Biochemical and haematological effects of phenylbutazone in horses

Abstract

Summary Five matched pairs of horses were used to investigate the effects of phenylbutazone on a range of physiological, biochemical and haematological variables. The drug was given by mouth daily for 15 consecutive days at the manufacturer's recommended dose rates to one group of horses (Group A); the second group (Group B) received equivalent doses of a placebo. For some of the measured parameters, significant changes were recorded in both groups, indicating background instability. Significant decreases in serum total protein, albumin, plasma pH, viscosity and magnesium, and an increase in albumin: globulin ratio occurred in Group A, but not in Group B. These changes were, therefore, attributed to phenylbutazone or its metabolites. Toxicologically, the change in pH is probably unimportant but the decrease in protein concentration may have resulted from a protein losing enteropathy and/or from decreased synthesis in the liver. In one animal which received phenylbutazone, clinical signs of toxicity (lethargy, inappetance, oedema) were observed and evidence of hepatotoxicity and haematological changes were also noted in this horse. It is concluded that recommended dose rates of phenylbutazone should never be exceeded and that the period for which the highest dose (4.4 mg/kg body weight twice daily for four days) is administered should be reduced. In clinical cases, where phenylbutazone toxicity is suspected, measurement of serum or plasma protein concentration might provide an indication of the need to reduce dose levels or stop therapy. Résumé Cinq paires de chevaux comparables ont été utilisés pour rechercher les effets de la phénylbutazone sur un ensemble de variables physiologiques, biochimiques, hématologiques. Le médicament fut administréà un groupe de chevaux (Groupe A), par voie orale, chaque jour durant 15 jours consécutifs; on respectait les posologies recommandées par le fabricant. Un second groupe (Groupe B) recut dans les mêmes conditions un placebo. Pour quelques paramètres, des changements significatif furent constatés dans les deux groupes ce qui indique une instabilité des conditions fixes de l'expérience. Au sein du Groupe A, une diminution significative s̀e produisit pour les protéines totales, pour l'albumine, pour le pH plasmatique, pour la viscosité et pour le magnésium plasmatiques et une augmentation dans le rapport globuline albumines. Les modifications ne se produisirent point au sein du Groupe B. Les changements furent en conséquence attribués à la phénylbutazone ou a ses métabolites. Sur le plan toxicologique, la variation du pH est probablement sans importance; l'abaissement de la concentration en protéines peut résulter d'une entéropathie spoliatrice ou (et) d'une synthèse hépatique diminuée. Chez un animal recevant de la phénylbutazone, des signes cliniques de toxicité (léthargie, oedème et inappétence) furent observés; des signes d'hépatotoxicité et des sanguines furent remarqués chez ce cheval. On en conclue que les posologies recommandées pour la phénylbutazone ne devraient jamais...

Clinical pharmacology and therapeutic uses of non‐steroidal anti‐inflammatory drugs in the horse

“…When phenylbutazone was given to three-to-10-monthold foals (10 mg/kg bwt daily for 12 to 42 days) nine out of 10 showed no clinical signs although endoscopic and radiographic ante mortem and subsequent post mortem examinations showed a high incidence of ulceration (Traub et al 1983a). In view of the authors' experience with phenylbutazone in aged horses (Lees et al 1983a) it would seem worthwhile examining the effect of age on susceptibility to the toxic effects of the drug. Although Snow et al(1981b) have concluded that there were breed differences in the susceptibility of horses to the toxic effects of phenylbutazone, and that pony breeds are more susceptible than Thoroughbreds, it is possible that the lack of clinical signs of toxicity in Thoroughbreds could have been because of the lower doses of phenylbutazone given (8.2 mg/kg bwt daily in two doses for 13 days compared with 12 mg/kg bwt fed in two equal doses to ponies for eight to 10 days).…”

A toxicity study of eltenac, a nonsteroidal anti‐inflammatory drug, in horses

“…However, urinalysis did not show significant increases of protein in the urine at the time of peripheral hypoproteinaemia. A protein‐losing gastroenteropathy has been documented in toxicity studies of phenylbutazone in the horse ( Snow et al ., 1979 ; Lees et al ., 1983 ; MacKay et al ., 1983 ). Faecal losses of plasma albumin, using a 51Cr‐labelled plasma albumin technique, were shown in ponies given large doses of phenylbutazone (8–12 mg/kg for 8 days) ( Snow et al ., 1981 ).…”

Gelatinous Marrow Transformation and Hematopoietic Atrophy in a Miniature Horse Stallion

“…23 In horses, reports of hematologic effects of phenylbutazone are mixed. 14,15,17,19,24,26 Decreased albumin concentration, attributed to gastrointestinal loss, 14,17,19,24 and neutropenia, associated with a much higher dose of phenylbutazone administered over a longer time, were reported. 19 Hence, although it is possible that phenylbutazone had toxic effects on granulopoiesis in this horse, it was considered unlikely.…”