LOCATION OF BINDING-SITES ON IMMOBILIZED HUMAN SERUM-ALBUMIN FOR SOME NONSTEROIDAL ANTIINFLAMMATORY DRUGS

Anti-inflammatory drugs are widely used therapeutic agents and are very often administered with various other drugs. Because they are highly bound to human serum albumin (HSA), interferences between nonsteroidal anti-inflammatory drugs (NSAIDs) and coadministered drugs may arise from their interactions at a binding site on HSA. Although the percentage of binding to HSA is generally accurately determined, the binding sites to which a particular therapeutic agent binds are often unknown. In order to clarify where different classes of NSAIDs bind on the HSA molecule, competition studies were carried out on a HSA-based HPLC column using site I and site II markers as displacing agents. Results show that all the NSAIDs included in the study were affected by site I and site II markers and that a number of drugs had (an) extra binding site(s) not affected by any of the competitors used in the study. Competition data also suggest that binding of NSAIDs at the benzodiazepine site could in fact occur at two separate subsites, as previously observed for benzodiazepines.