Efficacy of piroxicam for postoperative pain after lower third molar surgery associated with CYP2C8*3 and CYP2C9

Abstract

Objective: Nonsteroidal anti-inflammatory drugs (NSAIDs) are metabolized by the cytochrome P450 enzymes (CYPs), predominantly CYP2C8 and CYP2C9. The aim of this study was to evaluate the possible association of polymorphisms in the CYP2C8*3 and CYP2C9 genes with the clinical efficacy of oral piroxicam (20 mg daily for 4 days) after lower third molar surgeries with regard to postoperative pain, swelling, trismus, adverse reactions, need for rescue medication and the volunteer's overall satisfaction.

Materials and methods: For this purpose, 102 volunteers were genotyped for CYP2C8*3 and CYP2C9 polymorphisms. Briefly, genomic DNA was isolated from saliva collected from volunteers subjected to invasive lower third molar surgeries, and the preoperative, intraoperative and postoperative parameters were collected and analyzed.

Results: An equal amount of piroxicam sufficiently managed postoperative pain and inflammatory symptoms, with visual analog pain scores typically <40 mm for all genotypes investigated. Furthermore, only two out of 102 volunteers heterozygous for CYP2C8*3 and CYP2C9*3 reported adverse side effects.

Conclusion: In general, slow metabolizers of piroxicam, who were volunteers with mutant alleles, were indifferent from normal metabolizers with the wild-type alleles and therefore did not require specialized piroxicam doses to manage postoperative pain and inflammation.

Keywords: CYP2C8; CYP2C9; P450; lower third molar surgery; pharmacogenetics; piroxicam.

Figure 1

CONSORT flowchart.

Figure 2

Postoperative pain scores reported by volunteers. Notes: VAS of self-reported postoperative pain scores after lower third molar surgeries assessed at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 48, 72 and 96 hours. Scores could range from 0 to 100 mm, with larger scores indicating increased pain. The top frame refers to the CYP2C8*3- and the lower frame to CYP2C9-bearing volunteers. Abbreviations: CYP, cytochrome P450; VAS, visual analog scale; mt, mutant; wt, Wild type.