Comparative pharmacokinetics of phenylbutazone in young and geriatric horses

Comparative pharmacokinetics of phenylbutazone in healthy young-adult and geriatric horses

Am J Vet Res. 2024 Jun 28:1-8. doi: 10.2460/ajvr.24.01.0012. Online ahead of print.
Authors
Iman Y Zaghloul 1 , Daniela Bedenice 2 , Michelle L Ceresia 1 2 , Pilar Hermida Jones 2 , Alfredo Sanchez-Londono 3 , Mitchell N Lobo 1 , Mark Böhlke 1 , Mary Rose Paradis 2
Affiliations

1 Department of Pharmaceutical Sciences and Department of Pharmacy Practice, Massachusetts College of Pharmacy and Health Sciences University, Boston, MA.
2 Department of Clinical Sciences and Department of Environmental and Population Health, Cummings School of Veterinary Medicine at Tufts University, Grafton, MA.
3 Currently: Equine Field Service, Auburn University, Auburn, AL.

PMID: 38942059
DOI: 10.2460/ajvr.24.01.0012

Abstract

Objective: 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.

Animals: 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. Clinical relevance: 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. Keywords: age; equine; geriatric; pharmacokinetics; phenylbutazone.