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[9004633.] رقم البحث : 9004633 - |
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EVALUATION OF ANTINOCICEPTIVE EFFECT OF THE KETOROLAC-TOPIRAMATE COMBINATION IN THE RAT FORMALIN TEST / تقييم التأثير المضاد للالتهاب لمزيج كيتورولاك - توببيراميت في اختبار الفورمالين بالجرذان |
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قطاع الدراسات الصيدلية / General |
| تخصص البحث : General |
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Bulletin of Pharmaceutical sciences / |
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سارة يوسف محمد ( Sarahyousef30@yahoo.com - ) |
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د/ لويس فرناندو - مؤلف رئيسي |
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علم الأدوية والسموم |
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Combination therapy approaches to manage acute and chronic pain are commonly used. To characterize the interaction between ketorolac and topiramate in the formalin test, female Wistar rats (200-300 g) were submitted to 1% formalin test. Antinociceptive effect was determined by the administration of ketorolac (3, 10, 30 and 100 mg/kg), topiramate (25, 50, 100 and 200 mg/kg) and their combination by oral route; or ketorolac (25, 50, 100 and 200 µg/paw), topiramate (10, 30, 100 and 300 µg/paw) and their combination by local peripheral route. Isobolographic analysis was used in a fixed dose combination (0.5:0.5) to analyze the nature of the interaction of the combination based on the ED50 of ketorolac (62.8±21.9 mg/kg) and topiramate (24.3±8.5 mg/kg) by oral administration; or the ED30 of ketorolac (67.0±7.97 µg/paw) and topiramate (391.3±51.7 µg/paw) by local peripheral route. Combination of these two drugs significantly reduced the number of flinches in second phase of the test. Theoretical ED50 of the oral combination (ED50T) was 43.5±11.7 mg/kg. Experimentally, the ED50 of the combination (ED50E) had a significantly lower value: 16.7±4.0 mg/kg; indicating the presence of supra additive effects (interaction index was 0.38). For local peripheral route, ED30T was 229.21±64.99 µg/kg. Experimentally, the ED30E had a significantly lower value: 62.00±15.72 µg/paw; indicating synergistic effects (interaction index was 0.27). Results show that oral and local peripheral administration of the combination can interact synergistically to reduce inflammatory pain in the rat formalin test. |
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