The effects of pentoxifylline infusion on plasma 6-keto-prostaglandin F1 alpha and ex vivo endotoxin-induced tumour necrosis factor activity in horses.
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.
Barton
M H
MH
Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens 30602, USA.
Ferguson
D
D
Davis
P J
PJ
Moore
J N
JN
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D006207:Half-Life; D006736:Horses; D007262:Infusions, Intravenous; D010431:Pentoxifylline / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects* / Q000378:metabolism
D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D015121:6-Ketoprostaglandin F1 alpha; D010431:Pentoxifylline