Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Colonia Casco de Santo Tomás, Miguel Hidalgo, Ciudad de México 11340, Mexico.
Facultad de Estudios Superiores Zaragoza, UNAM, Av. Guelatao No. 66, Colonia Ejército de Oriente, Iztapalapa, Ciudad de México 09230, Mexico.
Molecules. 2020 Nov 3;25(21):5106. doi: 10.3390/molecules25215106.
Although nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the main types of drugs used to treat pain, they have several adverse effects, and such effects can be reduced by combining two analgesic drugs. The aim of this study was to evaluate the nociceptive activity of methyleugenol combined with either diclofenac or ketorolac, and determine certain parameters of pharmacokinetics. For the isobolographic analysis, the experimental effective dose 30 (ED) was calculated for the drugs applied individually. With these effective doses, the peak plasma concentration (C) was found and the other parameters of pharmacokinetics were established. Methyleugenol plus diclofenac and methyleugenol plus ketorolac decreased licking behavior in a dose-dependent manner in phase II, with an efficacy of 32.9 ± 9.3 and 39.8 ± 9.6%, respectively. According to the isobolographic analysis, the experimental and theoretical ED values were similar for methyleugenol plus diclofenac, suggesting an additive effect, but significantly different for methyleugenol plus ketorolac (3.6 ± 0.5 vs. 7.7 ± 0.6 mg/kg, respectively), indicating a probable synergistic interaction. Regarding pharmacokinetics, the only parameter showing a significant difference was C for the methyleugenol plus diclofenac combination. Even with this difference, the combinations studied may be advantageous for treating inflammatory pain, especially for the combination methyleugenol plus ketorolac.
尽管非甾体抗炎药 (NSAIDs) 是治疗疼痛的主要药物类型之一，但它们有几种不良反应，通过将两种镇痛药结合使用可以减少这种不良反应。本研究的目的是评估甲基丁香酚与双氯芬酸或酮咯酸联合使用的镇痛活性，并确定某些药代动力学参数。对于等辐射分析，计算了单独应用这些药物的实验有效剂量 30 (ED)。用这些有效剂量，发现了最大血浆浓度 (C)，并建立了其他药代动力学参数。甲基丁香酚加双氯芬酸和甲基丁香酚加酮咯酸在第二阶段以剂量依赖的方式降低舔舐行为，效力分别为 32.9 ± 9.3%和 39.8 ± 9.6%。根据等辐射分析，甲基丁香酚加双氯芬酸的实验和理论 ED 值相似，表明存在相加作用，但甲基丁香酚加酮咯酸的 ED 值明显不同（3.6 ± 0.5 与 7.7 ± 0.6 mg/kg），表明可能存在协同作用。关于药代动力学，唯一显示显著差异的参数是甲基丁香酚加双氯芬酸组合的 C。即使存在这种差异，研究中的组合可能有利于治疗炎症性疼痛，特别是甲基丁香酚加酮咯酸的组合。
