The effects of pentoxifylline infusion on plasma 6‐keto‐prostaglandin F_1α 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.

Intravenous pentoxifylline does not affect the exercise‐induced pulmonary arterial, capillary or venous hypertension in Thoroughbred horses

“…These observations are similar to those reported previously and are probably a manifestation of the pentoxifylline‐induced phosphodiesterase inhibition at various tissue sites (Barton et al , 1997). The dosage/administration regimen of pentoxifylline in our experiments was based on previous work (Crisman et al , 1993; Barton et al , 1997) demonstrating that peak plasma concentrations of pentoxifylline and its metabolite I—which is rheologically active (Ambus et al , 1990; Ward & Crisold, 1987)—occurred 15 min after bolus injection in horses. The in vivo concentration of pentoxifylline thus achieved is also believed to be effective in improving equine RBC deformability in vitro (Weiss et al , 1994).…”

“…administration of pentoxifylline in our experiments were its known poor/erratic absorption from the equine gastrointestinal tract and the significantly lower plasma concentrations achieved after oral administration (Crisman et al , 1993). Besides eliciting rheologic effects (Geor et al , 1992; Weiss et al , 1994; Weiss & Smith, 1998), pentoxifylline administration in horses increases circulating prostaglandin concentrations and suppresses formation of endotoxin‐induced tumor‐necrosis factor (Barton et al , 1997). Although in vitro beneficial rheologic effects of pentoxifylline have been described (Geor et al , 1992; Weiss et al , 1994), the effective plasma concentration of the drug and its metabolite(s) as well as the precise duration for which the drug must be administered to achieve these effects remain unknown.…”

Effects of pentoxifylline on pulmonary function and results of cytologic examination of bronchoalveolar lavage fluid in horses with recurrent airway obstruction

“…12,13,[18][19][20] Rheologic and anti-inflammatory effects of PTX have led to its use as a therapeutic agent for various diseases in horses, including navicular disease, 21 exerciseinduced pulmonary hemorrhage, 21,22 and endotoxemia. [23][24][25][26] Pentoxifylline is approved in Canada for use in the treatment of horses with navicular disease. l Pentoxifylline also has bronchodilatator properties.…”

Equine endotoxaemia ‐ A state‐of‐the‐art review of therapy

“…74 Similarly, administration of 7.5 mg/kg IV followed by an infusion of 3 mg/kg/h resulted in a brief peak blood concentration of 9.6 mg/mL with a steady state concentration of 3.4 mg/kg. 75 As such, although pentoxifylline may be beneficial in endotoxaemia and the potential usefulness of this has been demonstrated in vitro, it is unlikely to have any significant effect when given IV at currently recommended doses. Furthermore the oral bioavailability of pentoxifylline has been demonstrated to be very poor and erratic 74 and no accurate recommendations can be made regarding its oral use on the basis of currently available information.…”