Competition between COX-2 inhibitors and some other drugs for binding sites on human serum albumin.

Competitive binding of six COX-2 inhibitors (celecoxib, valdecoxib, etoricoxib, parecoxib sodium, meloxicam and nimesulide) in the presence of three categories of drugs: an antidiabetic (gliclazide), antipsychotic (chlorpromazine) and antibiotic (ceftriaxone sodium) were studied by fluorescence spectroscopy. Data are expressed in terms of the percentage of drug bound in the absence and presence of competing drug and change in the percentage of free drug due to competitive binding. The results are discussed in terms of three cases: decrease in the binding of the parent drug; increase in binding; and no effect by the presence of the competing drug. The relative binding affinity of the parent drug and the displacing compound for human serum albumin (HSA) is not the only factor involved in the competitive mechanism. Binding behaviour of individual drugs was analysed, and explanations for different cases based on the competitive displacement, non-competitive interference, conformational changes in the HSA molecule, and independent binding are presented.