Influence of Genotype of CYP2C9 on Clinical Efficacy and Pharmacokinetics of Piroxicam After Lower Third Molar Surgery
Condition: Pain; Other Surgical Procedures; Impacted Third Molar Tooth; Cytochrome P450 CYP2C9 Enzyme Deficiency
MeSH terms: Tooth, Impacted
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      Lower third molars (with high degree of difficulty) surgeries will be performed in Clinical
      Pharmacology Laboratory at the Bauru School of Dentistry - University of São Paulo (FOB-USP),
      which will be provided to patients daily doses of piroxicam 20 mg 4 days. Thus collect data
      related to pain, swelling, trismus, amount of rescue medication required by patients, overall
      assessment and satisfaction about taking medicine, saliva samples for the analysis of the
      pharmacokinetics of the drug, genotyping and phenotyping of the subjects of the research.

      The global clinical evaluation along with genotyping and phenotyping these individuals can
      show us if there is an influence not only in adverse effects, but also in the therapeutic
      effects of the drug in the Brazilian population. Research of this nature are rare in this
      area of Clinical Pharmacogenetics and can be of great help in prescribing these drugs to
      control pain and inflammation.After the removal of third molars will make collecting 6 mL of
      saliva in several post-surgical moments for analysis of the pharmacokinetics of the drug
      piroxicam and 10 mL of saliva for the analysis of genetic material. It is noteworthy that
      this project will initiate the nucleation of a new line of research in college, the first in
      Pharmacogenetics area conducted in FOB / USP.Will be assessed the following parameters in all
      patients after surgery of at least a third lower molar with a high degree of difficulty
      (Annexes 1, 2 and 3): 1) onset and duration of surgery after the administration of the local
      anesthetic, 2) open mouth prior to surgery, on the 2nd day after the surgery and on the 7th
      day after surgery (removal of stitches); 3) measured the facial edema in the second day after
      surgery and on the 7th day after surgery (compared to the measurements obtained before
      surgery); 4) body temperature before surgery, on the 2nd day after the operation and on the
      7th day after surgery (removal of stitches); 5) incidence, type and severity of adverse
      reactions, 6) plug pain (VAS - visual analog scale) filled by patients for 4 days after
      prescription Piroxicam; 7) amount of rescue medication required by patients.

      The comparative analysis of the data, along with data on the pharmacokinetics of the drug,
      genotyping and phenotyping the CYP2C9 gene, provide the basis for evaluation of the influence
      of the gene in clinical efficacy, side effects and need for relief medication required by
      patients after surgery third- molars with a high degree of difficulty, which was prescribed
      as anti-inflammatory piroxicam.
    

Intervention name(s): Piroxicam
Intervention type(s): Drug
Intervention description(s): 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).
Other intervention name(s): Lower third molar surgery; Pharmacogenetics
Intervention MeSH terms: Piroxicam
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Supportive Care
Keywords: Piroxicam; Pharmacogenetic; Lower Third molar