Naproxen plasma protein binding

Naproxen Valproate Interaction of little or no clinical significance Displacement from plasma protein binding sites... 

Roughly 80-90% of the salicylate in plasma is bound to proteins, especially albumin, at concentrations encountered clinically the proportion of the total that is bound declines as plasma concentrations increase. Hypoalbuminemia, as may occur in rheumatoid arthritis, is associated with a proportionately higher level of free salicylate in the plasma. Salicylate competes with a variety of compounds for plasma protein binding sites these include thyroxine, triiodothyronine, penicillin, phenytoin, sulfinpyrazone, bilirubin, uric acid, and other NSAIDs such as naproxen. 

Grimaldi R, Lecchini S, Crema F, Perucca E. In vivo plasma protein binding interaction between valproic acid and naproxen. EurJ Drug Metab Pharmacokinet (1984) 9, 359-63. 

There are small changes in serum albumin concentration with age, with concomitant small effects on protein binding of some highly bound drugs such as naproxen, salicylate, and warfarin. For such drugs the free concentration rather than the total plasma concentration is a better predictor of drug dose requirements, particularly for drugs with low therapeutic index (difference between the therapeutic... 

Renal disease (uraemia) may increase the volume of distribution of acidic drugs that extensively bind to plasma albumin (e.g., phenytoin, valproic acid, naproxen, phenylbutazone, furosemide). As decreased protein binding would increase the unbound (free) fraction in the plasma, the therapeutic concentration range (based on total drug concentration) would be lower than the usual... 

---