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.
Piracicaba Dental School, Department of Physiological Sciences, University of Campinas, Piracicaba, SP, Brazil.
Eur J Clin Pharmacol. 2021 May;77(5):697-707. doi: 10.1007/s00228-020-03046-0. Epub 2020 Nov 17.
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.
目的：本研究假设药物在代谢不良患者的血液中积累，可能会产生更多的不良反应，并对疼痛感知产生不同的影响，并旨在研究 CYP450 多态性对 200 名接受拔牙术后志愿者的布洛芬（600mg）控制下的急性术后疼痛、肿胀和牙关紧闭的影响。此外，手术结果可以确定疼痛、肿胀和牙关紧闭，并表明口腔手术后的炎症反应。
方法：进行基因测序以鉴定 CYP450 多态性和评估的手术参数：术前和术后肿胀、牙关紧闭和体温；视觉模拟量表（VAS）自评术后疼痛；使用的解救药物；以及不良反应的严重程度。
结果：使用具有自变量[单核苷酸多态性（SNP）、体重指数（BMI）、手术持续时间和难度]和因变量[术后疼痛总和疼痛强度差值（SPID）、牙关紧闭和肿胀]的多元线性回归模型进行分析。手术持续时间是术后 8 小时和 96 小时疼痛的预测因子，BMI 是术后第 2 天肿胀和牙关紧闭的预测因子。在评估 CYP2C8 和 C9 基因型 SNP 时，与 0 小时相比，正常代谢者在术后各期的疼痛水平均高于中间/差代谢者。在另一项分析中，CYP2C8 和 C9 的差代谢者在术后 8 小时后疼痛程度较低，并且比正常代谢者更早使用解救药物。
结论：布洛芬 600mg 在下颌第三磨牙手术后非常有效地控制炎症性疼痛，没有相关的不良反应；尽管非常轻微，但代谢不良的患者在最初几小时内疼痛水平更高，8 小时后不再如此，并且更早使用止痛药物。
试验注册：该研究于 2017 年 3 月 16 日在 ClinicalTrials.gov 登记（NCT03169127）。
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