Oxaprozin disposition in renal disease

Area of Science:

• Pharmacokinetics
• Nephrology
• Rheumatology

Background:

• Oxaprozin is a nonsteroidal anti-inflammatory drug (NSAID) used for pain relief.
• Renal impairment can alter drug disposition and efficacy.
• Understanding oxaprozin's behavior in renal disease is crucial for safe and effective dosing.

Purpose of the Study:

• To investigate the effects of renal disease on the pharmacokinetic disposition of oxaprozin.
• To determine how renal impairment and hemodialysis influence oxaprozin's clearance, volume of distribution, and half-life.
• To provide evidence-based dosing recommendations for azotemic patients.

Main Methods:

• Study included 15 subjects: normal, renally impaired, and undergoing hemodialysis.
• Assessed oral dose clearance (Cloral), volume of distribution at steady-state (Vssd), and elimination half-life (t 1/2).
• Measured mean fraction of unbound oxaprozin in plasma (fup) and calculated unbound drug kinetic parameters (Clint, Vssdu).

Main Results:

• Cloral, Vssd, and t 1/2 did not significantly differ across groups.
• Mean fup increased in renally impaired and hemodialysis groups compared to normal subjects.
• Unbound drug clearance (Clint) and volume of distribution (Vssdu) were reduced in azotemic patients.
• Decreased plasma and tissue binding of oxaprozin observed in azotemia.

Conclusions:

• Renal disease significantly affects oxaprozin's unbound fraction and intrinsic clearance.
• Reduced tissue binding in azotemia leads to a smaller volume of distribution for unbound drug.
• A starting dose of 600 mg once daily is recommended for azotemic patients with rheumatoid arthritis.