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174151

EVALUATION OF ANTINOCICEPTIVE EFFECT OF THE KETOROLAC-TOPIRAMATE COMBINATION IN THE RAT FORMALIN TEST

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Last updated: 04 Jan 2025

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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.

DOI

10.21608/bfsa.2021.174151

Authors

First Name

Claudia

Last Name

Cervantes-Durán

MiddleName

-

Affiliation

Bachelor of Information Technology in Sciences, National School of Higher Studies, Morelia Unit, National Autonomous University of Mexico, Morelia, Michoacan

Email

espparmex@hotmail.com

City

-

Orcid

0000-0002-6124-9139

First Name

Erandi

Last Name

Sánchez-Serrano

MiddleName

-

Affiliation

Division of Graduate Studies, Faculty of Medical and Biological Sciences “Dr. Ignacio Chávez", Michoacan University of San Nicolás de Hidalgo, Morelia, Michoacan

Email

-

City

-

Orcid

-

First Name

Marcia

Last Name

Gauthereau-Torres

MiddleName

Yvette

Affiliation

Division of Graduate Studies, Faculty of Medical and Biological Sciences “Dr. Ignacio Chávez", Michoacan University of San Nicolás de Hidalgo, Morelia, Michoacan

Email

mgtorres@umich.mx

City

-

Orcid

0000-0002-2431-0471

First Name

Luis

Last Name

Ortega-Varela

MiddleName

Fernando

Affiliation

Faculty of Public Health and Nursing, Michoacan University of San Nicolás de Hidalgo, Morelia, Michoacan

Email

lfortega@umich.mx

City

-

Orcid

0000-0003-1830-7468

Volume

44

Article Issue

1

Related Issue

25283

Issue Date

2021-06-01

Receive Date

2020-09-28

Publish Date

2021-06-01

Page Start

253

Page End

263

Print ISSN

1110-0052

Online ISSN

3009-7703

Article File

BFSA_Volume 44_Issue 1_Pages 253-263.pdf

PDF . 607.4kB

Link

https://bpsa.journals.ekb.eg/article_174151.html

Detail API

https://bpsa.journals.ekb.eg/service?article_code=174151

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24

Type

Original Article

Type Code

1,096

Publication Type

Journal

Publication Title

Bulletin of Pharmaceutical Sciences Assiut University

Publication Link

https://bpsa.journals.ekb.eg/

MainTitle

EVALUATION OF ANTINOCICEPTIVE EFFECT OF THE KETOROLAC-TOPIRAMATE COMBINATION IN THE RAT FORMALIN TEST

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Article

Created At

22 Jan 2023