Comparative pharmacokinetics of phenylbutazone and its metabolite oxyphenbutazone in clinically normal horses and donkeys.
OBJECTIVE
To compare plasma disposition of phenylbutazone and its metabolite oxyphenbutazone after i.v. administration of phenylbutazone in horses and donkeys.


METHODS
4 clinically normal horses and 6 clinically normal donkeys.


METHODS
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).


CONCLUSIONS
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.


CONCLUSIONS
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.
Mealey
K L
KL
Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station 77840, USA.
Matthews
N S
NS
Peck
K E
KE
Ray
A C
AC
Taylor
T S
TS
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D018397:Equidae / Q000378:metabolism* / Q000502:physiology; D005260:Female; D006736:Horses / Q000378:metabolism* / Q000502:physiology; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D010113:Oxyphenbutazone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D010653:Phenylbutazone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010653:Phenylbutazone; D010113:Oxyphenbutazone