Naproxen disposition in hepatic and biliary disorders

Area of Science:

• Pharmacology
• Hepatology
• Drug Metabolism

Background:

• Naproxen is a common nonsteroidal anti-inflammatory drug (NSAID).
• Hepatic and biliary disorders can significantly affect drug pharmacokinetics.
• Understanding these effects is crucial for safe and effective patient management.

Purpose of the Study:

• To investigate the pharmacokinetics of Naproxen in patients with hepatic and biliary disorders.
• To compare Naproxen's absorption, distribution, and elimination in these patients versus healthy volunteers.
• To determine the impact of liver and bile duct conditions on Naproxen's elimination half-life.

Main Methods:

• Oral administration of a single 250 mg dose of Naproxen.
• Pharmacokinetic analysis in 11 patients with diagnosed hepatic and biliary disorders.
• Comparison of data with established values from healthy volunteers.
• Modeling using an open two-compartment model.

Main Results:

• Naproxen pharmacokinetics were modified in patients compared to healthy individuals.
• Delayed absorption was noted in some patients with cholestasis.
• Diminished drug elimination was observed in most patients due to reduced biotransformation capacity.
• The average plasma half-life of the beta-phase increased from 14.14 hours in healthy volunteers to 20.36 hours in patients.

Conclusions:

• Hepatic and biliary disorders significantly alter Naproxen pharmacokinetics.
• Reduced drug metabolism and elimination capacity in these patients lead to a prolonged half-life.
• Clinical monitoring and potential dose adjustments may be necessary for patients with liver or biliary conditions receiving Naproxen.