Intestinal Transporter-Associated Drug Absorption and Toxicity

Area of Science:

• Pharmacology and Pharmaceutics
• Gastrointestinal Physiology
• Drug Metabolism and Transport

Background:

• Oral drug administration is the preferred clinical route, but drug absorption is complex.
• Intestinal transporters play a crucial role in the absorption of many, but not all, drugs.
• Heterogeneous transporter expression along the intestine leads to variable drug absorption sites.

Purpose of the Study:

• To summarize current research on human intestinal transporters.
• To discuss transporter expression, localization, function, and regulation.
• To explore the impact on low to medium molecular weight drug absorption.

Main Methods:

• Review of existing scientific literature on intestinal transporters.
• Analysis of transporter roles, including bile acid transport proteins (ASBT, OST-α/β).
• Discussion of drug metabolism-transport interactions and the Biopharmaceutics Drug Disposition Classification System (BDDCS).

Main Results:

• Intestinal transporters significantly influence drug absorption rates and extents.
• Bile acid transport proteins and drug metabolism synergistically affect drug disposition.
• The BDDCS model aids in predicting transporter effects on drug absorption.

Conclusions:

• Understanding intestinal transporter characteristics is vital for predicting oral drug absorption.
• Factors like drug-drug interactions, gut microbiota, and bile salt toxicity contribute to intestinal drug-induced toxicity.
• Further research into transporter regulation and function will optimize drug development and patient outcomes.