Ortiz Mario I, Castañeda-Hernández Gilberto
Area Académica de Medicina del Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Pachuca, Hidalgo 42090, Mexico.
Eur J Pain. 2008 Feb;12(2):233-41. doi: 10.1016/j.ejpain.2007.05.008. Epub 2007 Jul 2.
It has been shown that the association of non-steroidal anti-inflammatory drugs (NSAIDs) with opioid analgesic agents can increase their antinociceptive activity, allowing the use of lower doses and thus limiting side effects. Therefore, the aim of the present study was to examine the possible pharmacological interaction between lumiracoxib and codeine or nalbuphine at the local peripheral level in the rat using the 1% formalin test and isobolographic analysis. Lumiracoxib, codeine, nalbuphine or fixed-dose ratios lumiracoxib-codeine or lumiracoxib-nalbuphine combinations were administrated locally in the formalin-injured paw and the antinociceptive effect was evaluated using the 1% formalin test. All treatments produced a dose-dependent antinociceptive effect. ED(40) values were estimated for the individual drugs and an isobologram was constructed. The derived theoretical ED(40)'s for the lumiracoxib-codeine and lumiracoxib-nalbuphine combinations were 423.4+/-31.3 microg/paw and 310.9+/-24.2 microg/paw, respectively, being significantly higher than the actually observed experimental ED(40) values, 233.2+/-30.9 microg/paw and 132.7+/-11.6 microg/paw, respectively. These results correspond to a synergistic interaction between lumiracoxib and opioids at the local peripheral level, potency being about two times higher with regard to that expected from the addition of the effects of the individual drugs. Data suggest that low doses of the lumiracoxib-opioids combination can interact synergistically at the peripheral level and therefore this drug association may represent a therapeutic advantage for the clinical treatment of inflammatory pain.
研究表明，非甾体抗炎药（NSAIDs）与阿片类镇痛药联合使用可增强其镇痛活性，从而允许使用更低剂量，进而限制副作用。因此，本研究旨在利用1%福尔马林试验和等效应线图分析法，在大鼠局部外周水平研究氯美昔布与可待因或纳布啡之间可能存在的药理相互作用。将氯美昔布、可待因、纳布啡或固定剂量比例的氯美昔布 - 可待因或氯美昔布 - 纳布啡组合局部注射到福尔马林致伤的爪子中，并使用1%福尔马林试验评估镇痛效果。所有处理均产生剂量依赖性镇痛作用。估算了各药物的ED(40)值并构建了等效应线图。氯美昔布 - 可待因和氯美昔布 - 纳布啡组合的理论推导ED(40)分别为423.4±31.3μg/爪和310.9±24.2μg/爪，显著高于实际观察到的实验ED(40)值，分别为233.2±30.9μg/爪和132.7±11.6μg/爪。这些结果表明氯美昔布与阿片类药物在局部外周水平存在协同相互作用，其效力比各药物单独作用效果相加预期的效力高约两倍。数据表明，低剂量的氯美昔布 - 阿片类药物组合在外周水平可产生协同相互作用，因此这种药物联合可能对炎性疼痛的临床治疗具有治疗优势。
