Abstract
The goal of this study was to test the hypothesis that NCX-4016 may have broader anti-inflammatory and antithrombotic effects as well as better gastric tolerability than aspirin in humans. NCX-4016 is an aspirin derivative containing a nitric oxide-releasing moiety that prevents platelet activation and modulates tissue factor (TF) expression and cytokine release from lipopolysaccharide (LPS)-stimulated monocytes. This was a blind-observer, placebo-controlled, parallel-group study in which 48 healthy subjects were randomized to receive NCX-4016 800 mg twice a day, NCX-4016 800 mg twice a day plus aspirin 325 mg, aspirin 325 mg, or placebo for 21 days. Similar to aspirin alone, NCX-4016 effectively inhibited platelet aggregation induced by 0.6 mmol/ arachidonic acid, clot-stimulated thromboxane (TX) B2 generation in whole blood, and urinary excretion of 11-dehydro-TXB2. Unlike aspirin alone, the administration of NCX-4016 significantly inhibited TF expression in monocytes stimulated ex vivo with 10 micromol/l LPS (determined by flow-cytometry analysis of TF on CD14 positive cells). NCX-4016 also inhibited the rapid TF expression induced in monocytes by a proteinase activated receptor agonist (thrombin receptor activator protein, ...Continue Reading
References
Oct 17, 1991·The New England Journal of Medicine·R J ClarkeG A FitzGerald
Jul 1, 1995·The Journal of Clinical Investigation·R De CaterinaJ K Liao
Nov 16, 1996·Lancet·UNKNOWN CAPRIE Steering Committee
Feb 4, 1997·Circulation·V ToschiJ J Badimon
Aug 19, 1997·Circulation·F CipolloneA Maseri
Nov 14, 1997·The Journal of Biological Chemistry·A D SchecterM B Taubman
Sep 11, 1998·Nature·L BoringI F Charo
Oct 27, 1998·Circulation·D CorseauxB Jude
Jan 14, 1999·The New England Journal of Medicine·R Ross
Mar 5, 1999·Thrombosis Research·J L WallaceG Cirino
Apr 30, 1999·Gastroenterology·S FiorucciA Morelli
Jun 22, 1999·The New England Journal of Medicine·G D Sloop
May 10, 2000·Circulation·Y Yang, J Loscalzo
Jun 14, 2000·European Journal of Pharmacology·S MomiP Gresele
Aug 16, 2000·Circulation·S KitamotoA Takeshita
Sep 21, 2000·The New England Journal of Medicine·A LanasR Sáinz
Oct 14, 2000·Arteriosclerosis, Thrombosis, and Vascular Biology·E LindmarkA Siegbahn
Jul 5, 2001·Proceedings of the National Academy of Sciences of the United States of America·M Riewald, W Ruf
Oct 19, 2001·British Journal of Pharmacology·P MinuzA Lechi
Dec 26, 2001·The New England Journal of Medicine·F Catella-LawsonG A FitzGerald
Apr 10, 2002·Circulation·John W EikelboomSalim Yusuf
Jun 19, 2002·Circulation·Emiko MoriKeizo Sugimachi
Jul 18, 2002·Nature Reviews. Drug Discovery·John L WallaceStefano Fiorucci
Sep 18, 2002·Circulation·Andreas SchoberChristian Weber
Dec 11, 2002·Circulation·Stefano FiorucciPietro Minuz
Dec 20, 2002·Nature·Peter Libby
Mar 4, 2003·Gastroenterology·Stefano FiorucciAntonio Morelli
Sep 10, 2003·Proceedings of the National Academy of Sciences of the United States of America·Stefano FiorucciAntonio Morelli
Citations
Jul 10, 2009·Current Opinion in Hematology·Galia Spectre, David Varon
Nov 26, 2008·Arthritis Research & Therapy·Angel Lanas
Nov 2, 2006·PLoS Medicine·Isabelle BoutronPhilippe Ravaud
May 23, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Marcin MagierowskiTomasz Brzozowski
Dec 16, 2006·Endothelium : Journal of Endothelial Cell Research·Dimitris TousoulisChristodoulos Stefanadis
Jul 19, 2005·Expert Opinion on Investigational Drugs·Roberto ScatenaBruno Giardina
Nov 1, 2005·Expert Opinion on Investigational Drugs·Brendan J R Whittle
Dec 17, 2011·International Immunopharmacology·Muzammal HussainMuti Ur Rehman
Sep 12, 2006·Cardiovascular Drug Reviews·Paolo Gresele, Stefania Momi
May 17, 2006·British Journal of Pharmacology·Catriona M TurnbullIan L Megson
Nov 3, 2011·Parkinson's Disease·Emma StackAnn Ashburn
Oct 10, 2006·International Journal of Cardiology·Roberto LorussoAndrea Giustina
Sep 26, 2006·International Journal of Cardiology·Charalambos AntoniadesChristodoulos Stefanadis
Nov 16, 2006·Expert Opinion on Therapeutic Targets·Catriona M TurnbullIan L Megson
Jul 9, 2010·Platelets·Ulla DerhaschnigBernd Jilma
Feb 25, 2015·Journal of Gastroenterology·Eleonora DistruttiStefano Fiorucci
Sep 11, 2004·Journal of the American College of Cardiology·Richard I Levin
Nov 8, 2014·PloS One·Noraziah NordinMahmood Ameen Abdulla
Dec 23, 2016·Medicinal Research Reviews·Catarina Pereira-LeiteSalette Reis
Jan 5, 2005·Journal of the American College of Cardiology·Anthony N DemariaSotirios Tsimikas
Apr 3, 2007·British Journal of Pharmacology·M R Miller, I L Megson
Sep 25, 2019·Gut and Liver·Chuan-Guo Guo, Wai K Leung
Jan 8, 2021·Cancer Metastasis Reviews·Kathryn ColeJames E Talmadge
May 18, 2021·Frontiers in Pharmacology·Aleksandra DanielakMarcin Magierowski
Jul 3, 2021·International Journal of Molecular Sciences·Alicja NowaczykGrzegorz Grześk