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Pharmacokinetic Models: Overview

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...

Pharmacokinetic Models: Comparison and Selection Criterion

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.

Model Approaches for Pharmacokinetic Data: Physiological Models

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...

Model Approaches for Pharmacokinetic Data: Distributed Parameter Models

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...

Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance

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,...

Physiological Pharmacokinetic Models: Blood Flow-Limited Versus Diffusion-Limited Models

Physiological Pharmacokinetic Models: Blood Flow-Limited Versus Diffusion-Limited Models

Physiological pharmacokinetic models, often called flow-limited or perfusion models, typically assume a swift drug distribution between tissue and venous blood, creating a rapid drug equilibrium. This premise is based on the idea that drug diffusion is extremely fast, and the cell membrane presents no barrier to drug permeation. In this scenario, where no drug binding occurs, the drug concentration in the tissue equals that of the venous blood leaving the tissue. This greatly simplifies the...

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Author Spotlight: Enhancing Understanding and Treatment Strategies with the NEC-on-a-Chip Model

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Published on: July 28, 2023

Microfluidic gut-axis-on-a-chip models for pharmacokinetic-based disease models.

Raehyun Kim¹, Jong Hwan Sung²

¹Department of Biological and Chemical Engineering, Hongik University, Sejong 30016, Republic of Korea.

Biomicrofluidics

|July 1, 2024

Summary

Developing advanced gut-liver-on-a-chip models improves drug development by better mimicking human physiology. These in vitro systems enhance pharmacokinetic studies and disease modeling for personalized medicine.

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Area of Science:

Biomedical Engineering
Pharmacology
Toxicology

Background:

Traditional animal models have low success rates for predicting human drug responses.
Multi-organ-on-a-chip technology offers advanced in vitro platforms for studying organ interactions.
The gut-liver axis is critical for nutrient absorption, drug metabolism, and immune responses.

Purpose of the Study:

To review the components and functions of the gut-liver axis.
To explore the potential of gut-liver-on-a-chip models for simulating gut-liver interactions.
To discuss future directions for physiologically relevant gut-liver models in drug development and disease research.

Main Methods:

Discussion of key components: gut epithelium, liver cells, and gut microbiota.
Exploration of gut-liver-on-a-chip system designs and capabilities.
Review of applications in pharmacokinetics, drug development, and disease modeling.

Main Results:

Gut-liver-on-a-chip models can replicate complex gut-liver interactions.
These models show promise for improving pharmacokinetic predictions.
Expansion to multi-organ models can further enhance physiological relevance.

Conclusions:

Gut-liver-on-a-chip models are essential for accurate drug development.
These systems can advance the study of liver diseases and personalized treatments.
Future research should focus on creating more complex and physiologically representative models.