The aim of our study was to evaluate the selectivity of flurbiprofen and flurbinitroxybutylester for inhibition of the cyclooxygenase activity of prostaglandin endoperoxide synthase-2 vs. prostaglandin endoperoxide synthase-1 in human blood monocytes and platelets, respectively. In whole brood, flurbiprofen was approximately 10-fold more potent than flurbinitroxybutylester to inhibit the cyclooxygenase activity of platelet prostaglandin endoperoxide synthase-1 (IC50 μM: 0.90 ± 0.27 vs. 10.70 ± 5, mean ± S.D., P < 0.05). In contrast, the 2 compounds were equipotent to inhibit prostaglandin endoperoxide synthase-2 cyclooxygenase activity in whole blood (IC50 μM: 0.90 ± 0.25 vs. 0.80 ± 0.35) or isolated monocytes (IC50 μM: 0.03 ± 0.02 vs. 0.03 + 0.02). Neither fIurbiprofen nor flurbinitroxybutylester (0.28-112 μM) affected prostaglandin endoperoxide synthase isozyme expression by lypopolysaccharide-stimulated monocytes. In whole blood, flurbinitroxybutylester was slowly converted to flurbiprofen and this in turn could 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 synthase-1. Whether this effect will result in a reduced risk of gastrointestinal toxicity remains to be studied in man.
Effects of flurbiprofen and flurbinitroxybutylester on prostaglandin endoperoxide synthases
PATRIGNANI, Paola
1996-01-01
Abstract
The aim of our study was to evaluate the selectivity of flurbiprofen and flurbinitroxybutylester for inhibition of the cyclooxygenase activity of prostaglandin endoperoxide synthase-2 vs. prostaglandin endoperoxide synthase-1 in human blood monocytes and platelets, respectively. In whole brood, flurbiprofen was approximately 10-fold more potent than flurbinitroxybutylester to inhibit the cyclooxygenase activity of platelet prostaglandin endoperoxide synthase-1 (IC50 μM: 0.90 ± 0.27 vs. 10.70 ± 5, mean ± S.D., P < 0.05). In contrast, the 2 compounds were equipotent to inhibit prostaglandin endoperoxide synthase-2 cyclooxygenase activity in whole blood (IC50 μM: 0.90 ± 0.25 vs. 0.80 ± 0.35) or isolated monocytes (IC50 μM: 0.03 ± 0.02 vs. 0.03 + 0.02). Neither fIurbiprofen nor flurbinitroxybutylester (0.28-112 μM) affected prostaglandin endoperoxide synthase isozyme expression by lypopolysaccharide-stimulated monocytes. In whole blood, flurbinitroxybutylester was slowly converted to flurbiprofen and this in turn could 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 synthase-1. Whether this effect will result in a reduced risk of gastrointestinal toxicity remains to be studied in man.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
