Pharmacokinetics of naproxen overdoses

Area of Science:

• Pharmacology
• Clinical Pharmacology
• Drug Metabolism

Background:

• Previous studies indicated naproxen (600 mg TID) was safe in healthy subjects.
• Higher single doses (500-900 mg) of naproxen showed accelerated renal clearance and nonlinear plasma level responses.

Purpose of the Study:

• To investigate the pharmacokinetics of very high single doses of naproxen (1-4 gm) in healthy subjects.
• To assess the safety and tolerability of supratherapeutic naproxen doses.

Main Methods:

• Administration of single naproxen doses ranging from 1 gm to 4 gm to healthy volunteers.
• Monitoring of plasma naproxen levels and urinary excretion rates.
• Assessment for adverse effects and signs of exceeded drug conjugation or excretion capacity.

Main Results:

• Increased urinary excretion rate of naproxen observed with higher doses.
• Continuation of the previously documented nonlinear plasma level response.
• No adverse effects were reported, and no signs of exceeded drug metabolism or excretion capacity were observed.

Conclusions:

• Healthy subjects tolerated single naproxen doses up to 4 gm without adverse effects.
• The pharmacokinetic profile at high doses is characterized by increased excretion and nonlinear plasma levels.
• The body's capacity to conjugate and excrete naproxen was not exceeded even at these supratherapeutic doses.