EVALUATION OF ANTINOCICEPTIVE EFFECT OF THE KETOROLAC-TOPIRAMATE COMBINATION IN THE RAT FORMALIN TEST | ||||
| Bulletin of Pharmaceutical Sciences Assiut University | ||||
| Article 24, Volume 44, Issue 1, June 2021, Page 253-263 PDF (593.15 K) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/bfsa.2021.174151 | ||||
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| Authors | ||||
Claudia Cervantes-Durán 1; Erandi Sánchez-Serrano2; Marcia Yvette Gauthereau-Torres 2; Luis Fernando Ortega-Varela 3
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| 1Bachelor of Information Technology in Sciences, National School of Higher Studies, Morelia Unit, National Autonomous University of Mexico, Morelia, Michoacan | ||||
| 2Division of Graduate Studies, Faculty of Medical and Biological Sciences “Dr. Ignacio Chávez”, Michoacan University of San Nicolás de Hidalgo, Morelia, Michoacan | ||||
| 3Faculty of Public Health and Nursing, Michoacan University of San Nicolás de Hidalgo, Morelia, Michoacan | ||||
| Abstract | ||||
| 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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