title: Effects of flurbiprofen and flurbinitroxybutylester on prostaglandin endoperoxide synthases.
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 blood, flurbiprofen was approximately 10-fold more potent that flurbinitroxybutylester to inhibit the cyclooxygenase activity of platelet prostaglandin endoperoxide synthase-1 (IC50 microM: 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 microM: 0.90 +/- 0.25 vs. 0.80 +/- 0.35) or isolated monocytes (IC50 microM: 0.03 +/- 0.02). Neither flurbiprofen nor flubinitroxybutylester (0.28-112 microM) affected prostaglandin endoperoxide synthase isozyme expression by lypopolysaccharide-stimulated monocytes. In whole blood, flurbinitroxybutylester was slowly converted to flubiprofen 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.
authors.affiliation: Department of Pharmacology I, University of Chieti G. D'Annunzio School of Medicine, Palazzina delle Scuole di Specializzazione, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Santini
authors.forename: M G
authors.initials: MG
authors.lastname: Sciulli
authors.forename: M R
authors.initials: MR
authors.lastname: Panara
authors.forename: R
authors.initials: R
authors.lastname: Padovano
authors.forename: M
authors.initials: M
authors.lastname: di Giamberardino
authors.forename: M T
authors.initials: MT
authors.lastname: Rotondo
authors.forename: P
authors.initials: P
authors.lastname: Del Soldato
authors.forename: P
authors.initials: P
authors.lastname: Patrignani
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000494:pharmacology*; D001792:Blood Platelets / Q000201:enzymology; D016861:Cyclooxygenase Inhibitors / Q000097:blood* / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis / Q000097:blood; D004355:Drug Stability; D005260:Female; D005480:Flurbiprofen / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D013929:Thromboxane B2 / Q000096:biosynthesis / Q000097:blood
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; C095631:nitroflurbiprofen; D013929:Thromboxane B2; D005480:Flurbiprofen; D015232:Dinoprostone