THE EFFECTS OF PENTOXIFYLLINE INFUSION ON PLASMA 6-KETO-PROSTAGLANDINF1-ALPHA AND EX-VIVO ENDOTOXIN-INDUCED TUMOR-NECROSIS-FACTOR ACTIVITYIN 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 fo r 24 h. Plasma was separated and concentrations of pentoxifylline, its reduced metabolite I, and 6-keto-prostaglandin F-1 alpha were determi ned. Heparinized whole blood was also incubated ex vivo with 1 ng Esch erichi coli endotoxin/mL blood for 6 h before determination of plasma tumour necrosis factor activity. The peak plasma concentrations of pen toxifylline and metabolite I occurred at 15 min after bolus injection and were 9.2 +/- 1.4 and 7.8 +/- 4.3 mu g/mL, respectively, The half-l ife of elimination (t(1/2 beta)) of pentoxifylline was 1.44 h and volu me of distribution (Vd(area)) was 0.94 L/kg. The mean plasma concentra tion of 6-keto-prostaglandin F-1 alpha increased over time, with a sig nificant increase occurring 30 min after the bolus administration, Ex vivo plasma endotoxin-induced tumour necrosis factor activity was sign ificantly decreased at 1.5 and 3 h of infusion, These results indicate that infusion of pentoxifylline will increase 6-keto-prostaglandin F- 1 alpha and significantly suppress endotoxin-induced tumour necrosis f actor activity in horses during the period of infusion.