Study on enteral nutrient components causing decreased gastric phenytoin absorption

Area of Science:

• Pharmacology
• Gastroenterology
• Nutritional Science

Background:

• Enteral nutrients (ENs) can alter the absorption of phenytoin (PHT), an antiepileptic drug.
• The precise mechanisms behind this interaction and the differential effects of various ENs remain unclear.

Purpose of the Study:

• To investigate the impact of specific enteral nutrients on phenytoin permeability and absorption.
• To elucidate the mechanisms by which ENs affect PHT gastrointestinal absorption.

Main Methods:

• Utilized Caco-2 cell monolayers as a model for human intestinal absorption.
• Assessed PHT permeability in the presence of casein, soy protein, digested variants (G-casein, P-casein, G-soy, P-soy), dextrin, sucrose, and minerals.
• Measured PHT binding rates and transepithelial electrical resistance (TEER) to evaluate effects on intestinal barrier function.

Main Results:

• Casein, digested soy protein (G-soy/P-soy), and dextrin significantly reduced PHT permeability.
• Digested casein (G-casein/P-casein) paradoxically increased PHT permeability and decreased TEER, suggesting disruption of tight junctions.
• High viscosity was observed for casein and dextrin, and high PHT binding to casein was noted.

Conclusions:

• Casein, digested soy protein, and dextrin decrease PHT absorption, likely through physical interactions or viscosity.
• Digested casein impairs PHT absorption by compromising intestinal tight junction integrity.
• Understanding these nutrient-drug interactions is crucial for optimizing PHT therapy with enteral nutrition.