Giovana M Weckwerth1, Thiago J Dionísio1, Yuri M Costa2, Bella L Colombini-Ishiquiriama3, Gabriela M Oliveira1, Elza A Torres1, Leonardo R Bonjardim1, Adriana M Calvo1, Troy Moore4, Devin M Absher5, Carlos F Santos6. 1. Discipline of Pharmacology, Bauru School of Dentistry, Department of Biological Sciences, University of São Paulo, Alameda Dr. Octávio Pinheiro Brisolla, 9-75, Bauru, SP, 17012-901, Brazil. 2. Piracicaba Dental School, Department of Physiological Sciences, University of Campinas, Piracicaba, SP, Brazil. 3. Bauru School of Dentistry, Department of Pediatric Dentistry, Orthodontics and Community Health, University of São Paulo, Bauru, SP, Brazil. 4. Kailos Genetics Inc., Huntsville, AL, USA. 5. HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA. 6. Discipline of Pharmacology, Bauru School of Dentistry, Department of Biological Sciences, University of São Paulo, Alameda Dr. Octávio Pinheiro Brisolla, 9-75, Bauru, SP, 17012-901, Brazil. cfsantos@fob.usp.br.
Abstract
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. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov ID (NCT03169127), on March 16th, 2017.
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. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov ID (NCT03169127), on March 16th, 2017.
Authors: Paulo A K Trindade; Fernando P M Giglio; Bella L Colombini-Ishikiriama; Adriana M Calvo; Karin Cristina S Modena; Debora A Ribeiro; Thiago J Dionísio; Daniel T Brozoski; José Roberto P Lauris; Flávio Augusto C Faria; Carlos F Santos Journal: Oral Surg Oral Med Oral Pathol Oral Radiol Date: 2011-08-26
Authors: P Zupelari-Goncalves; G M Weckwerth; A M Calvo; L F Simoneti; T J Dionisio; D T Brozoski; E A Torres; J R P Lauris; F A C Faria; C F Santos Journal: Int J Oral Maxillofac Surg Date: 2017-02-01 Impact factor: 2.789
Authors: P A K Trindade; F P M Giglio; B L Colombini-Ishikiriama; A M Calvo; K C S Modena; D A Ribeiro; T J Dionísio; D T Brozoski; J R P Lauris; F A C Faria; C F Santos Journal: Int J Oral Maxillofac Surg Date: 2010-12-08 Impact factor: 2.789
Authors: Carmen Martínez; Elena García-Martín; Gerardo Blanco; Francisco J G Gamito; José M Ladero; José A G Agúndez Journal: Br J Clin Pharmacol Date: 2005-01 Impact factor: 4.335
Authors: A M Senes; A M Calvo; B L Colombini-Ishikiriama; P Z Gonçalves; T J Dionísio; E Sant'ana; D T Brozoski; J R P Lauris; F A C Faria; C F Santos Journal: J Dent Res Date: 2015-07-22 Impact factor: 6.116
Authors: Adriana M Calvo; Daniel T Brozoski; Fernando P M Giglio; Paulo Z Gonçalves; Eduardo Sant'ana; Thiago J Dionísio; José R P Lauris; Carlos F Santos Journal: Oral Surg Oral Med Oral Pathol Oral Radiol Date: 2012-05-30
Authors: Elena García-Martín; Carmen Martínez; Beatriz Tabarés; Jesús Frías; José A G Agúndez Journal: Clin Pharmacol Ther Date: 2004-08 Impact factor: 6.875
Authors: Carmen Martínez; Gerardo Blanco; José M Ladero; Elena García-Martín; Carlos Taxonera; Francisco G Gamito; Manuel Diaz-Rubio; José A G Agúndez Journal: Br J Pharmacol Date: 2004-01-05 Impact factor: 8.739
Authors: Anthony J Senagore; Bradley J Champagne; Eslam Dosokey; Justin Brady; Scott R Steele; Harry L Reynolds; Sharon L Stein; Conor P Delaney Journal: Am J Surg Date: 2016-11-22 Impact factor: 2.565
Authors: Farzin Zobdeh; Ivan I Eremenko; Mikail A Akan; Vadim V Tarasov; Vladimir N Chubarev; Helgi B Schiöth; Jessica Mwinyi Journal: Pharmaceutics Date: 2022-06-01 Impact factor: 6.525