Related Experiment Video
Updated: Jul 18, 2026

A Modified Inflammatory Pain Model to Study the Analgesic Effect in Mice
Published on: November 15, 2024
The cyclooxygenase 2 genetic variant -765G>C does not modulate the effects of celecoxib on prostaglandin E2
Carsten Skarke1, Maximilian Reus, Ronald Schmidt
1Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Johann Wolfgang Goethe-University, Frankfurt, Germany.
Objective:
Our objective was to assess the role of the reportedly functional PTGS2 (prostaglandin-endoperoxide synthase 2/cyclooxygenase [COX] 2) promoter mutation -765G>C for the COX-2-inhibiting effects of celecoxib.
Methods:
Twenty healthy carriers of the -765GG genotype and -765CC genotype (n = 10 each) received 200 mg of celecoxib orally. Blood samples were drawn at baseline and at 1, 3, 6, 9, and 24 hours after administration. Plasma concentrations of celecoxib and concentrations of prostaglandin E(2) (PGE(2)) produced by peripheral blood monocytes stimulated ex vivo with bacterial lipopolysaccharide (LPS) were analyzed by liquid chromatography-tandem mass spectrometry. Expression of COX-2 messenger ribonucleic acid and protein expression with and without LPS stimulation were analyzed by real-time polymerase chain reaction and Western blotting, respectively.
Results:
LPS induced PGE(2) production (P < .001), and celecoxib reduced PGE(2) production from 19.3 +/- 7.2 ng/mL at baseline to 7.4 +/- 4.8 ng/mL at 1 hour (P < .001). The effect of celecoxib lasted for 9 hours (repeated-measures ANOVA, P
Conclusion:
The PTGS2 -765G>C single-nucleotide polymorphism does not modulate COX-2 inhibitory effects of celecoxib as assessed by an ex vivo whole blood assay. Thus the results indicate the need for further investigation toward PTGS2 pharmacogenetics-based prescription of celecoxib.
Related Concept Videos
Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes
Drugs for Peptic Ulcer Disease: Prostaglandin Analogs as Mucosal Protective Agents
Non-steroidal anti-inflammatory drugs (NSAIDs) can induce peptic ulcers by inhibiting cyclooxygenase, decreasing...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters