Comparative pharmacokinetics of phenylbutazone and its metabolite oxyphenbutazone in clinically normal horses and donkeys.
Abstract: 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.
Publication Date: 1997-01-01 PubMed ID: 8989496
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- Comparative Study
- Journal Article
Summary
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The study compares how phenylbutazone and its metabolite, oxyphenbutazone, are processed in the bodies of horses and donkeys. The results suggest that phenylbutazone disappears more quickly from the blood of donkeys due to faster liver metabolism, implying more frequent dosing may be required for therapeutic effectiveness in donkeys compared to horses.
Methodology
The researchers carried out a comparative pharmacokinetics study to evaluate how phenylbutazone and its metabolite, oxyphenbutazone, are processed in clinically normal horses and donkeys.
- The study used 4 clinically normal horses and 6 clinically normal donkeys.
- Phenylbutazone was administered intravenously to each animal. Blood samples were collected at different time intervals ranging from 0 to 480 minutes post-administration.
- Serum from the blood samples was analyzed in triplicate using high-performance liquid chromatography to determine the concentrations of phenylbutazone and oxyphenbutazone.
- Pharmacokinetic variables were separately analyzed for each horse and donkey using the serum concentration-time curve.
Results
The study revealed several significant differences in the pharmacokinetics of phenylbutazone and oxyphenbutazone between horses and donkeys.
- The total body clearance of phenylbutazone in horses was found to be five times lower than that in donkeys.
- Pharmacokinetic variables such as area under the curve (AUC – a measure of drug exposure over time) and mean residence time (MRT – average time the drug stays in the body) were significantly greater in horses than in donkeys.
- Surprisingly, there was no significant difference found between the apparent volume of distribution (Vd – a measure of how widely the drug is distributed in body tissues) in horses and donkeys.
- For oxyphenbutazone, the time to reach peak concentration was significantly less in donkeys than in horses.
Conclusion
Based on the results, the researchers concluded that:
- Phenylbutazone is cleared more rapidly from the bodies of donkeys than horses due to faster liver metabolism. This also leads to quicker appearance of oxyphenbutazone in the serum.
- Given that phenylbutazone concentration decreases more rapidly in donkeys after a single dose, more frequent administration may be necessary for achieving therapeutic efficacy in donkeys compared to horses.
Cite This Article
APA
Mealey KL, Matthews NS, Peck KE, Ray AC, Taylor TS.
(1997).
Comparative pharmacokinetics of phenylbutazone and its metabolite oxyphenbutazone in clinically normal horses and donkeys.
Am J Vet Res, 58(1), 53-55.
Publication
Researcher Affiliations
- Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station 77840, USA.
MeSH Terms
- Animals
- Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
- Anti-Inflammatory Agents, Non-Steroidal / blood
- Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
- Area Under Curve
- Chromatography, High Pressure Liquid / veterinary
- Equidae / metabolism
- Equidae / physiology
- Female
- Horses / metabolism
- Horses / physiology
- Injections, Intravenous / veterinary
- Male
- Oxyphenbutazone / administration & dosage
- Oxyphenbutazone / blood
- Oxyphenbutazone / pharmacokinetics
- Phenylbutazone / administration & dosage
- Phenylbutazone / blood
- Phenylbutazone / pharmacokinetics
- Time Factors
Citations
This article has been cited 4 times.- O O, Simon BT, Ebner LS, Lizarraga I, Sun X, Cox SK. The pharmacokinetics and pharmacodynamics of midazolam after intravenous administration to donkeys (Equus africanus asinus). Can J Vet Res 2022 Apr;86(2):125-131.
- Boocock H, Flyps J, Escobar A, Redondo JI, Taylor PM, Gozalo-Marcilla M, Johnston GM, Bettschart-Wolfensberger R, Sullivan R. Donkey and Hybrid Anaesthetic Mortality in an Observational, Prospective, Multicentre Cohort Study. Animals (Basel) 2025 Jun 25;15(13).
- Yang B, Liu S, Cheng J, Qu H, Guo Y, Ji C, Wang Y, Zhao S, Huang S, Zhao L, Ma Q. Pharmacokinetics of Enrofloxacin in Plasma, Urine, and Feces of Donkey (Equus asinus) after a Single Intragastric Administration. Antibiotics (Basel) 2024 Apr 12;13(4).
- Buono F, Veneziano V, Veronesi F, Molento MB. Horse and donkey parasitology: differences and analogies for a correct diagnostic and management of major helminth infections. Parasitology 2023 Oct;150(12):1119-1138.
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