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Clinical Pharmacokinetics of Naproxen

  • Review Article
  • Drug Disposition
  • Published:
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Summary

Naproxen is a stereochemically pure nonsteroidal anti-inflammatory drug of the 2-arylpropionic acid class. The absorption of naproxen is rapid and complete when given orally. Naproxen binds extensively, in a concentration-dependent manner, to plasma albumin. The area under the plasma concentration-time curve (AUC) of naproxen is linearly proportional to the dose for oral doses up to a total dose of 500mg. At doses greater than 500mg there is an increase in the unbound fraction of drug, leading to an increased renal clearance of total naproxen while unbound renal clearance remains unchanged.

Substantial concentrations of the drug are attained in synovial fluid, which is a proposed site of action for nonsteroidal anti-inflammatory drugs. Relationships between the total and unbound plasma concentration, unbound synovial fluid concentration and therapeutic effect have been established.

Naproxen is eliminated following biotransformation to glucuroconjugated and sulphate metabolites which are excreted in urine, with only a small amount of the drug being eliminated unchanged. The excretion of the 6-O-desmethylnaproxen metabolite conjugate may be tied to renal function, as accumulation occurs in end-stage renal disease but does not appear to be influenced by age.

Hepatic disease and rheumatoid arthritis can also significantly alter the disposition kinetics of naproxen. Although naproxen is excreted into breast milk, the amount of drug transferred comprises only a small fraction of the maternal exposure.

Significant drug interactions have been demonstrated for probenecid, lithium and methotrexate.

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Authors and Affiliations

  1. Faculty of Medicine, Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, T2N 4N1, Canada

    Neal M. Davies

  2. Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada

    Keith E. Anderson

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  1. Neal M. Davies
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  2. Keith E. Anderson
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Correspondence to Neal M. Davies.

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Davies, N.M., Anderson, K.E. Clinical Pharmacokinetics of Naproxen. Clin-Pharmacokinet 32, 268–293 (1997). https://doi.org/10.2165/00003088-199732040-00002

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