Pharmacodynamic of cyclooxygenase inhibitors in humans

Prostaglandins Other Lipid Mediat. 2007 Jan;82(1-4):85-94. doi: 10.1016/j.prostaglandins.2006.05.019. Epub 2006 Jul 3.


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 (PGI2).

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Biomarkers
  • Blood Platelets / enzymology
  • Cyclooxygenase 1 / biosynthesis*
  • Cyclooxygenase 2 / biosynthesis*
  • Cyclooxygenase Inhibitors / pharmacokinetics
  • Cyclooxygenase Inhibitors / pharmacology*
  • Endothelium, Vascular / enzymology
  • Gastric Mucosa / enzymology
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Therapeutic Equivalency


  • Anti-Inflammatory Agents, Non-Steroidal
  • Biomarkers
  • Cyclooxygenase Inhibitors
  • Cyclooxygenase 1
  • Cyclooxygenase 2