Population distributions of phenylbutazone and oxyphenbutazone after oral and i.v. dosing in horses

Experiments to determine the residual plasma concentrations of phenylbutazone and its metabolites found in horses racing on a ‘no‐race day medication’ or 24‐h rule were carried out. One dosing schedule (oral‐i.v.) consisted of 8.8 mg/kg (4g/1000 lbs) orally for 3 days, followed by 4.4 mg/kg (2g/1000 lbs) intravenously on day 4. A second schedule consisted of 4.4 mg/kg i.v. for 4 days. The experiments were carried out in Thoroughbred and Standardbred horses at pasture, half‐bred horses at pasture, and in Thoroughbred horses in training. After administering the i.v. schedule for 4 days to Thoroughbred and Standard‐bred horses at pasture, the mean plasma concentrations of phenylbutazone increased from 0.77 μg/ml on day 2 to 2.5 μg/ml on day 5. The shape of the frequency distribution of these populations was log‐normal. These data are consistent with one horse in 1,000 yielding a plasma level of 8.07 μg/ml on day 5. After administration of the oral‐i.v. schedule to Thoroughbred and Standard‐bred horses at pasture, the mean plasma concentrations of phenylbutazone were 3.4 μg/ml on day 2 and 3.5μg/ml on day 5. The range on day 5 was from 1.4 to 8.98 μg/ml and the frequency distribution was log‐normal. These data are consistent with one horse in 1000 having a plasma level of 15.8 μg/ml on day 5. In a final experiment, the oral dosing schedule was administered to 62 Thoroughbred horses in training. Plasma concentrations on day 5 in these horses averaged 5.3 μg/ml. The range was from 1.3 to 13.6 μg/ml and the frequency distribution was log‐normal. Statistical projection of these values suggests that following this oral dosing schedule in racing horses about one horse in 1000 will yield a plasma level of 23.5 μg/ml of phenylbutazone 24h after the last dose.