Related Experiment Video
Updated: Apr 21, 2026
08:59
An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
Published on: December 3, 2020
8.9K
An on-chip small intestine-liver model for pharmacokinetic studies
Hiroshi Kimura1, Takashi Ikeda2, Hidenari Nakayama2
1Institute of Industrial Science, the University of Tokyo, Tokyo, Japan Department of Mechanical Engineering, Tokai University, Kanagawa, Japan Core Research for Evolutionary Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo, Japan.
Journal of Laboratory Automation
|November 12, 2014
Summary
This study presents a novel microfluidic device that connects small-scale tissue models of the small intestine, liver, and lung. This organ-to-organ network effectively predicts drug pharmacokinetics in vitro, offering an alternative to animal testing.
Area of Science:
- Biomedical Engineering
- Pharmacology
- Toxicology
Background:
- Conventional cell-based assays struggle to predict pharmacokinetics due to their inability to model multiorgan interactions.
- Micro Total Analysis Systems (MicroTAS) technology offers potential for creating microfluidic networks that mimic the human body's organ-to-organ network.
- Developing in vitro models that accurately reflect in vivo physiological conditions is crucial for drug development.
Purpose of the Study:
- To develop and validate an on-chip small intestine-liver coupled microfluidic model for pharmacokinetic studies.
- To mimic key physiological parameters like circulation, organ volume ratios, and blood flow using microfluidic networks.
- To demonstrate the utility of this model in predicting anticancer drug pharmacokinetics and effects.
Main Methods:
- Constructed a microfluidic network connecting Caco-2 (small intestine), HepG2 (liver), and A549 (lung) cell cultures.
- Mimicked physiological parameters including internal circulation, organ volume ratios, and portal vein/hepatic artery blood flow ratios.
- Utilized anticancer drugs (epirubicine, irinotecan, cyclophosphamide) to test the model's ability to replicate drug effects and interactions.
Main Results:
- The microfluidic device successfully replicated physiological phenomena, including the activity of anticancer drugs on target cells.
- The coupled organ model demonstrated the potential for predicting drug pharmacokinetics by simulating organ-to-organ interactions.
- The assay provided insights into the effects of epirubicine, irinotecan, and cyclophosphamide in a multi-organ context.
Conclusions:
- This on-chip organ model serves as a valuable in vitro tool for predicting human pharmacokinetics.
- The microfluidic system offers a promising alternative to traditional animal testing methods.
- The developed model can generate crucial parameters for in silico physiologically based pharmacokinetic models.
Related Concept Videos
01:16Methods for Studying Drug Absorption: In vitro
827
In vitro experiments are crucial for understanding the transport and absorption of drugs through biological materials. These studies employ varied methods such as the diffusion cell method, the everted sac technique, and the everted ring technique.
The diffusion cell method uses a two-compartment cell, including a donor compartment with the drug solution, which simulates the environment where the drug is applied, and a receptor compartment with a buffer solution, which simulates the environment...
The diffusion cell method uses a two-compartment cell, including a donor compartment with the drug solution, which simulates the environment where the drug is applied, and a receptor compartment with a buffer solution, which simulates the environment...
827
01:09Methods for Studying Drug Absorption: In situ
887
In situ experiments, such as the Doluisio method and Single-Pass Perfusion technique, provide critical insights into drug uptake by simulating in vivo conditions for drug absorption.
The Doluisio method involves perfusing a prepared segment of a rat's small intestine with a solution of radiolabeled drug and a non-absorbable marker. This helps to differentiate between absorbed and non-absorbed drug concentrations. The intestinal segment is connected at both ends using tubing and syringes,...
The Doluisio method involves perfusing a prepared segment of a rat's small intestine with a solution of radiolabeled drug and a non-absorbable marker. This helps to differentiate between absorbed and non-absorbed drug concentrations. The intestinal segment is connected at both ends using tubing and syringes,...
887
01:07Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
385
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,...
A recent model describes pravastatin's hepatobiliary excretion,...
385
01:20Pharmacokinetic Models: Overview
2.8K
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...
There are three primary types of models: empirical, compartment, and physiological. Empirical models, with minimal...
2.8K
01:14Pharmacokinetic–Pharmacodynamic Relationship: Model Components
196
Pharmacokinetic-pharmacodynamic (PK–PD) modeling is essential in drug development and clinical pharmacology. It provides a quantitative framework to predict drug behavior and response over time. This approach integrates pharmacokinetics (PK), which describes the drug's absorption, distribution, metabolism, and excretion, with pharmacodynamics (PD), which characterizes the drug’s biological effects and mechanisms of action.The disposition kinetics of a drug determine its plasma...
196
01:15One-Compartment Open Model for Extravascular Administration: First-Order Absorption Model
751
The first-order absorption model for extravascular administration describes the rate at which a drug is absorbed and eliminated, following the principles of first-order kinetics. This model is vital as it provides a mathematical representation of drug behavior within the body. It also allows for the prediction and interpretation of drug absorption and elimination based on the rate of change in drug concentration over time. This model can be visualized as a plasma concentration-time profile...
751