Effects of flurbiprofen and flurbinitroxybutylester on prostaglandin endoperoxide synthases
| Autor: | M. R. Panara, Paola Patrignani, Maria G. Sciulli, Maria di Giamberardino, Roberto Padovano, Piero Del Soldato, Giovanna Santini, M. T. Rotondo |
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| Rok vydání: | 1996 |
| Předmět: |
Adult
Blood Platelets Male Flurbiprofen Pharmacology Dinoprostone Drug Stability medicine Humans Platelet Cyclooxygenase Inhibitors IC50 Whole blood biology Chemistry Monocyte Anti-Inflammatory Agents Non-Steroidal Biological activity Middle Aged Isoenzymes Thromboxane B2 medicine.anatomical_structure Biochemistry Enzyme inhibitor biology.protein Leukocytes Mononuclear lipids (amino acids peptides and proteins) Female Cyclooxygenase medicine.drug |
| Zdroj: | European journal of pharmacology. 316(1) |
| ISSN: | 0014-2999 |
| Popis: | 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., P0.05). 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. |
| Databáze: | OpenAIRE |
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