The effects of pentoxifylline infusion on plasma 6-keto-prostaglandin F(1α) 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 F(1α) were determined. Heparinized whole blood was also incubated ex vivo with 1 ng Escherichia 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 μg/mL, respectively. The half-life of elimination (t( 1/4 β)) of pentoxifylline was 1.44 h and volume of distribution (Vd(area)) was 0.94 L/kg. The mean plasma concentration of 6-keto-prostaglandin F(1α) 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 F(1α) and significantly suppress endotoxin-induced tumour necrosis factor activity in horses during the period of infusion.