The biochemical selectivity of novel COX-2 inhibitors in whole blood assays of COX-isozyme activity.

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Tacconelli S, Capone ML, Sciulli MG, Ricciotti E, Patrignani P

The biochemical selectivity of novel COX-2 inhibitors in whole blood assays of COX-isozyme activity.

Curr Med Res Opin. 2002;18(8):503-11.

PubMed ID

12564662 [ View in PubMed

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Abstract

We 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-a-vis celecoxib and rofecoxib remains to be established.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Valdecoxib	Prostaglandin G/H synthase 2	Protein	Humans	Yes	Inhibitor	Details