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An In Vivo Method for Evaluating the Gut-Blood Barrier and Liver Metabolism of Microbiota Products
Published on: October 20, 2018
In vitro methods to study intestinal drug metabolism
Esther G van de Kerkhof1, Inge A M de Graaf, Geny M M Groothuis
1Department of Pharmacokinetics and Drug Delivery, Groningen University Institute for Drug Exploration, Groningen, The Netherlands.
Current Drug Metabolism
|November 6, 2007
Summary
The intestine significantly metabolizes drugs, impacting bioavailability. This review compares various in vitro methods for studying intestinal drug metabolism, aiding researchers in selecting appropriate techniques.
Area of Science:
- Pharmacology and Toxicology
- Drug Metabolism and Pharmacokinetics
- Gastrointestinal Physiology
Background:
- The liver's role in drug metabolism is well-established, but intestinal metabolism is increasingly recognized for its impact on drug bioavailability.
- In vivo studies highlight the significance of intestinal first-pass metabolism and the role of drug transporters.
- Distinguishing hepatic from extrahepatic drug metabolism in vivo presents methodological challenges.
Purpose of the Study:
- To review and compare available in vitro methods for studying intestinal drug metabolism.
- To discuss the advantages and limitations of various intact cell systems, subcellular fractions, and cell lines.
- To summarize the applicability of these methods across species for Phase I/II metabolism, transport, and drug-drug interactions.
Main Methods:
- Intact cell systems: isolated intestinal perfusion, everted sac, Ussing chamber, biopsies, precision-cut slices, primary cells.
- Subcellular fractions: S9 fractions, microsomes.
- Intestinal cell lines: Caco-2, LS180, among others.
Main Results:
- Subcellular fractions and cell lines are effective for studying enzyme-level mechanistic aspects of drug metabolism.
- Isolated intestinal perfusion, everted sac, and Ussing chamber methods are suitable for rapidly metabolized drugs and transporter interactions.
- Biopsies, precision-cut slices, and primary cells are appropriate for studying drug metabolism induction and slowly metabolized drugs.
Conclusions:
- A variety of in vitro methods exist to study intestinal drug metabolism, each with specific strengths and limitations.
- Method selection depends on the research question, including the drug's metabolic rate and the focus on enzymes versus transporters.
- These in vitro models are crucial for understanding drug disposition and predicting in vivo outcomes.
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