The effects of pentoxifylline infusion on plasma 6-keto-prostaglandin F1 alpha and ex vivo endotoxin-induced tumour necrosis factor activity in horses.
Abstract: Pentoxifylline (7.5 mg/kg) was bolused intravenously to eight healthy horses and was immediately followed by infusion (1.5 mg/kg/h) for 3 h. Clinical parameters were recorded and blood samples were collected for 24 h. Plasma was separated and concentrations of pentoxifylline, its reduced metabolite I, and 6-keto-prostaglandin F1 alpha were determined. Heparinized whole blood was also incubated ex vivo with 1 ng Escherichi coli endotoxin/mL blood for 6 h before determination of plasma tumour necrosis factor activity. The peak plasma concentrations of pentoxifylline and metabolite I occurred at 15 min after bolus injection and were 9.2 +/- 1.4 and 7.8 +/- 4.3 micrograms/mL, respectively. The half-life of elimination (t1/2 beta) of pentoxifylline was 1.44 h and volume of distribution (Vdarea) was 0.94 L/kg. The mean plasma concentration of 6-keto-prostaglandin F1 alpha increased over time, with a significant increase occurring 30 min after the bolus administration. Ex vivo plasma endotoxin-induced tumour necrosis factor activity was significantly decreased at 1.5 and 3 h of infusion. These results indicate that infusion of pentoxifylline will increase 6-keto-prostaglandin F1 alpha and significantly suppress endotoxin-induced tumour necrosis factor activity in horses during the period of infusion.
Publication Date: 1998-02-07 PubMed ID: 9430774DOI: 10.1046/j.1365-2885.1997.00090.xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study investigates the effects of pentoxifylline infusion on plasma concentrations of 6-keto-prostaglandin F1 alpha and how it could suppress endotoxin-induced tumour necrosis factor activity in horses.
Experimental Procedure
- Pentoxifylline, at a dose of 7.5 mg/kg, was intravenously injected into eight healthy horses, followed by an infusion at a rate of 1.5 mg/kg/h over a period of 3 hours.
- The horses’ clinical parameters were monitored and blood samples were collected over a 24-hour period.
- The plasma was then separated from the blood samples and the concentrations of pentoxifylline, its metabolite I, and 6-keto-prostaglandin F1 alpha were measured.
- Additionally, heparinized whole blood was incubated ex-vivo with Escherichia coli endotoxin before the determination of plasma tumour necrosis factor activity.
Findings
- The highest concentrations of pentoxifylline and its metabolite I occurred 15 minutes after the initial injection. The plasma concentration levels were 9.2 +/- 1.4 and 7.8 +/- 4.3 micrograms/mL respectively.
- The half-life of the pentoxifylline elimination process was 1.44 hours and the volume of distribution was 0.94 L/kg.
- The average plasma concentration of 6-keto-prostaglandin F1 alpha increased over time, showing a significant increase 30 minutes after the bolus administration.
- Additionally, the ex-vivo plasma endotoxin-induced tumour necrosis factor activity significantly decreased at the 1.5 hour and 3 hour marks of the infusion period.
Conclusion
- The results suggest that the infusion of pentoxifylline can increase the presence of 6-keto-prostaglandin F1 alpha and considerly suppress the activity of endotoxin-induced tumour necrosis factor in horses during the infusion period.
Cite This Article
APA
Barton MH, Ferguson D, Davis PJ, Moore JN.
(1998).
The effects of pentoxifylline infusion on plasma 6-keto-prostaglandin F1 alpha and ex vivo endotoxin-induced tumour necrosis factor activity in horses.
J Vet Pharmacol Ther, 20(6), 487-492.
https://doi.org/10.1046/j.1365-2885.1997.00090.x Publication
Researcher Affiliations
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens 30602, USA.
MeSH Terms
- 6-Ketoprostaglandin F1 alpha / blood
- Animals
- Dose-Response Relationship, Drug
- Endotoxins / pharmacology
- Escherichia coli
- Half-Life
- Horses
- Infusions, Intravenous
- Pentoxifylline / blood
- Pentoxifylline / pharmacokinetics
- Pentoxifylline / pharmacology
- Tumor Necrosis Factor-alpha / drug effects
- Tumor Necrosis Factor-alpha / metabolism
Citations
This article has been cited 2 times.- Uney K, Tras B, Corum O, Yildiz R, Maden M. Pharmacokinetics of pentoxifylline and its 5-hydroxyhexyl metabolite following intravenous administration in cattle.. Trop Anim Health Prod 2019 Feb;51(2):435-441.
- Martin EM, Messenger KM, Sheats MK, Jones SL. Misoprostol Inhibits Lipopolysaccharide-Induced Pro-inflammatory Cytokine Production by Equine Leukocytes.. Front Vet Sci 2017;4:160.
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