Influence of Genotype of CYP2C9 on Clinical Efficacy and Pharmacokinetics of Piroxicam After Lower Third Molar Surgery

Summary

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 achieving its first results with clinical use. The non-steroidal anti-inflammatory (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, 60 patients will be genotyped and phenotyped 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, 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 high pressure liquid chromatography (HPLC) and Liquid chromatography-mass spectrometry (LC MS/MS). The analysis of the results will be described with a significance level of 0.05.

Conditions

• Pain
• Other Surgical Procedures
• Impacted Third Molar Tooth
• Cytochrome P450 CYP2C9 Enzyme Deficiency

Interventions

DRUG

Piroxicam

After extraction of at least one third molar, 100 patients will be treated with Piroxicam (20 mg once daily for 4 days) for pain control, collect the saliva to be genotyped and phenotyped for CYP2C9 (by PCR) and their post-operative notes (pain, swelling, trismus, temperature) will be analyzed. For the pharmacokinetics of piroxicam saliva samples will be collected from 10 of these patients at different times after ingestion of a capsule of 20 mg Piroxicam (before, 1, 2, 3, 4, 5, 6, 8, 11, 24, 48 and 72 hours after ingestion).

Sponsors & Collaborators

• Fundação de Amparo à Pesquisa do Estado de São Paulo

  collaborator OTHER_GOV

• University of Sao Paulo

  lead OTHER

Principal Investigators

• Adriana M Calvo, PhD · Bauru School of Dentistry/University of Sao Paulo

Study Design

Allocation

NA

Purpose

SUPPORTIVE_CARE

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

17 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2012-10-31

Primary Completion

2015-10-31

Completion

2015-12-31