Pharmacogenetic and Pharmacokinetic Assays from Saliva Samples Can Guarantee Personalized Drug Prescription

Author(s)

Bruna Bolani ^[1] ; Gabriela Moraes Oliveira ^[2] ; Thiago José Dionísio ^[3] ; Flavio Augusto Cardoso Faria ^[4] ; Maria Helena Raposo Fernandes ^[5] ; Carlos Ferreira Santos ^[6] ; Adriana Maria Calvo ^[7]

Affiliation

^[1] University of São Paulo. Bauru School of Dentistry. Department of Biological Sciences - Brasil

^[2] University of São Paulo. Bauru School of Dentistry. Department of Biological Sciences - Brasil

^[3] University of São Paulo. Bauru School of Dentistry. Department of Biological Sciences - Brasil

^[4] University of São Paulo. Bauru School of Dentistry. Department of Biological Sciences - Brasil

^[5] Faculty of Dental Medicine. Laboratory for Bone Metabolism and Regeneration - Portugal

^[6] University of São Paulo. Bauru School of Dentistry. Department of Biological Sciences - Brasil

^[7] University of São Paulo. Bauru School of Dentistry. Department of Biological Sciences - Brasil

• Document type: Journal article
• Source: Brazilian Dental Journal; v. 32, n. 1, p. 3-8, 2021-04-02.

Abstract

Abstract Saliva is widely used for clinical and laboratory analysis. This study proposed to use DNA extracted from saliva for genotyping and pharmacokinetics of piroxicam. A fast and efficient genotyping method was used to determine relevant allelic variants of CYP2C9 (*2 and *3), since genetic factors can influence in non-steroidal anti-inflammatory drugs (NSAIDs) metabolization. DNA Extract All Reagents Kit® was used for DNA extraction and genotyping was performed using TaqMan® GTXpress™ Master Mix, SNP genotyping assays and a Viia7 Real-Time PCR system. Volunteers performed sequential collections of saliva samples before and after taking a single dose of piroxicam (0.25 to 72 h) which were used for pharmacokinetics assays. Piroxicam concentrations were analyzed using LC-MS/MS. Sixty-six percent of volunteers were ancestral homozygous (CYP2C9*1/*1), and 34% showed one or both polymorphisms. Of these 34%, 22 individuals showed CYP2C9*2 polymorphism, 8 CYP2C9*3, and 4 CYP2C9*2/*3. Piroxicam pharmacokinetics were performed in 5 subjects. Areas under the curve (AUC0-t(h*ng/mL)) for CYP2C9*1/*1, *1/*2 and *1/*3 were, respectively, 194.33±70.93, 166 and 303. Maximum concentrations (Cmax(ng/mL)) for these genotypes were respectively 6.46±2.56, 4.3 and 10.2. Saliva sampling was a very effective matrix for both pharmacogenetic and pharmacokinetic tests, ensuring the speed of the procedure and the well-being and agreement of the participants. Once having the knowledge about the slow and fast metabolizers, it is possible to make an adequate prescription in order to avoid the adverse effects of the medication and to guarantee greater analgesic comfort to the patients respectively. (AU)

• FAPESP's process: 09/17851-8 - Influence of cytochrome P450 (CYP2C9) genotype on the clinical efficacy and pharmacokinetics of piroxicam after lower third molar surgery
• Grantee: Adriana Maria Calvo
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 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
• Grantee: Adriana Maria Calvo
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 18/02556-0 - Study of cytochrome P450 (CYP2C9) polymorphyms for pharmacogenetic tests
• Grantee: Bruna Bolani
• Support Opportunities: Scholarships in Brazil - Scientific Initiation