Pharmacodynamic of cyclooxygenase inhibitors in humans

We provide comprehensive knowledge on the differential regulation of expression and catalysis of cyclooxygenase (COX)-1 and COX-2 in health and disease which represents an essential requirement to read out the clinical consequences of selective and nonselective inhibition of COX-isozymes in humans....

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Published inProstaglandins & other lipid mediators Vol. 82; no. 1; pp. 85 - 94
Main Authors Capone, Marta L., Tacconelli, Stefania, Di Francesco, Luigia, Sacchetti, Andrea, Sciulli, Maria G., Patrignani, Paola
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 2007
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Summary:We provide comprehensive knowledge on the differential regulation of expression and catalysis of cyclooxygenase (COX)-1 and COX-2 in health and disease which represents an essential requirement to read out the clinical consequences of selective and nonselective inhibition of COX-isozymes in humans. Furthermore, we describe the pharmacodynamic and pharmacokinetic characteristics of major traditional nonsteroidal anti-inflammatory drugs (tNSAIDs) and coxibs (selective COX-2 inhibitors) which play a prime role in their efficacy and toxicity. Important information derived from our pharmacological studies has clarified that nonselective COX inhibitors should be considered the tNSAIDs with a balanced inhibitory effect on both COX-isozymes (exemplified by ibuprofen and naproxen). In contrast, the tNSAIDs meloxicam, nimesulide and diclofenac (which are from 18- to 29-fold more potent towards COX-2 in vitro) and coxibs (i.e. celecoxib, valdecoxib, rofecoxib, etoricoxib and lumiracoxib, which are from 30- to 433-fold more potent towards COX-2 in vitro) should be comprised into the cluster of COX-2 inhibitors. However, the dose and frequency of administration together with individual responses will drive the degree of COX-2 inhibition and selectivity achieved in vivo. The results of clinical pharmacology of COX inhibitors support the concept that the inhibition of platelet COX-1 may translate into an increased incidence of serious upper gastrointestinal bleeding but this effect on platelet COX-1 may mitigate the cardiovascular hazard associated with the profound inhibition of COX-2-dependent prostacyclin (PGI 2).
ISSN:1098-8823
DOI:10.1016/j.prostaglandins.2006.05.019