Izadifar1, O D Baik, J Alcorn
1Division of Biomedical Engineering, College of Engineering, University of Saskatchewan, Saskatoon, SK, Canada. mohammad.izadifar@ usask.ca
Abstract:
Local volume averaging method and local mass (drug) equilibrium were used for developing a mathematical model for transient drug transport and elimination in the liver. Taking into account the liver porosity and tortuosity, physio-chemical properties of the drug, the drug effective diffusivity, dispersion, convection, local plasma-hepatocyte equilibrium and hepatocellular drug metabolism, the governing partial differential equation was developed and numerically solved to describe a transient drug transfer and elimination across the liver following intravenous (IV) administration. The predicted values of hepatic clearance and bioavailability had very good agreement with the reported observations for different drugs. Unlike the well-stirred, parallel tube and dispersion models of hepatic clearance, the proposed mechanistic model is able to predict the drug concentration gradient across the liver with time and position in very dynamic conditions associated with drug absorption process in the intestine.
Related Concept Videos
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
A recent model describes pravastatin's hepatobiliary excretion, mediated...
Drug Distribution as One-Compartment Model and Elimination by Nonlinear Pharmacokinetics: Overview
For instance, consider the metabolism of sodium salicylate. This compound is metabolized into two distinct substances: a glucuronide and a glycine conjugate. The rate of conjugation depends on...
One-Compartment Open Model for IV Bolus Administration: Estimation of Elimination Rate Constant, Half-Life and Volume of Distribution
Parameters Affecting Nonlinear Elimination: Zero-Order Input, First-Order Absorption and Two-Compartment Model
When a drug is administered through a constant intravenous infusion and eliminated via nonlinear pharmacokinetics, it follows zero-order input. For example, oral drugs undergo first-order absorption upon administration and are eliminated through nonlinear pharmacokinetics.
In the case of subcutaneously administered drugs,...
Three-Compartment Open Model
One-Compartment Open Model: Urinary Excretion Data and Determination of k

