Interaction of naproxen with cholestyramine

Area of Science:

• Pharmacology
• Drug Interactions
• Gastroenterology

Background:

• Naproxen is a widely used nonsteroidal anti-inflammatory drug (NSAID).
• Cholestyramine is a bile acid sequestrant primarily used to lower cholesterol levels.
• Potential interactions between these two drugs require investigation due to their common co-administration.

Purpose of the Study:

• To investigate the in vitro and in vivo interaction between naproxen and cholestyramine.
• To quantify the binding affinity of cholestyramine for naproxen.
• To evaluate the pharmacokinetic impact of co-administering cholestyramine on naproxen.

Main Methods:

• In vitro studies to determine naproxen adsorption by cholestyramine resin at varying pH.
• In vivo pharmacokinetic study in eight healthy volunteers.
• Concurrent oral administration of naproxen (250 mg) and cholestyramine (4 g).

Main Results:

• Cholestyramine demonstrated a significant affinity for naproxen, influenced by pH.
• Maximum naproxen adsorption by the resin was approximately 2.2 mM/g.
• Co-administration delayed naproxen's entry into systemic circulation without altering other pharmacokinetic parameters.

Conclusions:

• Cholestyramine significantly interacts with naproxen, primarily by delaying its absorption.
• The binding interaction is pH-dependent, with implications for drug dosing and administration timing.
• While absorption is delayed, other key pharmacokinetic aspects of naproxen remain unaffected.