Selective inhibition of human cyclo-oxygenase-2 by meloxicam

Human cyclo-oxygenase-1 (hCOX-1) and-2 were expressed in stable transfected COS A.2 cells and in insect cells using a Sf9 baculovirus expression system. Inhibition of COX activity was examined using both whole cell and microsomal assays. Ibuprofen, naproxen, 6-MNA, diclofenac and indomethacin were selective for hCOX-1 or were equipotent inhibitors for COX-1 and COX-2. Piroxicam was equally inhibitory for both enzymes in the whole cell assay while it preferentially inhibited hCOX-2 in the microsomal assay. However, maximal inhibition of hCOX-2 by piroxica plateaued at 60%. Nimesulide was equipotent in the whole-cell assay but was five-fold selective for hCOX-2 in the microsomal assay. Meloxicam preferentially inhibited hCOX-2 in the whole cell assay at concentrations of 0.01 to 1 μmol/L but was an equipotent inhibitor of both enzymes at higher concentrations. In the microsomal assay, meloxicam exhibited high selectivity for hCOX-2 (75-fold). The preferential inhibition of hCOX-2 by meloxicam may explain the favourable gastrointestinal profile observed for meloxicam compared with other NSAIDs.