Variability in the Analgesic Response to Ibuprofen Is Associated With Cyclooxygenase Activation in Inflammatory Pain

Clin Pharmacol Ther. 2019 Sep;106(3):632-641. doi: 10.1002/cpt.1446. Epub 2019 Apr 29.


The mechanisms underlying interindividual variability in analgesic efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) are not well understood. Therefore, we performed pain phenotyping, functional neuroimaging, pharmacokinetic/pharmacodynamic assessments, inflammation biomarkers, and gene expression profiling in healthy subjects who underwent surgical extraction of bony impacted third molars and were treated with ibuprofen (400 mg; N = 19) or placebo (N = 10). Analgesic efficacy was not associated with demographic or clinical characteristics, ibuprofen pharmacokinetics, or the degree of cyclooxygenase inhibition by ibuprofen. Compared with partial responders to ibuprofen (N = 9, required rescue medication within the dosing interval), complete responders (N = 10, no rescue medication) exhibited greater induction of urinary prostaglandin metabolites and serum tumor necrosis factor-α and interleukin 8. Differentially expressed genes in peripheral blood mononuclear cells were enriched for inflammation-related pathways. These findings suggest that a less pronounced activation of the inflammatory prostanoid system is associated with insufficient pain relief on ibuprofen alone and the need for additional therapeutic intervention.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Double-Blind Method
  • Female
  • Humans
  • Ibuprofen / pharmacology*
  • Ibuprofen / therapeutic use
  • Inflammation Mediators / metabolism
  • Male
  • Pain, Postoperative / drug therapy*
  • Phenotype
  • Prostaglandin-Endoperoxide Synthases / drug effects*
  • Transcriptome
  • Young Adult


  • Anti-Inflammatory Agents, Non-Steroidal
  • Inflammation Mediators
  • Prostaglandin-Endoperoxide Synthases
  • Ibuprofen