Pharmacokinetics of methocarbamol and phenylbutazone in exercised Thoroughbred horses

Knych, Heather K.; Stanley, Scott D; Seminoff, Kelsey; McKemie, Daniel S.; Kass, Philip H.

doi:10.1111/jvp.12298

Cited by 8 publications

(7 citation statements)

References 7 publications

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“…The volume of distribution at steady state and clearance of PBZ in this study are in agreement with previous reports 9,17‐19 . Interestingly, in this study PBZ metabolite concentrations were quantifiable for a prolonged period of time, compared with a previous reports conducted by this laboratory 9 .…”

Section: Discussionsupporting

confidence: 93%

“…15,16 If the relative binding affinity of PBZ for plasma proteins is higher, the increase The volume of distribution at steady state and clearance of PBZ in this study are in agreement with previous reports. 9,[17][18][19] Interestingly, in this study PBZ metabolite concentrations were quantifiable for a prolonged period of time, compared with a previous reports conducted by this laboratory. 9 One of the most likely explanations for the differences in detection times between studies is analytical assay sensitivity; however, as the assay used in this study was the same as that used in the previously published study by this laboratory, 9 this would not appear to be the only reason.…”

Section: F I G U R Ementioning

confidence: 69%

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Pharmacokinetics and anti‐inflammatory effects of flunixin meglumine as a sole agent and in combination with phenylbutazone in exercised Thoroughbred horses

Knych

Arthur

McKemie

et al. 2020

Equine Veterinary Journal

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Background: Flunixin meglumine (FM) and phenylbutazone (PBZ) are potent anti-inflammatory agents and as such their potential to mask injuries that would otherwise keep a horse from training or racing is concerning. A common practice in racetrack medicine in the USA is to administer the two drugs within close proximity (24 hours apart) of each other, raising the concern of pharmacokinetic interactions and enhanced anti-inflammatory effects. Objectives: Describe the pharmacokinetics and effects of PBZ on the clearance of FM when administered in close proximity as well as effects on inflammatory mediators. Study design: Two-way randomised balanced crossover experiment. Methods: Twelve Thoroughbred exercised horses received 500 mg FM IV alone or in combination with 2 g of IV PBZ 24 hours later. Blood and urine samples were collected prior to and for up to 120 hours post-drug administration. Whole blood samples were collected at various times and challenged with lipopolysaccharide or calcium ionophore to induce ex vivo synthesis of eicosanoids. Concentrations of FM, PBZ and eicosanoids were measured using LC-MS/MS and noncompartmental pharmacokinetic analysis performed on concentration data. Results: Flunixin meglumine clearance was significantly increased when horses received PBZ 24 hours post-administration (P = .03). No other differences in pharmacokinetic parameters were noted between groups. Thromboxane B 2 was significantly suppressed, relative to baseline for 96 hours post-FM administration. Subsequent administration of PBZ prolonged the suppression. Prostaglandin E2 was decreased for 24 hours following administration of FM with subsequent administration of PBZ prolonging the suppression until 120 hours. PGF 2alpha concentrations were decreased for up to 168 hours post-FM administration. FM administration significantly decreased 15-HETE. Main limitations: Small sample size and lack of a phenylbutazone-only treatment group.

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Section: Discussionsupporting

confidence: 93%

Section: F I G U R Ementioning

confidence: 69%

Pharmacokinetics and anti‐inflammatory effects of flunixin meglumine as a sole agent and in combination with phenylbutazone in exercised Thoroughbred horses

Knych

Arthur

McKemie

et al. 2020

Equine Veterinary Journal

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“…The European Horseracing Scientific Liaison Committee advises a 168‐hour (6‐day) detection time for PBZ, the same detection time as the Fédération Équestre Internationale (FEI) . While its use is prevalent, and it has been well studied in the horse, there is a limited number of comprehensive published studies describing blood and urine concentrations and the pharmacokinetics of this drug and its metabolites in a large population of young horses that are suitable for the establishment of regulatory recommendations.…”

Section: Introductionmentioning

confidence: 99%

Phenylbutazone blood and urine concentrations, pharmacokinetics, and effects on biomarkers of inflammation in horses following intravenous and oral administration of clinical doses

Knych

Arthur

McKemie

et al. 2018

Drug Testing and Analysis

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Phenylbutazone (PBZ) is a potent mon‐steroidal anti‐inflammatory drug used commonly in performance horses. The objectives of the current study were to describe blood and urine concentrations and the pharmacokinetics of PBZ and its metabolites following intravenous (IV) and oral administration and to describe the duration of pharmacodynamic effect. To that end, 17 horses received an IV administration and 18 horses an oral administration of 2 g of PBZ. Blood and urine samples were collected prior to and for up to 96 hours post drug administration. Whole blood samples were collected at various time points and challenged with lipopolysaccharide or calcium ionophore to induce ex vivo synthesis of eicosanoids. Concentrations of PBZ and eicosanoids were measured using liquid chromatography–tandem mass spectrometry (LC–MS/MS) and non‐compartmental pharmacokinetic analysis performed on concentration data from IV and oral administration. Serum concentrations of PBZ and its metabolites were below the limit of quantitation at 96 hours post administration. The volume of distribution at steady state, systemic clearance, and terminal half‐life was 0.194 ± 0.019 L/kg, 23.9 ± 4.48 mL/h/kg, and 10.9 ± 5.32 hours, respectively. The terminal half‐life following oral administration was 13.4 ± 3.01 (paste) and 15.1 ± 3.96 hours (tablets). Stimulation of PBZ treated whole blood with lipopolysaccharide and calcium ionophore resulted in an inhibition of TXB2, PGE2, LTB4 and 15‐HETE production for a prolonged period of time post drug administration. The results of this study suggest that PBZ has a prolonged anti‐inflammatory following IV or oral administration of 2 g to horses.

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“…The author has found that these medications can bring some relief in such instances. Methocarbamol is a centrally acting skeletal muscle relaxant, labelled to reduce muscular spasms [104], and is commonly used as a first-choice drug for these cases. There is a very large dose range for intravenous use of 4.4-55.0 mg/kg.…”

Section: Muscle Relaxantsmentioning

confidence: 99%

Equine Cervical Pain and Dysfunction: Pathology, Diagnosis and Treatment

Story

Haussler

Nout‐Lomas

et al. 2021

Animals

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Interest in the cervical spine as a cause of pain or dysfunction is increasingly becoming the focus of many equine practitioners. Many affected horses are presented for poor performance, while others will present with dramatic, sometimes dangerous behavior. Understanding and distinguishing the different types of neck pain is a starting point to comprehending how the clinical presentations can vary so greatly. There are many steps needed to systematically evaluate the various tissues of the cervical spine to determine which components are contributing to cervical pain and dysfunction. Osseous structures, soft tissues and the central and the peripheral nervous system may all play a role in these various clinical presentations. After completing the clinical evaluation, several imaging modalities may be implemented to help determine the underlying pathologic processes. There are multiple treatment options available and each must be carefully chosen for an individual horse. Provided is a synopsis of the current knowledge as to different disease processes that can result in cervical pain and dysfunction, diagnostic approaches and treatment strategies. Improving the knowledge in these areas will ideally help to return horses to a state of well-being that can be maintained over time and through the rigors of their job or athletic endeavors.

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Pharmacokinetics of methocarbamol and phenylbutazone in exercised Thoroughbred horses

Cited by 8 publications

References 7 publications

Pharmacokinetics and anti‐inflammatory effects of flunixin meglumine as a sole agent and in combination with phenylbutazone in exercised Thoroughbred horses

Pharmacokinetics and anti‐inflammatory effects of flunixin meglumine as a sole agent and in combination with phenylbutazone in exercised Thoroughbred horses

Phenylbutazone blood and urine concentrations, pharmacokinetics, and effects on biomarkers of inflammation in horses following intravenous and oral administration of clinical doses

Equine Cervical Pain and Dysfunction: Pathology, Diagnosis and Treatment

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