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

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

Author information

1
Institute for Translational Medicine and Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
2
Oral Surgery and Pharmacology, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
3
Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Quebec, Canada.
4
Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
5
Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.

Abstract

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.

PMID:
30929268
DOI:
10.1002/cpt.1446

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