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Pharmacokinetics of naproxen, celecoxib and meloxicam and the validation of the extraction methodology in saliva samples by LC MS/MS

Grant number: 20/04734-2
Support type:Scholarships in Brazil - Master
Effective date (Start): May 01, 2020
Effective date (End): November 30, 2021
Field of knowledge:Biological Sciences - Pharmacology - Clinical Pharmacology
Principal researcher:Adriana Maria Calvo
Grantee:Nelson Leonel Del Hierro Polanco
Home Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil
Associated research grant:17/12725-0 - Model of pharmakinetics/pharmacodynamics (PK/PD) on the influence of P450 genetic polymorphism (CYP2C9) of non-steroidal anti-inflammatory drugs and main metabolics from saliva samples through LCMS/MS and its role on prescription personalization, AP.JP


The use of saliva samples in pharmacokinetics and bioequivalence studies has been successfully studied since the middle of the last century, in addition to being an excellent means of controlling drug abuse, monitoring patients who make chronic use of drugs, especially those in which the concentration range is very narrow, drug monitoring in children due to the ease of obtaining samples and also in pharmacogenetic studies. The concentration found in saliva corresponds to the free or unbound fraction of the vast majority of drugs, this being the most important value when studying the pharmacological or toxic action of a drug. This concentration is more reliable when dealing with drugs that do not ionize at normal plasma pH. Due to the lower cost, greater patient compliance, the advantage of taking the samples in your own home, in addition to being a non-invasive method, with no risk of contamination, saliva samples are much simpler to collect than those performed in plasma, which often cause bruising, discomfort or are not performed due to fear of patients considering the multiple collections required in pharmacokinetic studies. The drugs chosen in this project were based on the representation of several subclasses of NSAIDs, being, naproxen, a derivative of propionic acid, non-selective for COX-2; meloxicam, from the oxicans group, partially selective for COX-2; and, celecoxib, a COX-2 selective NSAID. All the proposed drugs are widely used in clinical dental practice, and are of great interest to our area of expertise. It is worth mentioning that 30 volunteers will participate in this project, 15 individuals not mutated and 15 mutated for CYP2C9, who will compose the main research sample, in an attempt to confirm the hypothesis of the Jovem Pesquisador's main project that subjects with the polymorphic genotype in the gene CYP2C9 present slower metabolism and less effective action of the NSAIDs in question in controlling inflammatory signs. Furthermore, these people must be affected by more adverse effects compared to those with wild genotype. (AU)

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