Comparative pharmacokinetics of phenylbutazone and its metabolite oxyphenbutazone in clinically normal horses and donkeys.

Abstract

OBJECTIVE:

To compare plasma disposition of phenylbutazone and its metabolite oxyphenbutazone after i.v. administration of phenylbutazone in horses and donkeys.

ANIMALS:

4 clinically normal horses and 6 clinically normal donkeys.

PROCEDURE:

Blood samples were collected from each animal at time 0 (before) and 5, 10, 20, 30, 45, 60, 90, 120, 180, 240, 300, 360, and 480 minutes after i.v. administration of a bolus dose of phenylbutazone. Serum was analyzed in triplicate by use of high-performance liquid chromatography for determination of phenylbutazone and oxyphenbutazone concentrations. The serum concentration-time curve for each horse and donkey was analyzed separately to estimate model-independent pharmacokinetic variables.

RESULTS:

Significant differences were found in several pharmacokinetic variables of phenylbutazone and oxyphenbutazone in horses, compared with donkeys. Mean total body clearance of phenylbutazone in horses was fivefold less than that in donkeys (29.3 and 170.3 ml/kg/h, respectively). Mean values for area under the curve and mean residence time in horses (118.3 micrograms/h/ml and 3.6 hours, respectively) were significantly greater than values in donkeys (28.3 micrograms/h/ml and 1.7 hours, respectively). Mean values for apparent volume of distribution at steady state were not significantly different between horses and donkeys. For oxyphenbutazone, mean time to peak concentration in donkeys was significantly less than that in horses (1.6 and 6.4 hours, respectively).

CONCLUSION:

Phenylbutazone clearance in donkeys was higher than that in horses, and appearance of the metabolite oxyphenbutazone in serum was more rapid in donkeys than in horses, indicating that hepatic metabolism of phenylbutazone is more rapid in donkeys than in horses.

CLINICAL RELEVANCE:

Because serum concentration of phenylbutazone after single i.v. bolus administration (4.4 mg/kg of body weight) decreases more rapidly in donkeys, compared with horses, phenylbutazone may require more frequent administration in donkeys to achieve therapeutic efficacy.

• Authors: K L Mealey, N S Matthews, K E Peck, A C Ray, T S Taylor
• Journal: American journal of veterinary research (Am J Vet Res) Vol. 58 Issue 1 Pg. 53-5 (Jan 1997) ISSN: 0002-9645 [Print] United States
• PMID: 8989496 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Phenylbutazone
• Oxyphenbutazone

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, blood, pharmacokinetics)
• Area Under Curve
• Chromatography, High Pressure Liquid (veterinary)
• Equidae (metabolism, physiology)
• Female
• Horses (metabolism, physiology)
• Injections, Intravenous (veterinary)
• Male
• Oxyphenbutazone (administration & dosage, blood, pharmacokinetics)
• Phenylbutazone (administration & dosage, blood, pharmacokinetics)
• Time Factors