Phenylbutazone and oxyphenbutazone distribution into tissue fluids in the horse.

The clinically recommended dose rate of phenylbutazone (4.4 mg/kg) was administered intravenously as a single dose to five Welsh Mountain ponies. Distribution of phenylbutazone and its active metabolite oxyphenbutazone into body fluids was studied by measuring concentrations in plasma, tissue-cage fluid, peritoneal fluid and acute inflammatory exudate harvested from a polyester sponge model of inflammation. The ready penetration of phenylbutazone into inflammatory exudate was demonstrated by the relatively high mean value for Cmax of 12.4 micrograms/ml occurring at a time of 4.6 h and a mean AUC0-24 of 128 microgram X h/ml. A high mean exudate:plasma AUC0-24 ratio of 0.83 was recorded. Plasma:exudate concentration ratios for phenylbutazone were initially greater than and subsequently less than one; the slower clearance from exudate was indicated by approximate t1/2 beta) values of 4.8 and 24 h for plasma and exudate, respectively. These findings may help to explain the relatively long duration of action of phenylbutazone, in spite of a plasma elimination half-life of less than 5 h. Lower values of Cmax and AUC0-24 for phenylbutazone passage into peritoneal fluid (6.3 micrograms/ml and 45 micrograms X h/ml) were recorded, and a limited number of sampling times indicated a similar degree of penetration as into tissue cage fluid. Mean concentrations of oxyphenbutazone in all fluids were lower than phenylbutazone concentrations at all times, but ready penetration of the metabolite into body fluids, especially into inflammatory exudate, occurred suggesting that oxyphenbutazone may contribute to the anti-inflammatory effect. The hyperaemia of acute inflammation and the high protein levels in inflammatory exudate may both assist passage of phenylbutazone and oxyphenbutazone into exudate.