Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, P. O. Box 146, 11221 Belgrade, Serbia.
Pharmacol Biochem Behav. 2011 Jan;97(3):611-8. doi: 10.1016/j.pbb.2010.11.007. Epub 2010 Nov 17.
Oxcarbazepine, ibuprofen and etodolac have efficacy in inflammatory pain. The combination of different drugs activates both central and peripheral pain inhibitory pathways to induce additive or synergistic antinociception, and this interaction may allow lower doses of each drug combined and improve the safety profile, with lower side-effects. This study aimed to examine the effects of oxcarbazepine-ibuprofen and oxcarbazepine-etodolac combinations, in a rat model of inflammatory hyperalgesia, and determine the type of interaction between drugs. Rats were intraplantarly injected with carrageenan (0.1 ml, 1%) and the hyperalgesia was assessed by modified paw pressure test. The anti-hyperalgesic effects of oxcarbazepine, ibuprofen and etodolac and oxcarbazepine-ibuprofen and oxcarbazepine-etodolac combinations were examined. Drugs were co-administered in a fixed-dose fractions of the ED₅₀ and the type of interaction was determined by isobolographic analysis. Oxcarbazepine (40-160 mg/kg; p.o.), ibuprofen (10-120 mg/kg; p.o.) and etodolac (5-20 mg/kg; p.o.) produced a significant, dose-dependent anti-hyperalgesia in carrageenan-injected rats. ED₅₀ values (mean±SEM) for oxcarbazepine, ibuprofen and etodolac were 88.17±3.65, 47.07±10.27 and 13.05±1.42 mg/kg, respectively. Oxcarbazepine-ibuprofen and oxcarbazepine-etodolac combinations induced significant and dose-dependent anti-hyperalgesia. Isobolographic analysis revealed that oxcarbazepine exerts a synergistic interaction with ibuprofen, with almost 4-fold reduction of doses of both drugs in combination. In contrast, there was an additive interaction with etodolac. Synergistic interaction of oxcarbazepine with ibuprofen and its additive interaction with etodolac provide new information about the combination pain treatment and could be explored further in patients with inflammatory pain. Adverse effect analysis of the combinations is necessary to verify possible clinical use of the mixtures.
奥卡西平、布洛芬和依托考昔在炎性疼痛中具有疗效。不同药物的联合使用激活了中枢和外周疼痛抑制途径，从而诱导相加或协同的镇痛作用，这种相互作用可能允许联合使用较低剂量的每种药物，并改善安全性，降低副作用。本研究旨在检查奥卡西平-布洛芬和奥卡西平-依托考昔组合在炎性痛觉过敏大鼠模型中的作用，并确定药物之间的相互作用类型。向大鼠足底注射角叉菜胶（0.1ml，1%），通过改良足底压力测试评估痛觉过敏。检查了奥卡西平、布洛芬和依托考昔以及奥卡西平-布洛芬和奥卡西平-依托考昔组合的抗痛觉过敏作用。以 ED₅₀的固定剂量分数共同给予药物，并通过等对数分析确定相互作用的类型。奥卡西平（40-160mg/kg；po）、布洛芬（10-120mg/kg；po）和依托考昔（5-20mg/kg；po）在角叉菜胶注射大鼠中产生了显著的、剂量依赖性的抗痛觉过敏作用。奥卡西平、布洛芬和依托考昔的 ED₅₀值（平均值±SEM）分别为 88.17±3.65、47.07±10.27 和 13.05±1.42mg/kg。奥卡西平-布洛芬和奥卡西平-依托考昔组合诱导了显著的、剂量依赖性的抗痛觉过敏。等对数分析显示，奥卡西平与布洛芬具有协同相互作用，联合使用时两种药物的剂量减少近 4 倍。相比之下，与依托考昔存在相加相互作用。奥卡西平与布洛芬的协同相互作用及其与依托考昔的相加相互作用为联合治疗疼痛提供了新的信息，并且可能在炎性疼痛患者中进一步探索。需要对组合的不良反应进行分析，以验证混合物的可能临床应用。
