CYP450 polymorphisms and clinical pharmacogenetics of ibuprofen after lower third molar extraction

Autor(es):Mostrar menos -

Weckwerth, Giovana M. ^[1] ; Dionisio, Thiago J. ^[1] ; Costa, Yuri M. ^[2] ; Colombini-Ishiquiriama, Bella L. ^[3] ; Oliveira, Gabriela M. ^[1] ; Torres, Elza A. ^[1] ; Bonjardim, Leonardo R. ^[1] ; Calvo, Adriana M. ^[1] ; Moore, Troy ^[4] ; Absher, Devin M. ^[5] ; Santos, Carlos F. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Biol Sci, Bauru Sch Dent, Discipline Pharmacol, Alameda Dr Octavio Pinheiro Brisolla 9-75, BR-17012901 Bauru, SP - Brazil

^[2] Univ Estadual Campinas, Dept Physiol Sci, Piracicaba Dent Sch, Piracicaba, SP - Brazil

^[3] Univ Sao Paulo, Dept Pediat Dent Orthodont & Community Hlth, Bauru Sch Dent, Bauru, SP - Brazil

^[4] Kailos Genet Inc, Huntsville, AL - USA

^[5] HudsonAlpha Inst Biotechnol, Huntsville, AL - USA

• Tipo de documento: Artigo Científico
• Fonte: EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY; v. 77, n. 5 NOV 2020.
• Citações Web of Science: 0

Resumo

Purpose This study hypothesized that drugs accumulate in the bloodstream of poor-metabolizing patients and may have more adverse effects and different pain perceptions and aimed to investigate the influence of CYP450 polymorphisms on acute postoperative pain, swelling, and trismus controlled by ibuprofen (600 mg) in 200 volunteers after dental extraction. In addition, surgical outcomes can determine pain, edema, and trismus and indicate inflammatory reactions after oral surgeries. Methods Genetic sequencing was performed to identify CYP450 polymorphisms and the surgical parameters evaluated: pre and postoperative swelling, trismus, and temperature; self-reported postoperative pain with visual analog scale (VAS); rescue medication consumed; and severity of adverse reactions. Results A multiple linear regression model with independent variables {[}single nucleotide polymorphisms (SNPs), BMI (body mass index), duration, and difficulty of surgery] and dependent variables {[}postoperative pain by sum of pain intensity difference (SPID), trismus, and swelling] was used for analysis. The duration of surgery was a predictor for pain at 8 h and 96 h after surgery, and BMI was a predictor for both swelling and trismus on the 2nd postoperative day. When evaluating CYP2C8 and C9 genotyped SNPs, it was observed that normal metabolizers showed higher pain levels than the intermediate/poor metabolizers on the postoperative periods as compared with time 0 h. In another analysis, the poor metabolizers for CYP2C8 and C9 presented lower levels of postoperative pain after 8 h and used rescue medication earlier than normal metabolizers. Conclusion Ibuprofen 600 mg was very effective in controlling inflammatory pain after lower third molar surgeries, without relevant adverse reactions; although in a very subtle way, patients with poor metabolism had higher levels of pain in the first hours, and no longer after 8 h, and used pain relief medication earlier. (AU)

• Processo FAPESP: 16/12671-5 - Farmacogenética clínica dos enantiômeros do ibuprofeno após exodontias de terceiros molares inferiores
• Beneficiário: Giovana Maria Weckwerth
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 18/04157-5 - Farmacogenética clínica dos enantiômeros do ibuprofeno após exodontias de terceiros molares inferiores
• Beneficiário: Giovana Maria Weckwerth
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado