Research Article
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Koyunlarda tolfenamik asitin farklı dozlarda uygulamasının hematolojik ve biyokimyasal parametrelere etkisi

Year 2023, Volume: 5 Issue: 2, 44 - 48, 31.12.2023
https://doi.org/10.51755/turkvetj.1398646

Abstract

Bu araştırmanın amacı koyunlara tolfenamik asitin 2, 4, 8 ve 16 mg/kg dozda damar içi yolla uygulaması sonrası hematolojik ve biyokimyasal parametrelerdeki değişimi belirlemektir. Araştırma 8 adet sağlıklı Akkaraman ırkı koyun üzerinde gerçekleştirildi. Koyunlara 2, 4, 8 ve 16 mg/kg dozda tolfenamik asit damar içi yolla uygulandı. Kan örnekleri ilaç uygulaması öncesi (0.saat, kontrol) ve uygulamayı takiben 72. saatte alındı. Hematolojik parametrelerin analizi kan hücresi sayım cihazında ve biyokimyasal parametrelerin analizi otoanalizör cihazında gerçekleştirildi. Koyunlara tolfenamik asitin 2, 4 ve 8 mg/kg dozda uygulaması hematolojik (akyuvar, alyuvar, hemoglobin, hematokrit ve trombosit) ve biyokimyasal parametrelerde (albumin, alkalen fosfataz, alanin aminotransferaz, aspartat aminotransferaz, gama glutamil transferaz, kolesterol, total bilirubin, trigliserit, kreatinin ve üre) herhangi bir değişikliğe neden olmadığı belirlendi (p>0.05). Tolfenamik asitin 16 mg/kg dozda uygulaması kreatinin ve üre değerlerinde önemli artışa neden olurken (p<0.05) diğer parametrelerde herhangi bir farklılık görülmedi (p>0.05). Sonuç olarak tolfenamik asitin koyunlara 2, 4 ve 8 mg/kg dozlarında uygulanması iyi tolere edilirken, 16 mg/kg dozunun böbrek fonksiyonları üzerinde istenmeyen etkilere neden olduğu belirlendi. Ancak koyunlarda tolfenamik asitin güvenilirliğinin histopatolojik ve moleküler olarak ortaya konulmasına ihtiyaç vardır.

Ethical Statement

Deneysel prosedür için Selçuk Üniversitesi, Veteriner Fakültesi, Etik Kurulu Başkanlığı’ndan Etik onay alındı (2015/44).

Supporting Institution

Türkiye Bilimsel ve Teknolojik Araştırma Kurumu

Thanks

Bu proje Türkiye Bilimsel ve Teknolojik Araştırma Kurumu (Proje No, 215O702) tarafından finanse edilmiştir.

References

  • Ahmed, S., Sheraz, M. A., & Ahmad, I. (2018). Tolfenamic acid. Profiles of Drug Substances, Excipients and Related Methodology, 43, 255–319.doi:10.1016/bs.podrm.2018.01.001.
  • Anonim (2023). https://www.agrovetmarket.com/Files/187c26f8-7427-402b-8ee1-20fba394e5b8.pdf).
  • Cetin, G., Corum, O., Corum, D. D., Atik, O., Altan, F., Turk, E., Tekeli, I. O., Eser Fakı, H., & Uney, K. (2022).Pharmacokinetics of intravenous meloxicam, ketoprofen and tolfenamic acid in chukar partridge (Alectoris chukar). British Poultry Science, 63(1), 14–20. doi: 10.1080/00071668.2021.1990211.
  • Cetin, G., Durna Corum, D., Corum, O., Atik, O., Coskun, D., & Uney, K. (2021). Effect of ketoprofen and tolfenamic acid on intravenous pharmacokinetics of ceftriaxone in sheep. Journal of Veterinary Pharmacology and Therapeutics, 44(6), 945–951. doi: 10.1111/jvp.13001.
  • Cordeiro, A. R. R. D. A., Bezerra, T. K. A., & Madruga, M. S. (2022). Valuation of goat and sheep by-products: Challenges and opportunities for their use. Animals, 12(23), 3277. doi: 10.3390/ani12233277.
  • Corum, O., Atik, O., Corum, D. D., Er, A., & Uney, K. (2019). Pharmacokinetics of tolfenamic acid in red-eared slider turtles (Trachemys scripta elegans). Veterinary Anaesthesia and Analgesia, 46(5), 699–706. doi: 10.1016/j.vaa.2019.05.009.
  • Corum, O., Corum, D. D., Er, A., Yıldız, R., & Uney, K., (2018). Pharmacokinetics and bioavailability of tolfenamic acid in sheep. Journal of Veterinary Pharmacology and Therapeutics, 41(6), 871–877. doi: 10.1111/jvp.12702.
  • Çorum et al. / Effect Of Different Doses Of Tolfenamic Acid On Hematological And Biochemical Parameters İn Sheep, 5(2): 44-48, 2023
  • Coskun, D., Corum, O., Durna Corum, D., Cetin, G., Irmak, M., Ceyhan, H. R., & Uney, K. (2023). Age‐related changes in the pharmacokinetics of meloxicam after intravenous administration in sheep. Journal of Veterinary Pharmacology and Therapeutics, 46(5), 326–331. doi: 10.1111/jvp.13404.
  • CVMP (2023 November 08). Committee for Veterinary Medicinal Products. Tolfenamic acid, Summary Report. https://www.ema.europa.eu/en/documents/mrl-report/tolfenamic-acid-summary-report-committee-veterinary-medicinal-products_en.pdf.
  • Çetin, G., & Türk, E. (2020). Keçilerde tolfenamik asitin artan dozlarda uygulanmasının biyokimyasal parametrelere etkisi. Dicle Üniversitesi Veteriner Fakültesi Dergisi, 13(2), 162–165. doi: 10.47027/duvetfd.824424.
  • Harirforoosh, S., & Jamali, F. (2009). Renal adverse effects of nonsteroidal anti-inflammatory drugs. Expert Opinion on Drug Safety, 8, 669–681. doi: 10.1517/14740330903311023.
  • Kaya S. (2006). Aspirin ve Benzeri ilaçlar. In S. Kaya (Eds.), Veteriner Farmakoloji, Medisan Yayın evi, Ankara.
  • Landoni, M. F., Cunningham, F. M., & Lees, P. (1996). Pharmacokinetics and pharmacodynamics of tolfenamic acid in calves. Research in Veterinary Science, 61(1), 26–32.doi: 10.1016/s0034-5288(96)90106-x.
  • Lees, P. (2009). Analgesic, antiinflammatory, Antipyretic Drugs. In J. E. Riviere & M. G. Papich. Veterinary Pharmacology and Therapeutics (pp.457). Ninth edition, Wiley-Blackwell.
  • Lees, P., McKellar, Q. A., Foot, R., & Gettinby, G. (1998). Pharmacodynamics and pharmacokinetics of tolfenamic acid in ruminating calves: evaluation in models of acute inflammation. Veterinary Journal, 155(3), 275–288. doi: 10.1016/s1090-0233(05)80024-3.
  • Lizarraga, I., & Chambers, J. P. (2012). Use of analgesic drugs for pain management in sheep. New Zealand Veterinary Journal, 60(2), 87–94. doi: 10.1080/00480169.2011.642772.
  • McKellar, Q. A., Lees, P., & Gettinby, G. (1994). Pharmacodynamics of tolfenamic acid in dogs. Evaluation of dose response relationships. European Journal of Pharmacology, 253(3), 191–200. doi: 10.1016/0014-2999(94)90191-0.
  • Moilanen, E., & Kankaanranta, H. (1994). Tolfenamic acid and leukotriene synthesis inhibition. Pharmacology Toxicology, 75, 60–63. doi: 10.1111/j.1600-0773.1994.tb02000.x.
  • Palviainen, M. J., Junnikkala, S., Raekallio, M., Meri, S., & Vainio, O. (2015). Activation of complement system in kidney after ketoprofen-induced kidney injury in sheep. Acta Veterinaria Scandinavica, 57, 15. doi: 10.1186/s13028-015-0106-2.
  • Patel, S. D., Sadariya, K. A., Gothi, A. K., Patel, U. D., Jain, M. R., Bhavsar, S. K., & Thaker, A. M. (2011). Safety of tolfenamic acid following repeated intramuscular administration in wistar rats. Pharma Science Monitor an International Journal of Pharmaceutical Sciences, 2(2), 79–85.
  • Sidhu, P. K., Landoni, M. F., & Lees, P. (2005). Influence of Marbofloxacin on the pharmacokinetics and pharmacodynamics of tolfenamic acid in calves. Journal of Veterinary Pharmacology and Therapeutics, 28(1), 109–119. doi: 10.1111/j.1365-2885.2004.00633.x.
  • Sidhu, P. K., Landoni, M.F., & Lees, P. (2006). Pharmacokinetic and pharmacodynamics interactions of tolfenamic acid and marbofloxacin in goats. Research in Veterinary Science, 80(1), 79–90. doi: 10.1016/j.rvsc.2005.04.008.
  • Tekeli, I. O., Turk, E., Durna Corum, D., Corum, O., Kırgız, F. C., & Uney, K. (2020). Effect of dose on the intravenous pharmacokinetics of tolfenamic acid in goats. Journal of Veterinary Pharmacology and Therapeutics, 43(5), 435–439.doi: 10.1111/jvp.12898.
  • Turk, E., Tekeli, I. O, Durna Corum D, Corum O, Altinok Yipel F, Ilhan A, Emiroglu SB, Uguz H, Uney K. (2021) Pharmacokinetics of tolfenamic acid in goats after different administration routes. J Vet Pharmacol Ther. May;44(3):367-373. doi: 10.1111/jvp.12949.
  • Turk, E., Tekeli, I. O., Corum, O., Durna Corum, D., Kırgız, F. C., Cetin, G., Arslan Atessahin, D., & Uney, K. (2021c). Pharmacokinetics of meloxicam, carprofen, and tolfenamic acid after intramuscular and oral administration in Japanese quails (Coturnix coturnix japonica). Journal of Veterinary Pharmacology and Therapeutics, 44(3), 388–396. doi: 10.1111/jvp.12972.
  • Turk, E., Tekeli, I. O., Durna Corum, D., Corum, O., Sakin, F., & Uney, K. (2021a). Pharmacokinetics of tolfenamic acid after different administration routes in geese (Anser cygnoides). Journal of Veterinary Pharmacology and Therapeutics, 44(3), 381–387. doi: 10.1111/jvp.12956.
  • Weir, M. R. (2002). Renal effects of nonselective non steroidal antiinflammatory drugs and coxibs. Cleveland Clinic Journal of Medicine, 69(1), 53–58.
  • Yıldız, R., Corum, O., Atik, O., Durna Corum, D., Altan, F., Ok, M., & Uney, K. (2019). Changes in novel gastrointestinal and renal injury markers in the blood plasma of sheep following increasing intravenous doses of tolfenamic acid. Acta Veterinaria Hungarica, 67(1), 87–97. doi: 10.1556/004.2019.010.

Effect of different doses of tolfenamic acid on hematological and biochemical parameters in sheep

Year 2023, Volume: 5 Issue: 2, 44 - 48, 31.12.2023
https://doi.org/10.51755/turkvetj.1398646

Abstract

The aim of this study is to determine the change in hematological and biochemical parameters after intravenous administration of tolfenamic acid to sheep at doses of 2, 4, 8 and 16 mg/kg. The research was carried out on 8 healthy Akkaraman breed sheep. Tolfenamic acid was administered intravenously to sheep at doses of 2, 4, 8 and 16 mg/kg. Blood samples were taken before drug administration (0 hour, control) and at 72 hour following the administration. Analysis of hematological parameters was performed on a blood cell counter, and analysis of biochemical parameters was performed on an autoanalyzer. Administration of tolfenamic acid to sheep at doses of 2, 4 and 8 mg/kg did not cause any changes in hematological (white blood cells, red blood cells, hemoglobin, hematocrit and platelets) and biochemical (albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, cholesterol, total bilirubin, triglyceride, creatinine and urea) parameters (p>0.05). While the administration of tolfenamic acid at a dose of 16 mg/kg caused a significant increase in creatinine and urea (p<0.05), no difference was observed in other parameters (p>0.05). As a result, the application of tolfenamic acid to sheep at doses of 2, 4 and 8 mg/kg was well tolerated, while the dose of 16 mg/kg caused undesirable effects on kidney functions. However, there is a need to demonstrate the safety of tolfenamic acid in sheep histopathologically and molecularly.

References

  • Ahmed, S., Sheraz, M. A., & Ahmad, I. (2018). Tolfenamic acid. Profiles of Drug Substances, Excipients and Related Methodology, 43, 255–319.doi:10.1016/bs.podrm.2018.01.001.
  • Anonim (2023). https://www.agrovetmarket.com/Files/187c26f8-7427-402b-8ee1-20fba394e5b8.pdf).
  • Cetin, G., Corum, O., Corum, D. D., Atik, O., Altan, F., Turk, E., Tekeli, I. O., Eser Fakı, H., & Uney, K. (2022).Pharmacokinetics of intravenous meloxicam, ketoprofen and tolfenamic acid in chukar partridge (Alectoris chukar). British Poultry Science, 63(1), 14–20. doi: 10.1080/00071668.2021.1990211.
  • Cetin, G., Durna Corum, D., Corum, O., Atik, O., Coskun, D., & Uney, K. (2021). Effect of ketoprofen and tolfenamic acid on intravenous pharmacokinetics of ceftriaxone in sheep. Journal of Veterinary Pharmacology and Therapeutics, 44(6), 945–951. doi: 10.1111/jvp.13001.
  • Cordeiro, A. R. R. D. A., Bezerra, T. K. A., & Madruga, M. S. (2022). Valuation of goat and sheep by-products: Challenges and opportunities for their use. Animals, 12(23), 3277. doi: 10.3390/ani12233277.
  • Corum, O., Atik, O., Corum, D. D., Er, A., & Uney, K. (2019). Pharmacokinetics of tolfenamic acid in red-eared slider turtles (Trachemys scripta elegans). Veterinary Anaesthesia and Analgesia, 46(5), 699–706. doi: 10.1016/j.vaa.2019.05.009.
  • Corum, O., Corum, D. D., Er, A., Yıldız, R., & Uney, K., (2018). Pharmacokinetics and bioavailability of tolfenamic acid in sheep. Journal of Veterinary Pharmacology and Therapeutics, 41(6), 871–877. doi: 10.1111/jvp.12702.
  • Çorum et al. / Effect Of Different Doses Of Tolfenamic Acid On Hematological And Biochemical Parameters İn Sheep, 5(2): 44-48, 2023
  • Coskun, D., Corum, O., Durna Corum, D., Cetin, G., Irmak, M., Ceyhan, H. R., & Uney, K. (2023). Age‐related changes in the pharmacokinetics of meloxicam after intravenous administration in sheep. Journal of Veterinary Pharmacology and Therapeutics, 46(5), 326–331. doi: 10.1111/jvp.13404.
  • CVMP (2023 November 08). Committee for Veterinary Medicinal Products. Tolfenamic acid, Summary Report. https://www.ema.europa.eu/en/documents/mrl-report/tolfenamic-acid-summary-report-committee-veterinary-medicinal-products_en.pdf.
  • Çetin, G., & Türk, E. (2020). Keçilerde tolfenamik asitin artan dozlarda uygulanmasının biyokimyasal parametrelere etkisi. Dicle Üniversitesi Veteriner Fakültesi Dergisi, 13(2), 162–165. doi: 10.47027/duvetfd.824424.
  • Harirforoosh, S., & Jamali, F. (2009). Renal adverse effects of nonsteroidal anti-inflammatory drugs. Expert Opinion on Drug Safety, 8, 669–681. doi: 10.1517/14740330903311023.
  • Kaya S. (2006). Aspirin ve Benzeri ilaçlar. In S. Kaya (Eds.), Veteriner Farmakoloji, Medisan Yayın evi, Ankara.
  • Landoni, M. F., Cunningham, F. M., & Lees, P. (1996). Pharmacokinetics and pharmacodynamics of tolfenamic acid in calves. Research in Veterinary Science, 61(1), 26–32.doi: 10.1016/s0034-5288(96)90106-x.
  • Lees, P. (2009). Analgesic, antiinflammatory, Antipyretic Drugs. In J. E. Riviere & M. G. Papich. Veterinary Pharmacology and Therapeutics (pp.457). Ninth edition, Wiley-Blackwell.
  • Lees, P., McKellar, Q. A., Foot, R., & Gettinby, G. (1998). Pharmacodynamics and pharmacokinetics of tolfenamic acid in ruminating calves: evaluation in models of acute inflammation. Veterinary Journal, 155(3), 275–288. doi: 10.1016/s1090-0233(05)80024-3.
  • Lizarraga, I., & Chambers, J. P. (2012). Use of analgesic drugs for pain management in sheep. New Zealand Veterinary Journal, 60(2), 87–94. doi: 10.1080/00480169.2011.642772.
  • McKellar, Q. A., Lees, P., & Gettinby, G. (1994). Pharmacodynamics of tolfenamic acid in dogs. Evaluation of dose response relationships. European Journal of Pharmacology, 253(3), 191–200. doi: 10.1016/0014-2999(94)90191-0.
  • Moilanen, E., & Kankaanranta, H. (1994). Tolfenamic acid and leukotriene synthesis inhibition. Pharmacology Toxicology, 75, 60–63. doi: 10.1111/j.1600-0773.1994.tb02000.x.
  • Palviainen, M. J., Junnikkala, S., Raekallio, M., Meri, S., & Vainio, O. (2015). Activation of complement system in kidney after ketoprofen-induced kidney injury in sheep. Acta Veterinaria Scandinavica, 57, 15. doi: 10.1186/s13028-015-0106-2.
  • Patel, S. D., Sadariya, K. A., Gothi, A. K., Patel, U. D., Jain, M. R., Bhavsar, S. K., & Thaker, A. M. (2011). Safety of tolfenamic acid following repeated intramuscular administration in wistar rats. Pharma Science Monitor an International Journal of Pharmaceutical Sciences, 2(2), 79–85.
  • Sidhu, P. K., Landoni, M. F., & Lees, P. (2005). Influence of Marbofloxacin on the pharmacokinetics and pharmacodynamics of tolfenamic acid in calves. Journal of Veterinary Pharmacology and Therapeutics, 28(1), 109–119. doi: 10.1111/j.1365-2885.2004.00633.x.
  • Sidhu, P. K., Landoni, M.F., & Lees, P. (2006). Pharmacokinetic and pharmacodynamics interactions of tolfenamic acid and marbofloxacin in goats. Research in Veterinary Science, 80(1), 79–90. doi: 10.1016/j.rvsc.2005.04.008.
  • Tekeli, I. O., Turk, E., Durna Corum, D., Corum, O., Kırgız, F. C., & Uney, K. (2020). Effect of dose on the intravenous pharmacokinetics of tolfenamic acid in goats. Journal of Veterinary Pharmacology and Therapeutics, 43(5), 435–439.doi: 10.1111/jvp.12898.
  • Turk, E., Tekeli, I. O, Durna Corum D, Corum O, Altinok Yipel F, Ilhan A, Emiroglu SB, Uguz H, Uney K. (2021) Pharmacokinetics of tolfenamic acid in goats after different administration routes. J Vet Pharmacol Ther. May;44(3):367-373. doi: 10.1111/jvp.12949.
  • Turk, E., Tekeli, I. O., Corum, O., Durna Corum, D., Kırgız, F. C., Cetin, G., Arslan Atessahin, D., & Uney, K. (2021c). Pharmacokinetics of meloxicam, carprofen, and tolfenamic acid after intramuscular and oral administration in Japanese quails (Coturnix coturnix japonica). Journal of Veterinary Pharmacology and Therapeutics, 44(3), 388–396. doi: 10.1111/jvp.12972.
  • Turk, E., Tekeli, I. O., Durna Corum, D., Corum, O., Sakin, F., & Uney, K. (2021a). Pharmacokinetics of tolfenamic acid after different administration routes in geese (Anser cygnoides). Journal of Veterinary Pharmacology and Therapeutics, 44(3), 381–387. doi: 10.1111/jvp.12956.
  • Weir, M. R. (2002). Renal effects of nonselective non steroidal antiinflammatory drugs and coxibs. Cleveland Clinic Journal of Medicine, 69(1), 53–58.
  • Yıldız, R., Corum, O., Atik, O., Durna Corum, D., Altan, F., Ok, M., & Uney, K. (2019). Changes in novel gastrointestinal and renal injury markers in the blood plasma of sheep following increasing intravenous doses of tolfenamic acid. Acta Veterinaria Hungarica, 67(1), 87–97. doi: 10.1556/004.2019.010.

Details

Primary Language Turkish
Subjects Veterinary Pharmacology
Journal Section Research Article
Authors

Orhan ÇORUM 0000-0003-3168-2510

Duygu DURNA ÇORUM 0000-0003-1567-991X

Ayşe ER 0000-0002-6900-0055

Kamil ÜNEY 0000-0002-8674-4873

Project Number , 215O702
Early Pub Date December 27, 2023
Publication Date December 31, 2023
Submission Date November 30, 2023
Acceptance Date December 25, 2023
Published in Issue Year 2023Volume: 5 Issue: 2

Cite

APA ÇORUM, O., DURNA ÇORUM, D., ER, A., ÜNEY, K. (2023). Koyunlarda tolfenamik asitin farklı dozlarda uygulamasının hematolojik ve biyokimyasal parametrelere etkisi. Turkish Veterinary Journal, 5(2), 44-48. https://doi.org/10.51755/turkvetj.1398646