Pharmacokinetic and pharmacodynamic studies on phenylbutazone and oxyphenbutazone in goats

Abstract

Phenylbutazone was administered intravenously and orally to six goats as a single dose of 4.4 mg/kg and its disposition and bioavailability and the disposition of its active metabolite, oxyphenbutazone, in plasma were investigated. The effect of the administration of the drug of oxyphenbutazone on ex vivo serum thromboxane (TX)B2 generation in platelets was also studied. Phenylbutazone was eliminated slowly with mean (se) elimination half-lives (t1/2 beta) of 15.3 (1.15) hours and 22.0 (3.32) hours after intravenous and oral administration, respectively. The bioavailability of phenylbutazone paste administered orally was 61 (7) per cent (corrected by the t1/2 beta) and relatively slow absorption was observed, as indicated by a time of maximum drug concentration (tmax) of 3.47 (0.39) hours and a mean absorption time (MAT) of 10.4 (8.61) hours. The concentration of oxyphenbutazone in plasma was low and the ratio of the areas under the curve (AUC) of oxyphenbutazone to phenylbutazone was approximately 0.02:1 after both intravenous and oral administration. Thromboxane B2 generation in the platelets was significantly inhibited (P < 0.05) from one to 12 hours after intravenous administration and from two to 12 hours after oral administration. The results suggest that phenylbutazone is a potentially useful non-steroidal anti-inflammatory drug for use in goats by either route of administration.