Microscopic view of intestinal villi with a mini-Ussing chamber illustrating drug transport and metabolism.

Unlock Faster Drug Absorption: The Mini-Ussing Chamber Revolution

Mira Elwood in Health & Wellness December 2025 • 4 min read.

"Simultaneous prediction of intestinal absorption and metabolism with a new approach for better drug development."

Oral bioavailability is key to successful drug development, depending on factors such as intestinal cell permeability (Fa), gut metabolism (Fg), and liver metabolism (Fh). A drug's ability to be absorbed is generally impacted by its physicochemical properties, including molecular weight, lipophilicity, and solubility, as well as intestinal enzymes and transporters.

Enzymes and transporters, such as CYP3A4 and P-gp, are known to lower Fa × Fg in humans. The differentiation of Fa from Fa × Fg is critical for identifying appropriate clinical candidates from a human oral absorbability standpoint. Caco-2 cell monolayers, transfected cell lines, and subcellular fractions of the intestinal epithelium are effective in vitro models for understanding intestinal disposition processes like uptake, transporter-mediated transport, and metabolism.

The goal of this research was to use the transport index (TI) of midazolam (a BCS class 1 compound) and nifedipine (a BCS class II compound) in the presence and absence of ketoconazole (a CYP3A inhibitor) to assess the effect of intestinal metabolism on Fa x Fg quantitatively.

What is the Mini-Ussing Chamber System?

Microscopic view of intestinal villi with a mini-Ussing chamber illustrating drug transport and metabolism.

The Ussing chamber system is a powerful experimental setup used to simultaneously measure membrane permeability and enzyme/transporter interactions. It can also be used with human intestinal tissues. We previously introduced the transport index (TI) value, which can correctly predict human Fa by using small intestinal tissues from dogs and rats in mini-Ussing chambers, and showed a strong correlation with human data. This system has the advantage of accounting for changes in drug solubility during incubations as well as drug accumulation in tissues.

In order to improve metabolic activities, larger exposed areas of intestinal tissues were used in comparison to the earlier investigation in order to reduce edge tissue damage. The metabolic activity of intestinal tissues was lower in comparison to that of in vitro studies.

Animal Intestinal Tissues: Rat jejunum tissues were taken from male Sprague-Dawley (SD) rats with ethical approval and were immediately placed in ice-cold transport buffer.
Transport Experiment in Mini-Ussing Chamber: Mini-Ussing chambers were prepared as previously reported. Intestinal tissues were mounted vertically in the chambers after removing the muscle layer. The available permeation area was 0.20 cm², and the solution temperature was kept at 37°C.
Calculation of Transport Index: TI values were used to measure permeability based on the actual drug concentration in the apical compartment of the mini-Ussing chamber system. TI value was defined as the sum of the percent of the dose transported and tissue-accumulated.

TI values were used to estimate the permeability based on the actual drug concentration in the apical compartment in the mini-Ussing chamber system. TI value was defined to be the sum of the percent of the dose transported and tissue-accumulated corrected by the area under the curve (AUC) value of the parent drug in the apical compartment based on the mass balance of tested compound.

Future Implications for Drug Development

The mini-Ussing chamber system can simultaneously predict intestinal absorption and metabolism. Expanding the exposed tissue area improved intestinal metabolism activities. Further studies using P450/P-gp substrates could clarify P-gp's contribution to Fa × Fg, leading to a better understanding of metabolic enzymes and efflux transporters.

About this Article -

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This article is based on research published under:

DOI-LINK: 10.1016/j.xphs.2018.10.046, Alternate LINK

Title: Simultaneous Prediction Of Intestinal Absorption And Metabolism Using The Mini-Ussing Chamber System

Subject: Pharmaceutical Science

Journal: Journal of Pharmaceutical Sciences

Publisher: Elsevier BV

Authors: Satoshi Kondo, Masateru Miyake

Published: 2019-01-01

Everything You Need To Know

What is the Mini-Ussing Chamber System and what makes it important?

The **Mini-Ussing Chamber system** is an advanced experimental setup designed to measure both membrane permeability and the interactions of enzymes and transporters, offering a significant advantage in drug development. Unlike other in vitro models, it allows for simultaneous assessment of intestinal absorption and metabolism, leading to more accurate predictions of a drug's behavior in the human body. This system can be used with human intestinal tissues, and also accounts for changes in drug solubility during incubations and drug accumulation in tissues. By using the **Mini-Ussing Chamber system**, scientists can simulate the complex processes within the human gut, providing invaluable insights into how drugs are absorbed and metabolized.

What is the Transport Index and how does it work?

The **Transport Index (TI)** value is a crucial metric derived from experiments using the **Mini-Ussing Chamber system**. It is a measurement of permeability based on the actual drug concentration in the apical compartment of the **Mini-Ussing Chamber system**. It helps in the quantitative assessment of intestinal metabolism by taking into account both the amount of drug transported and the amount accumulated in the tissue, corrected by the area under the curve (AUC) value of the parent drug in the apical compartment. The **TI** value is defined as the sum of the percent of the dose transported and tissue-accumulated. It provides a more accurate reflection of a drug's absorption capabilities than simply measuring the amount of drug that passes through a membrane.

Why is oral bioavailability important, and how does the research help with that?

Oral bioavailability, which is the extent and rate at which the active drug enters the systemic circulation, is paramount in successful drug development. Factors like intestinal cell permeability (Fa), gut metabolism (Fg), and liver metabolism (Fh) significantly impact this. The **Mini-Ussing Chamber system** plays a pivotal role by providing a method to measure and predict these factors, allowing researchers to better understand a drug's ability to be absorbed by the body. By using the **Mini-Ussing Chamber system** to simultaneously measure intestinal absorption and metabolism, drug developers can obtain crucial information earlier in the process, leading to more effective and efficient drug design.

What role do enzymes and transporters play in drug absorption?

Intestinal enzymes and transporters, such as **CYP3A4** and **P-gp**, are essential for the absorption process. **CYP3A4** is a major enzyme involved in drug metabolism, while **P-gp** is an efflux transporter that can pump drugs back into the gut, effectively reducing their absorption. The **Mini-Ussing Chamber system** enables the study of how these elements influence drug absorption. The goal of this research was to use the **Transport Index (TI)** of midazolam and nifedipine in the presence and absence of ketoconazole to assess the effect of intestinal metabolism on Fa x Fg quantitatively. By studying these interactions, researchers can predict how well a drug will be absorbed and identify potential issues related to metabolism and transport, thus improving the likelihood of successful drug development.

What are the broader implications of this research for the future?

The research utilizing the **Mini-Ussing Chamber system** carries profound implications for future drug development. By using this system, it is possible to simultaneously predict intestinal absorption and metabolism. Further studies could clarify P-gp's contribution to Fa × Fg, leading to a better understanding of metabolic enzymes and efflux transporters. The use of the **Mini-Ussing Chamber system** represents a significant step forward in the way drugs are designed and tested. It allows for more accurate predictions of a drug's behavior in the human body, leading to faster and more effective drug design. This ultimately can lead to more effective drugs and therapies for a wide range of health conditions.