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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Brazilian Dental Journal; v. 32, n. 1, p. 3-8, 2021-04-02.

Resumo

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)

• Processo FAPESP: 18/02556-0 - Estudo dos polimorfismos do citocromo P450 (CYP2C9) para ensaios de farmacogenética
• Beneficiário: Bruna Bolani
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 17/12725-0 - Modelo de farmacocinética/farmacodinâmica (PK/PD) na influência do polimorfismo genético do P450 (CYP2C9) de anti-inflamatórios não esteroidais e metabólitos principais a partir de amostras de saliva por LCMS/MS e seu papel na personalização da prescrição
• Beneficiário: Adriana Maria Calvo
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 09/17851-8 - Influência do genótipo do citocromo P450 (CYP2C9) na eficácia clínica e farmacocinética do piroxicam após cirurgias de terceiros molares inferiores
• Beneficiário: Adriana Maria Calvo
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado