EFFECTS OF FLURBIPROFEN AND FLURBINITROXYBUTYLESTER ON PROSTAGLANDIN ENDOPEROXIDE SYNTHASES

The aim of our study was to evaluate the selectivity of flurbiprofen a nd flurbinitroxybutylester for inhibition of the cyclooxygenase activi ty of prostaglandin endoperoxide synthase-2 vs. prostaglandin endopero xide synthase-1 in human blood monocytes and platelets, respectively. In whole blood, flurbiprofen was approximately 10-fold more potent tha n flurbinitroxybutylester to inhibit the cyclooxygenase activity of pl atelet prostaglandin endoperoxide synthase-1 (IC50 mu M: 0.90 +/- 0.27 vs. 10.70 +/- 5, mean +/- S.D., P < 0.05). In contrast, the 2 compoun ds were equipotent to inhibit prostaglandin endoperoxide synthase-2 cy clooxygenase activity in whole blood (IC50 mu M: 0.90 +/- 0.25 vs. 0.8 0 +/- 0.35) or isolated monocytes (IC50 mu M: 0.03 +/- 0.02 vs. 0.03 /- 0.02). Neither flurbiprofen nor flurbinitroxybutylester (0.28-112 m u M) affected prostaglandin endoperoxide synthase isozyme expression b y lypopolysaccharide-stimulated monocytes. In whole blood, flurbinitro xybutylester was slowly convened to flurbiprofen and this in turn coul d influence the extent of inhibition of the cyclooxygenase activity of prostaglandin endoperoxide synthase-1. In conclusion, the addition of a nitroxybutyl moiety to flurbiprofen seems to reduce its capacity to inhibit the cyclooxygenase activity of prostaglandin endoperoxide syn thase-1. Whether this effect will result in a reduced risk of gastroin testinal toxicity remains to be studied in man.