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

Weckwerth, Giovana Maria; Dionísio, Thiago José; Costa, Yuri Martins; Colombini-Ishiquiriama, Bella L.; Oliveira, Graça; Torres, Elza Araujo; Bonjardim, Leonardo Rigoldi; Calvo, Adriana Maria; Moore, Troy; Absher, Devin; Santos, Carlos

doi:10.1007/s00228-020-03046-0

Cited by 6 publications

(7 citation statements)

References 35 publications

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“…In a randomized controlled trial assessing the ibuprofen analgesic efficacy after dental surgery in 43 patients conducted by Saiz-Rodríguez et al [37], a trend toward a greater pain score reduction 6 h after ibuprofen intake was observed in the CYP2C9 PMs compared with the intermediate (IM) or normal (NM) metabolizers was observed. However, no statistically significant impact of the CYP2C9 and CYP2C8 phenotypes in the pain reduction measures was found, which is in concordance with the data observed by Weckwerth et al on 200 patients after lower third molar extraction [38]. In addition, Jaja et al [39] indicated that emergency department visits due to severe pain episodes in 165 sickle cell disease patients receiving NSAIDs including 50 patients receiving ibuprofen were related to the CYP2C9 phenotypes.…”

Section: Ibuprofensupporting

confidence: 83%

Pharmacogenetics and Pain Treatment with a Focus on Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Antidepressants: A Systematic Review

et al. 2022

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Background: This systematic review summarizes the impact of pharmacogenetics on the effect and safety of non-steroidal anti-inflammatory drugs (NSAIDs) and antidepressants when used for pain treatment. Methods: A systematic literature search was performed according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines regarding the human in vivo efficacy and safety of NSAIDs and antidepressants in pain treatment that take pharmacogenetic parameters into consideration. Studies were collected from PubMed, Scopus, and Web of Science up to the cutoff date 18 October 2021. Results: Twenty-five articles out of the 6547 initially detected publications were identified. Relevant medication–gene interactions were noted for drug safety. Interactions important for pain management were detected for (1) ibuprofen/CYP2C9; (2) celecoxib/CYP2C9; (3) piroxicam/CYP2C8, CYP2C9; (4) diclofenac/CYP2C9, UGT2B7, CYP2C8, ABCC2; (5) meloxicam/CYP2C9; (6) aspirin/CYP2C9, SLCO1B1, and CHST2; (7) amitriptyline/CYP2D6 and CYP2C19; (8) imipramine/CYP2C19; (9) nortriptyline/CYP2C19, CYP2D6, ABCB1; and (10) escitalopram/HTR2C, CYP2C19, and CYP1A2. Conclusions: Overall, a lack of well powered human in vivo studies assessing the pharmacogenetics in pain patients treated with NSAIDs or antidepressants is noted. Studies indicate a higher risk for partly severe side effects for the CYP2C9 poor metabolizers and NSAIDs. Further in vivo studies are needed to consolidate the relevant polymorphisms in NSAID safety as well as in the efficacy of NSAIDs and antidepressants in pain management.

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Section: Ibuprofensupporting

confidence: 83%

Pharmacogenetics and Pain Treatment with a Focus on Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Antidepressants: A Systematic Review

et al. 2022

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“…Briefly, 210 adults (≥18 years old) out of 300 were selected to participate in this study of unilateral lower third molar extraction after analysis of their panoramic radiograph (Weckwerth et al, 2016;Simoneti et al, 2018;Weckwerth et al, 2020), according to dental indications, such as orthodontic, endodontic and periodontal problems. All volunteers should have similar lower third molar position and similar degree of impaction according to Pell and Gregory's classification in order to provide similar tissue trauma during surgery (Simoneti et al, 2018); this information can be assessed on Table 1.…”

Section: Registration and Study Designmentioning

confidence: 99%

“…All costs of this research were funded by the São Paulo Research Foundation (FAPESP-Brazil). Dental surgeries were performed from December 2016 through July 2018 at the Clinical of Pharmacology and Physiology Laboratory (LAFFIC) at the Bauru School of Dentistry (FOB), University of São Paulo (USP), Bauru, SP, Brazil, by the same dental surgeon (GMW), using a worldwide standardized (Trindade et al, 2011;Calvo et al, 2012;Weckwerth et al, 2016;Zupelari-Goncalves et al, 2017;Weckwerth et al, 2020), in which the amount of the local anesthetic used (4% articaine with 1:200,000 epinephrine), the duration and the surgical trauma of the operated volunteers were standardized. The side to be operated (right or left) was determined randomly (http://www.randomization.com, number: 20434).…”

Section: Surgery Intervention and Assessmentsmentioning

confidence: 99%

“…Lower third molar extraction model, in addition to allowing the evaluation of the efficacy of analgesic and anti-inflammatory drugs, enables the study of acute pain seen from other important angles that can contribute to the understanding of this multifactorial phenomenon called pain. (Cooper and Beaver, 1976;Akbulut et al, 2014;Silva de Oliveira et al, 2016;Degirmenci and Yalcin, 2019;Weckwerth et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Multifocal Analysis of Acute Pain After Third Molar Removal

et al. 2021

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Background: To analyze the pain modulation capacity profile in a Brazilian population, the relationship between opioid receptor (OPRM1) and Catechol-O-methyltransferase (COMT) 1polymorphisms and pain modulation capacity was determined through preoperative pain modulation tests and acute postoperative pain control evaluation, swelling, and trismus in 200 volunteers undergoing lower third molar removal.Methods: Psychologic and clinical parameters were measured. Patient DNA was sequenced for single nucleotide polymorphisms in OPRM1 and COMT, and the salivary concentration of interleukin (IL)-2 (IL)-6, interferon (IFN)-γ and tumor necrosis factor (TNF)-α was evaluated. Primary outcomes were the influence of all predictors on the fluctuation of pain intensity using a visual analogue scale (VAS), and swelling and trismus on the 2nd and 7th postoperative days. Preoperative pain modulation capacity (CPM), pain catastrophizing scale (PCS), body mass index (BMI), and surgery duration and difficulty were evaluated.Results: Salivary concentration of IFN-γ and IL-2 as well as the duration of surgery influenced the fluctuation of postoperative pain in the VAS, and in the sum of the differences in pain intensity test at 8, 48, and 96 h. BMI influenced swelling, while both BMI and COMT haplotype influenced trismus on the 2nd postoperative day.Conclusion: Polymorphisms in COMT, salivary concentrations of IL-2 and IFN-γ, BMI, and duration of surgery were predictors for pain fluctuation, swelling, and trismus on the 2nd day after lower third molar extraction. This therapy was effective in controlling inflammatory symptomatology after lower third molar extraction and ibuprofen was well tolerated by patients.Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT03169127.

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“…According to the statistics, about 90% of drugs biotransformation need to go through the CYP system, meaning that CYP enzyme is the main prerequisite for the biological transformation, and difference enzymes are controlled by genetic diversity. The metabolic pathways and metabolites of drugs may be different in vitro and in vivo, and polymorphisms are an important characteristic of CYP enzymes, leading to the individual differences in drug reactions [ 28 , 29 ]. The content and activity of CYP enzymes can be affected by different agent, which can affect the metabolism, continuously cause metabolic drug interactions.…”

Section: Introductionmentioning

confidence: 99%

Kinetic Characteristics of Curcumin and Germacrone in Rat and Human Liver Microsomes: Involvement of CYP Enzymes

Zhou

et al. 2022

Molecules

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Curcumin and germacrone, natural products present in the Zingiberaceae family of plants, have several biological properties. Among these properties, the anti-NSCLC cancer action is noteworthy. In this paper, kinetics of the two compounds in rat liver microsomes (RLMs), human liver microsomes (HLMs), and cytochrome P450 (CYP) enzymes (CYP3A4, 1A2, 2E1, and 2C19) in an NADPH-generating system in vitro were evaluated by UP-HPLC–MS/MS (ultrahigh-pressure liquid chromatography–tandem mass spectrometry). The contents of four cytochrome P450 (CYP) enzymes, adjusting by the compounds were detected using Western blotting in vitro and in vivo. The t1/2 of curcumin was 22.35 min in RLMs and 173.28 min in HLMs, while 18.02 and 16.37 min were gained for germacrone. The Vmax of curcumin in RLMs was about 4-fold in HLMs, meanwhile, the Vmax of germacrone in RLMs was similar to that of HLMs. The single enzyme t1/2 of curcumin was 38.51 min in CYP3A4, 301.4 min in 1A2, 69.31 min in 2E1, 63.01 min in 2C19; besides, as to the same enzymes, t1/2 of germacrone was 36.48 min, 86.64 min, 69.31 min, and 57.76 min. The dynamic curves were obtained by reasonable experimental design and the metabolism of curcumin and germacrone were selected in RLMs/HLMs. The selectivities in the two liver microsomes differed in degradation performance. These results meant that we should pay more attention to drugs in clinical medication–drug and drug–enzyme interactions.

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

Cited by 6 publications

References 35 publications

Pharmacogenetics and Pain Treatment with a Focus on Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Antidepressants: A Systematic Review

Pharmacogenetics and Pain Treatment with a Focus on Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Antidepressants: A Systematic Review

Multifocal Analysis of Acute Pain After Third Molar Removal

Kinetic Characteristics of Curcumin and Germacrone in Rat and Human Liver Microsomes: Involvement of CYP Enzymes

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