Bilirubin NSAIDs

As the protein binding of most NSAIDs is very high, raised bilirubin and/or low albumin levels could increase the free fraction of NSAIDs available for pharmacological activity. 

All NSAIDs are highly protein bound and increased levels of free drug may occur in the presence of a raised bilirubin, because it can displace the bound drug from albumin. 

NSAIDs should be avoided in decompensated cirrhotic patients because of the potential for impaired metabolism and increases in the level of unbound drug due to low albumin and high bilirubin, but more importantly NSAIDs should be avoided because of their unfavourable side-effect profile (see details in Patient 3). 

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. 

---