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Comparative Study of the Efficacy of Flunixin, Ketoprofen and Phenylbutazone in Delman Horses with Mild Colic

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Comparative Study of the Efficacy of Flunixin, Ketoprofen and Phenylbutazone in Delman Horses with Mild Colic Sys Rev Pharm 2020; 11(5): 464 468 A multifaceted review journal in the field of pharmacy E-ISSN 0976-2779 P-ISSN 0975-8453 Comparative Study of the Efficacy of Flunixin, Ketoprofen and Phenylbutazone in Delman Horses with Mild Colic Agus Purnomo1, Arya Pradana Wicaksono2, Dodit Hendrawan2, Muhammad Thohawi Elziyad Purnama3* 1Department of Veterinary Surgery and Radiology, Faculty of Veterinary Medicine, Universitas Gadjah Mada, DI Yogyakarta, 55281, Indonesia 2Postgraduate Studies, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, 60115, Indonesia 3Department of Veterinary Anatomy, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, 60115, Indonesia *Corresponding author E-mail: [email protected] Article History: Submitted: 26.02.2020 Revised: 16.04.2020 Accepted: 21.05.2020 ABSTRACT This study aimed to evaluate the efficacy of flunixin, ketoprofen and multiple range test. The results showed a significant alleviation in all phenylbutazone on serum biochemistry, plasma catecholamines and observed variables on Day 13, although the use of various NSAIDs serum cortisol in Delman horses with mild colic. During the study showed no significant difference. period, 32 horses were evaluated due to mild colic. Flunixin, Keywords: serum biochemical, catecholamine, cortisol, colic, NSAIDs ketoprofen, and phenylbutazone were administered intravenously at Correspondence: the recommended dose rates of 1.0; 2.2 and 4.4 mg/kg, respectively. Muhammad Thohawi Elziyad Purnama Administration of the NSAIDs commenced on Day 1 and continued Department of Veterinary Anatomy, Faculty of Veterinary Medicine, every 12 h for 12 days. Blood samples collected between days 2, 5, 9 Universitas Airlangga, Surabaya, 60115, Indonesia and 13 to evaluate AST, ALP, GGT, creatinine, urea, epinephrine, E-mail: [email protected] norepinephrine, and cortisol level. The data analysis performed using DOI: 10.31838/srp.2020.5.64 Multivariate analysis of variance (Manova) followed by Duncan @Advanced Scientific Research. All rights reserved INTRODUCTION MATERIALS AND METHODS Adult horse deaths by 50% were caused by digestive diseases, Ethical approval such as colic, diarrhea, or enterotoxemia. The incidence of This study approved by Indonesian Horse Veterinarian colic is estimated at 13.6% per year in horses aged 6 months Association and according to the standard operating or more in 28 US states.1 Although 75% of colic cases recover procedure for colic treatment. in less than 24 hours, 67% of horses with colic were examined by veterinarians, of which 85% receive intensive treatment. Animals The probability of a horses' death rate is very high when All Delman horses with mild colic examined at each referred to an animal clinic.2 enclosured between June 29 to August 21, 2019, were eligible Colic is a general term used for symptoms of abdominal pain for inclusion in this study. To be included in the study, a that can be caused by a variety of different conditions. Colic blood sample for the measurement of selected variables had is a symptom that must be anticipated by horse owners to have been collected from the affected horse within 30 because it can cause horse death. In some cases, colic can minutes. For eligible horses (age, sex, breed, heart rate at cause death within hours.3 Other studies have reported the initial evaluation, and suspected mild colic) enrolled to colic associated with food material, parasites infections, evaluate the blood sample. dental diseases, access to water, but the cause of the majority 4 of colic cases is unknown. Administration of the NSAIDs Flunixin, ketoprofen, and phenylbutazone belong to a group Administration of the NSAIDs commenced at 07.00 hours on of nonsteroidal anti-inflammatory drugs (NSAIDs) Day 1, and continued every 12 h for 12 days. Flunixin compounds. Other compounds such as salicylates (aspirin), meglumine (Flumine, Jaapharm Canada Inc); ketoprofen propionic acid (ibuprofen, phenoprofen, ketoprofen and (Ketofen, Zoetis) and phenylbutazone (Phenylbute, Phoenix naproxen), pyrazolone (phenylbutazone), anthranilic acid Pharm) were administered intravenously via an indwelling (meclofenamic acid), and aminonicotinic acid (flunixin) are 6.5 mm catheter (Equivet Stallion, North Yorkshire, UK) in also included as NSAIDs derivatives. The use of NSAIDs is as the jugular vein, at the recommended dose rates of 1.0; 2.2 an anti-pyretic, anti-inflammatory, and analgesic and 4.4 mg/kg, respectively. 5 compound. The efficacy of NSAIDs is still the first choice for reducing Serum evaluation 6 colic symptoms. This study aimed to evaluate the efficacy of Each blood sample for serum measurement was allowed to flunixin, ketoprofen and phenylbutazone on serum clot before centrifugation (1500 X g for 10 minutes), and an biochemistry, plasma catecholamines and serum cortisol in aliquot of the serum was stored at -80oC until analyzed using Delman horses with mild colic. the clinical chemistry analyzer Hitachi 902® (Roche Diagnostics, USA) for serum biochemical level7 and validated using radioimmunoassay for serum cortisol.8 Each blood sample for measurement of plasma epinephrine and norepinephrine concentrations was centrifuged immediately after collection, and plasma aliquots were stored at -80oC until analyzed using highly-performance liquid 464 Systematic Review Pharmacy Vol 11, Issue 5, 2020 Muhammad Thohawi Elziyad Purnama et al / Comparative Study of the Efficacy of Flunixin, Ketoprofen and Phenylbutazone in Delman Horses with Mild Colic chromatography (HPLC).9 All blood samples collected GGT (Figure 1-3). Oxyphenbutazone inhibits between days 2, 5, 9 and 13 to determine the trend after phenylbutazone metabolism. The liver's capacity to NSAIDs administration. metabolize phenylbutazone is not optimal at relatively low doses of the drug, producing dose-dependent kinetics.16 Statistical analysis Phenylbutazone is widely used in horses for various All data on the following variables i.e. aspartate musculoskeletal disorders. Phenylbutazone also has an aminotransferase (AST), alkaline phosphatase (ALP), endotoxin antagonistic effect on intestinal motility. gamma‐glutamyltransferase (GGT), creatinine, urea, Phenylbutazone inhibits prostaglandin synthesis at low epinephrine, norepinephrine, and cortisol level compared plasma concentrations in horses (5- 6 This between days 2, 5, 9 and 13 after administered NSAIDs, difference may be due to species differences in the structure respectively. The data analysis performed using Multivariate of Cox.17 An initial dose of 4.4 mg/kg every 12 hours on the analysis of variance (Manova) followed by Duncan multiple first day of therapy is followed by a decrease in dose and an range test (p<0.05) (IBM, USA). increase in the dosing interval for subsequent therapy.18 Due to the accumulated withdrawal time of long-standing RESULTS AND DISCUSSIONS phenylbutazone and oxyphenbutazone, chronic therapy During the study period, 32 horses were evaluated due to must be at the lowest possible dose and the longest dose 19 mild colic. NSAIDs administered in horses with colic i.e. interval that may still control pain. flunixin (n=11), ketoprofen (n=11), and phenylbutazone Decreased creatinine (Figure 4) and urea (Figure 5) levels (n=10). There were no significant differences (p>0.05) after Cox-1 and Cox-2 inhibition occur in peripheral 20,21 between the administration of flunixin, ketoprofen, and tissues. This inhibition interferes with the process of phenylbutazone on the following variables: AST (Figure 1), converting arachidonic acid into prostaglandins. ALP (Figure 2), GGT (Figure 3), creatinine (Figure 4), urea Prostaglandins are the main protective component in the (Figure 5), epinephrine (Figure 6), norepinephrine (Figure hemodynamic function of the kidneys. 63% of NSAIDs are 7), and cortisol level (Figure 8). metabolized through glucuronidation and 34% through On the other hand, the results showed significantly different sulfation in the liver. Water-soluble metabolites will be (p<0.05) between days 2, 5, 9 and 13 (Figure 1-8). Compared excreted through the kidneys. N-Acetyl p-benzoquinone to the first day when the initial diagnosis of mild colic in (NAPQI) is a reactive intermediate formed when oxidation horses followed by a pre-treatment blood collection, all <5% paracetamol by the cytochrome P-450 enzyme. The variables showed an alleviation trend in levels. The alleviation decrease in urea in the results of this study was obtained of serum biochemical, plasma catecholamine and serum because the effect of NSAIDs was converted to inactive cortisol levels were highly significant on Day 13. metabolites, non-electrophilic, and decreased toxic effects for Non-steroidal anti-inflammatory drugs (NSAIDs) are the liver and kidneys. The decrease in NAPQI will prevent important veterinary medicines for most mammalian tubular damage which can be characterized by a decrease in 22 species. In recent years, the use of NSAIDs has increased serum creatinine and urea levels. rapidly to handle clinical cases.10 NSAIDs can reduce pain and inflammation without immunosuppressive and CONCLUSION metabolic side effects associated with corticosteroids (Figure It can be concluded that there were no significant on the 8). Flunixin meglumine is used in veterinary practice as an following variable: AST, ALP, GGT, creatinine, urea, analgesic, antipyretic, and anti-inflammatory drug. The use epinephrine, norepinephrine, and cortisol after administered of flunixin in ruminants for the treatment of various flunixin,
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