Effects of intravenous administration of pirfenidone on horses with experimentally induced endotoxemia.
Abstract: To characterize effects of IV administration of pirfenidone on clinical, biochemical, and hematologic variables and circulating tumor necrosis factor (TNF)-alpha concentrations in horses after infusion of a low dose of endotoxin. Methods: 18 healthy adult horses. Methods: Horses were randomly assigned to 3 groups (n = 6 horses/group) and administered an IV infusion of 30 ng of endotoxin/kg or saline (0.9% NaCl) solution during a 30-minute period. Lipopolysaccharide-pirfenidone horses received endotoxin followed by pirfenidone (loading dose of 11.6 mg/kg and then constant rate infusion [CRI] at 9.9 mg/kg/h for 3 hours). Lipopolysaccharide-saline horses received endotoxin followed by infusion (loading dose and CRI for 3 hours) of saline solution. Saline-pirfenidone horses received saline solution followed by pirfenidone (loading dose and then CRI for 3 hours). Physical examination variables were recorded and blood samples collected at predetermined intervals throughout the 24-hour study period. Blood samples were used for CBCs, biochemical analyses, and determinations of TNF-alpha concentrations. Results: IV infusion of pirfenidone after administration of a low dose of endotoxin failed to attenuate the clinical, clinicopathologic, or cytokine alterations that developed secondary to endotoxin exposure. Intravenous infusion of pirfenidone after administration of saline solution induced mild transient clinical signs, but associated clinicopathologic changes were not detected. Conclusions: IV administration of pirfenidone was tolerated with only mild transient clinical adverse effects during infusion. However, administration of pirfenidone did not protect horses from the systemic effects of experimentally induced endotoxemia. Further studies of related, but more potent, drugs may be warranted.
Publication Date: 2009-08-04 PubMed ID: 19645586DOI: 10.2460/ajvr.70.8.1031Google Scholar: Lookup
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- Clinical Trial
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article concerns the study of how the intravenous administration of a drug called pirfenidone affects horses that have been experimentally induced with endotoxemia. However, the results showed that the drug had no protective effects against the systemic effects of the condition.
Experimental Design
- The study involved 18 healthy adult horses that were randomly divided into three groups, with each group containing six horses.
- A mixture of either a low dose of endotoxin or saline solution was intravenously administered to the horses over a period of 30 minutes. The mixture given to the ‘Lipopolysaccharide-pirfenidone’ group consisted of endotoxin followed by pirfenidone, while the ‘Lipopolysaccharide-saline’ group received endotoxin followed by saline solution. The final group, ‘Saline-pirfenidone’, was treated with saline solution followed by pirfenidone.
- Physical examinations results and blood samples were collected at different intervals throughout a 24-hour study period. The blood samples were used to conduct complete blood count (CBC), biochemical analyses, and measurements of tumor necrosis factor-alpha (TNF-alpha) concentrations.
Results and Conclusion
- Administration of pirfenidone after a low dose of endotoxin did not lower the clinical, clinicopathologic, or cytokine alterations that developed as a result of endotoxin exposure.
- When pirfenidone was infused after saline solution, it caused only mild and temporary clinical signs, but did not bring about any associated clinicopathologic changes.
- The research found that pirfenidone was tolerated and only caused mild temporary clinical adverse effects during infusion. However, it did not provide any protection to horses from the systemic effects of experimentally induced endotoxemia.
- The researchers conclude that further studies may be needed to investigate related, but more potent, drugs.
Cite This Article
APA
Poulin Braim AE, MacDonald MH, Bruss ML, Grattendick KJ, Giri SN, Margolin SB.
(2009).
Effects of intravenous administration of pirfenidone on horses with experimentally induced endotoxemia.
Am J Vet Res, 70(8), 1031-1042.
https://doi.org/10.2460/ajvr.70.8.1031 Publication
Researcher Affiliations
- Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
MeSH Terms
- Analysis of Variance
- Animals
- Endotoxemia / drug therapy
- Endotoxemia / veterinary
- Horse Diseases / drug therapy
- Horses
- Injections, Intravenous / veterinary
- Lipopolysaccharides
- Male
- Pyridones / administration & dosage
- Pyridones / therapeutic use
- Tumor Necrosis Factor-alpha / blood
Citations
This article has been cited 4 times.- Seifirad S, Alquran L. Commentary: Antifibrotics in COVID-19 Lung Disease: Let Us Stay Focused.. Front Med (Lausanne) 2020;7:625440.
- Scavone D, Sgorbini M, Borges AS, Oliveira-Filho JP, Vitale V, Paltrinieri S. Serial measurements of Paraoxonase-1 (PON-1) activity in horses with experimentally induced endotoxemia.. BMC Vet Res 2020 Nov 4;16(1):422.
- Bauquier J, Tudor E, Bailey S. Effect of the p38 MAPK inhibitor doramapimod on the systemic inflammatory response to intravenous lipopolysaccharide in horses.. J Vet Intern Med 2020 Sep;34(5):2109-2116.
- Seifirad S. Pirfenidone: A novel hypothetical treatment for COVID-19.. Med Hypotheses 2020 Nov;144:110005.
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