Stefania Tacconelli, Marta L Capone, Maria G Sciulli, Emanuela Ricciotti, Paola Patrignani
Division of Pharmacology, Department of Medicine and Center of Excellence on Aging, G. D'Annunzio University School of Medicine, 66013 Chieti, Italy.
Current medical research and opinion 2002We have evaluated the biochemical selectivity of novel cyclo-oxygenase (COX)-2 inhibitors, etoricoxib, valdecoxib, DFU and DFP, vs rofecoxib and celecoxib, using the human whole blood assays of COX-isozyme activity, in vitro. Compounds were incubated with human whole blood samples, allowed to clot for 1 h at 37 degrees C, or stimulated with lipopolysaccharide (10 microg/ml) for 24 h at 37 degrees C. Serum thromboxane (TX) B2 and plasma prostaglandin (PG) E2 levels were measured by specific radioimmunoassays as indices of platelet COX-1 and monocyte COX-2 activity, respectively. Valdecoxib, etoricoxib, DFU and DFP inhibited platelet COX-1 and monocyte COX-2 with the following COX-1/COX-2 IC50 ratios: 61.5, 344, 660 and 1918, respectively. The reference compounds, celecoxib and rofecoxib had corresponding values of 29.6 and 272. In conclusion, a second wave of COX-2 inhibitors with higher biochemical selectivity than the existing coxibs has been developed. Whether their administration will be associated with improved clinical efficacy and/or safety vis-à-vis celecoxib and rofecoxib remains to be established.
Stefania Tacconelli, Marta L Capone, Maria G Sciulli, Emanuela Ricciotti, Paola Patrignani. The biochemical selectivity of novel COX-2 inhibitors in whole blood assays of COX-isozyme activity. Current medical research and opinion. 2002;18(8):503-11
PMID: 12564662
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