Comparative pharmacokinetics of phenylbutazone in healthy young-adult and geriatric horses.
Abstract: To evaluate the effects of aging on phenylbutazone (PBZ) disposition in older horses (≥ 25 years old) compared to young adults (4 to 10 years old) by characterizing the pharmacokinetic profile of PBZ and its active metabolite, oxyphenbutazone (OPBZ), following a 2.2-mg/kg dose, IV. We hypothesized that the disposition of PBZ will be affected by age. Methods: 16 healthy horses (8 young adults aged 4 to 10 years and 8 geriatric horses ≥ 25 years old). Methods: Horses were administered a single 2.2-mg/kg PBZ dose, IV. Plasma samples were collected at designated time points and frozen at -80 °C until assayed using liquid chromatography-tandem mass spectrometry. Pharmacokinetic analyses were performed using Phoenix WinNonlin, version 8.0 (Certara). Both clinical and pharmacokinetic data were compared between age groups using independent samples t tests, with P < .05 considered significant. Results: Baseline characteristics did not differ between groups, with the exception of age, weight, and plasma total solids. Plasma concentrations of PBZ were best described by a two-compartment model. The maximum plasma concentration of OPBZ was reached at 5 hours for both age groups, and the metabolite-to-parent-drug area-under-the-curve ratios were approximately 20% for both groups. None of the pharmacokinetic parameters of PBZ or its metabolite, OPBZ, differed significantly between age groups. Conclusions: The hypothesis was rejected as there was no significant difference in PBZ disposition in young-adult horses compared to geriatric horses. Our data do not support the need for dose adjustments of PBZ in clinically healthy geriatric horses.
Publication Date: 2024-06-28 PubMed ID: 38942059DOI: 10.2460/ajvr.24.01.0012Google Scholar: Lookup
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- Journal Article
- Comparative Study
Summary
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The research tests how aging effects the disposition of a commonly used drug, phenylbutazone (PBZ), in horses. It compared young adult horses to geriatric horses and found no significant differences, indicating no changes to dosage is necessary in older horses.
Research Purpose and Hypothesis
- The study aimed to investigate the effects of aging on drug disposition in horses, specifically looking at the drug phenylbutazone (PBZ).
- The researchers hypothesized that the age of horses would affect the disposition of PBZ, with the older horses possibly needing different doses than the younger ones.
Methodology
- 16 healthy horses were studied, with half being young adults aged 4 to 10 years and half being geriatric horses aged 25 years or older.
- Each horse was administered a single 2.2-mg/kg PBZ dose intravenously.
- Plasma samples were taken from the horses at designated time points and then stored at -80°C until they were assayed using liquid chromatography-tandem mass spectrometry.
- Pharmacokinetic analyses were performed using Phoenix WinNonlin, version 8.0 (Certara).
- Different data, both clinical and pharmacokinetic, were compared between the two age groups using independent samples t tests, with P < .05 considered significant.
Results
- The baseline characteristics did not differ significantly between the two groups of horses, except for age, weight, and plasma total solids.
- Plasma concentrations of PBZ were best described using a two-compartment model.
- The maximum plasma concentration of OPBZ, the active metabolite of PBZ, was reached at the same time in both age groups – 5 hours post administration.
- The metabolite-to-parent-drug area-under-the-curve ratios were similar for both groups, at approximately 20%.
- No significant differences were found between the two age groups in terms of the pharmacokinetic parameters of either PBZ or its metabolite, OPBZ.
Conclusion
- The researchers’ initial hypothesis was rejected because their data showed no significant difference in how PBZ is disposed in young-adult horses versus geriatric horses.
- Based on the results, they concluded that there is no need for dose adjustments when giving PBZ to clinically healthy geriatric horses.
Cite This Article
APA
Zaghloul IY, Bedenice D, Ceresia ML, Jones PH, Sanchez-Londono A, Lobo MN, Böhlke M, Paradis MR.
(2024).
Comparative pharmacokinetics of phenylbutazone in healthy young-adult and geriatric horses.
Am J Vet Res, 85(8).
https://doi.org/10.2460/ajvr.24.01.0012 Publication
Researcher Affiliations
- Department of Pharmaceutical Sciences and Department of Pharmacy Practice, Massachusetts College of Pharmacy and Health Sciences University, Boston, MA.
- Department of Clinical Sciences and Department of Environmental and Population Health, Cummings School of Veterinary Medicine at Tufts University, Grafton, MA.
- Department of Pharmaceutical Sciences and Department of Pharmacy Practice, Massachusetts College of Pharmacy and Health Sciences University, Boston, MA.
- Department of Clinical Sciences and Department of Environmental and Population Health, Cummings School of Veterinary Medicine at Tufts University, Grafton, MA.
- Department of Clinical Sciences and Department of Environmental and Population Health, Cummings School of Veterinary Medicine at Tufts University, Grafton, MA.
- Currently: Equine Field Service, Auburn University, Auburn, AL.
- Department of Pharmaceutical Sciences and Department of Pharmacy Practice, Massachusetts College of Pharmacy and Health Sciences University, Boston, MA.
- Department of Pharmaceutical Sciences and Department of Pharmacy Practice, Massachusetts College of Pharmacy and Health Sciences University, Boston, MA.
- Department of Clinical Sciences and Department of Environmental and Population Health, Cummings School of Veterinary Medicine at Tufts University, Grafton, MA.
MeSH Terms
- Animals
- Horses / metabolism
- Horses / blood
- Phenylbutazone / pharmacokinetics
- Phenylbutazone / blood
- Aging
- Male
- Female
- Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
- Anti-Inflammatory Agents, Non-Steroidal / blood
- Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
- Area Under Curve
- Half-Life
- Age Factors
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