Influence of genotype of cytochrome P450 (CYP2C9) on the clinical efficacy and pharmacokinetics of Piroxicam after lower third molar surgery

• Grant number: 14/17803-1
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2014
• End date: November 30, 2015
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: Carlos Ferreira dos Santos
• Grantee: Carlos Ferreira dos Santos
• Host Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil

Abstract

Pharmacogenetics is an area of Pharmacology that studies the contribution of genetic factors to individual responses to drugs. This branch of science involves the variability in pharmacodynamics and pharmacokinetics through the study of polymorphisms in genes encoding receptors, as well as in drug metabolism, where this area of Pharmacology has been growing and achievinging its first results with clinical use. The NSAIDS are metabolized by cytochrome P450 (CYP) family, predominantly CYP2C9. The goal of this study is to evaluate the different gene haplotypes for the clinical efficacy of piroxicam after third lower molar surgery for pain, edema and trismus, adverse reactions, need of rescue medication, patient satisfaction regarding the drug and the pharmacokinetics of the drug between the different gene haplotypes for CYP2C9 that are found in this population. Therefore, 100 patients will be genotyped and fenotyped for this gene and their postoperative data will be confronted with the data found in the Brazilian population. For the analysis of the proposed gene, saliva will be collected and serve as a source of genomic DNA. For the molecular analysis, polymerase chain reaction (PCR) with tests validated and produced by Applied Biosystems® will be performed. For the pharmacokinetics, blood and saliva samples will be collected at various times according to protocols available in the literature, and piroxicam concentrations in the samples will be measured by HPLC and mass spectrometer. The analysis of the results will be described with a significance level of 0.05. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ZUPELARI-GONCALVES, P.; WECKWERTH, G. M.; CALVO, A. M.; SIMONETI, L. F.; DIONISIO, T. J.; BROZOSKI, D. T.; TORRES, E. A.; LAURIS, J. R. P.; FARIA, F. A. C.; SANTOS, C. F.. Efficacy of oral diclofenac with or without codeine for pain control after invasive bilateral third molar extractions. International Journal of Oral and Maxillofacial Surgery, v. 46, n. 5, p. 621-627, MAY 2017. (14/17803-1)

CALVO, ADRIANA MARIA; ZUPELARI-GONCALVES, PAULO; DIONISIO, THIAGO JOSE; BROZOSKI, DANIEL THOMAS; FARIA, FLAVIO AUGUSTO; SANTOS, CARLOS FERREIRA. Efficacy of piroxicam for postoperative pain after lower third molar surgery associated with CYP2C8{*}3 and CYP2C9. JOURNAL OF PAIN RESEARCH, v. 10, p. 1581-1589, 2017. (09/17851-8, 14/17803-1)

CALVO, ADRIANA MARIA; SANTOS, GABRIEL MULINARI; DIONISIO, THIAGO JOSE; MARQUES, MARIA PAULA; BROZOSKI, DANIEL THOMAS; LANCHOTE, VERA LUCIA; RAPOSO FERNANDES, MARIA HELENA; CARDOSO FARIA, FLAVIO AUGUSTO; SANTOS, CARLOS FERREIRA. Quantification of piroxicam and 5 `-hydroxypiroxicam in human plasma and saliva using liquid chromatography-tandem mass spectrometry following oral administration. Journal of Pharmaceutical and Biomedical Analysis, v. 120, p. 212-220, FEB 20 2016. (09/17851-8, 15/10198-8, 14/17803-1)

CALVO, ADRIANA MARIA; ZUPELARI-GONCALVES, PAULO; DIONISIO, THIAGO JOSE; BROZOSKI, DANIEL THOMAS; FARIA, FLAVIO AUGUSTO; SANTOS, CARLOS FERREIRA. Efficacy of piroxicam for postoperative pain after lower third molar surgery associated with CYP2C8*3 and CYP2C9. JOURNAL OF PAIN RESEARCH, v. 10, p. 9-pg., 2017-01-01. (14/17803-1, 09/17851-8)

CALVO, ADRIANA MARIA; SANTOS, GABRIEL MULINARI; DIONISIO, THIAGO JOSE; MARQUES, MARIA PAULA; BROZOSKI, DANIEL THOMAS; LANCHOTE, VERA LUCIA; RAPOSO FERNANDES, MARIA HELENA; CARDOSO FARIA, FLAVIO AUGUSTO; SANTOS, CARLOS FERREIRA. Quantification of piroxicam and 5 '-hydroxypiroxicam in human plasma and saliva using liquid chromatography-tandem mass spectrometry following oral administration. Journal of Pharmaceutical and Biomedical Analysis, v. 120, p. 9-pg., 2016-02-20. (14/17803-1, 09/17851-8, 15/10198-8)