Document Detail

Effects of nimesulide, acetylsalicylic acid, ibuprofen and nabumetone on cyclooxygenase-1- and cyclooxygenase-2-mediated prostanoid production in healthy volunteers ex vivo.
MedLine Citation:
PMID:  19152549     Owner:  NLM     Status:  MEDLINE    
: The beneficial actions of non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with inhibition of cyclooxygenase-2 (COX-2), whereas some of their adverse effects are associated mainly with inhibition of COX-1. Selective COX-2 inhibitors reduce the risk of gastrointestinal adverse events, but increase the risk of thromboembolic events pointing to importance of optimal COX-1/COX-2 inhibition in drug safety. We compared the effects of acetylsalicylic acid, ibuprofen, nabumetone and nimesulide on COX-1 and COX-2 pathways in healthy volunteers in an ex vivo set-up using single oral doses commonly used to treat acute pain. In a randomized, double-blind four-phase cross-over study, 15 healthy volunteers were given orally a single dose of either acetylsalicylic acid 500 mg, ibuprofen 400 mg, nabumetone 1 g or nimesulide 100 mg. Blood samples were drawn before and 1, 3, 6, 24 and 48 hr after the drug for the assessment of COX-1 and COX-2 activity. COX-1 activity was measured as thromboxane(2) production during blood clotting and COX-2 activity as endotoxin-induced prostaglandin E(2) synthesis in blood leucocytes. The data show that after a single oral dose these four NSAIDs have different profiles of action on COX-1 and COX-2. As expected, acetylsalicylic acid appeared to be COX-1-selective and ibuprofen effectively inhibited both COX-1 and COX-2. Nabumetone showed only a slight inhibitory effect on COX-1 and COX-2. Nimesulide caused almost complete suppression of COX-2 activity and a partial reduction of COX-1 activity. This confirms the relative COX-2 selectivity of nimesulide.
Markku Kerola; Katriina Vuolteenaho; Outi Kosonen; Hannu Kankaanranta; Seppo Sarna; Eeva Moilanen
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Publication Detail:
Type:  Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Basic & clinical pharmacology & toxicology     Volume:  104     ISSN:  1742-7843     ISO Abbreviation:  Basic Clin. Pharmacol. Toxicol.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2009-01-20     Completed Date:  2009-03-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101208422     Medline TA:  Basic Clin Pharmacol Toxicol     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  17-21     Citation Subset:  IM    
The Immunopharmacology Research Group, Medical School, University of Tampere, and Research Unit, Tampere University Hospital, Tampere, Finland.
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MeSH Terms
Anti-Inflammatory Agents, Non-Steroidal / blood*,  pharmacology*
Aspirin / blood,  pharmacology
Butanones / blood,  pharmacology
Cross-Over Studies
Cyclooxygenase 1 / metabolism*
Cyclooxygenase 2 / metabolism*
Dinoprostone / biosynthesis*,  blood
Dose-Response Relationship, Drug
Double-Blind Method
Ibuprofen / blood,  pharmacology
Sulfonamides / blood,  pharmacology
Thromboxane B2 / biosynthesis,  blood
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Butanones; 0/Sulfonamides; 15687-27-1/Ibuprofen; 363-24-6/Dinoprostone; 42924-53-8/nabumetone; 50-78-2/Aspirin; 51803-78-2/nimesulide; 54397-85-2/Thromboxane B2; EC 1; EC 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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