Comparative effects of phenylbutazone, naproxen and flunixin meglumine on equine platelet aggregation and platelet factor 3 availability in vitro

Abstract

Nonsteroidal anti-inflammatory drugs are commonly used in the treatment of inflammatory conditions, and have potential value in the treatment of thrombotic disease in the horse. This study compares the potency of three nonsteroidal anti-inflammatory drugs phenylbutazone, naproxen (equiproxen) and flunixin meglumine (banamine) with respect to their effects on equine platelets. Two functional responses of horse platelets were evaluated in vitro: their ability to aggregate and their ability to make available platelet factor 3 procoagulant activity. Flunixin at a concentration of 10(-6) M significantly depressed the maximum degree of adenosine diphosphate-induced (10(-6)M) aggregation while much higher concentrations of phenylbutazone and naproxen (5 X 10(5)M) were required to produce similar effects. None of the non-steriodal anti-inflammatory drugs significantly affected the duration of the lag phase or the initial velocity of adenosine diphosphate-induced aggregation within the range of drug concentrations used (10(-6)-10(-3)M). The lag phase and initial velocity of acid-soluble collagen-induced aggregation were significantly affected by 10(-6) M flunixin and 10(-4) M phenylbutazone or naproxen was required to produce equivalent effects. Concentrations of 5 X 10(-6) M flunixin and 5 X 10(-4) M phenylbutazone or naproxen were required to significantly depress the degree of collaen-induced aggregation of horse platelets. Although the effects of the nonsteroidal anti-inflammatory drugs were qualitatively similar, flunixin was a much more potent inhibitor of platelet aggregation than either of the other two drugs (which were equipotent). At very high drug concentrations (5 X 10(-4) M and greater), all three drugs produced the same degree of inhibition of equine platelet aggregation. Platelet factor 3 activity was made available by exposing horse platelets to 10(-5) M adenosine diphosphate or 1:800 acid-soluble collagen; but not by exposure to a suspension of kaolin particles. Only a small portion of the total platelet factor 3 activity was made available on stimulation with either adenosine diphosphate or collagen. Pretreatment of horse platelets with any of the nonsteroidal anti-inflammatory drugs (10(-4) M concentration) had no significant effect on adenosine diphosphate or collagen-induced platelet factor 3 availability.