Effect of an endurance‐like exercise on the disposition and detection time of phenylbutazone and dexamethasone in the horse: Application to medication control

Authie, E. C.; Garcia, Patrice; Popot, Marie-Agnès; Toutain, Pierre‐Louis; Doucet, Michèle

doi:10.1111/j.2042-3306.2010.00029.x

Cited by 14 publications

(6 citation statements)

References 15 publications

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“…Due to the high degree of plasma protein binding, the ultrafiltration of phenylbutazone through glomerular capillaries into Bowman's capsule fluid is limited to no more than 1-2% of total plasma concentration. The contribution of renal clearance to phenylbutazone elimination was shown to be similar at rest and under test exercise conditions (11.2% and 12.9%, respectively, P > 0.05) (Authié et al, 2010). Of the small fraction of total concentration filtered, some is subsequently reabsorbed, since phenylbutazone is lipophilic.…”

Section: Pharmacokinetics Of Phenylbutazone In the Horsementioning

confidence: 83%

Pharmacokinetics, pharmacodynamics, metabolism, toxicology and residues of phenylbutazone in humans and horses

Lees

Toutain

2013

The Veterinary Journal

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The presence of horse meat in food products destined for human consumption and labelled as beef has raised several concerns of public interest. This review deals solely with one aspect of these concerns; samples of equine tissue from horses destined for the human food chain have tested positive for the non-steroidal anti-inflammatory drug, phenylbutazone. The safety of some or all such foods for human consumers is a major concern, because it was shown many years ago that phenylbutazone therapy in humans can be associated with life threatening blood dyscrasias. As an initial basis for assessing the potential toxicity of foods containing phenylbutazone and its metabolites, this article reviews (1) the pharmacokinetic, pharmacodynamic, metabolic and toxicological profiles of phenylbutazone, with particular reference to horses and humans; (2) toxicity data in laboratory animals; (3) phenylbutazone residues in food producing species, and (4) as a preliminary assessment, the potential hazard associated with the consumption of horse meat containing phenylbutazone and its metabolites. Since phenylbutazone cannot be classified as a carcinogenic substance in humans, and noting that blood dyscrasias in humans are likely to be dose and treatment duration-dependent, the illegal and erratic presence of trace amount residues of phenylbutazone in horse meat is not a public health issue.

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Section: Pharmacokinetics Of Phenylbutazone In the Horsementioning

confidence: 83%

Pharmacokinetics, pharmacodynamics, metabolism, toxicology and residues of phenylbutazone in humans and horses

Lees

Toutain

2013

The Veterinary Journal

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“…interchangeably with blood AUC [8], resulting in errors in the estimation of E h , if the blood: plasma concentration (B:P) ratio is not equal to 1. In other cases, investigators have used plasma…”

Section: Indirect Estimation Of E Hmentioning

confidence: 99%

Application of Organ Clearance to Estimation of the In Vivo Hepatic Extraction Ratio

Mehvar

2016

CCP

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Organ clearance, which has been derived from the organ blood flow and extraction ratio (E), has been extensively used by clinical pharmacologists to explain the pharmacokinetics of many drugs in health and disease. For example, the extent of hepatic clearance or E (Eh) of drugs would determine their response to changes in the liver blood flow and/or activities of the metabolizing enzymes. Although Eh may be obtained directly by cannulating internal blood vessels, the method is invasive. Therefore, indirect methods have been used to estimate Eh from the peripheral blood concentration-time data after intravascular administration of drugs. Additionally, these indirect methods require an estimate of the liver blood flow in the patients or animals. However, some investigators use plasma concentrations and/or liver plasma flow for the estimation of Eh, which could potentially result in significant errors. It is shown here that when plasma concentrations are used along with liver blood flow, an overestimation or underestimation of the true value will result if the blood: plasma concentration (B:P) ratio is >1 or < 1, respectively, with the estimated Eh being different from the true value by a factor equal to the B:P ratio. On the other hand, the use of plasma concentrations and plasma liver flow will always result in an overestimation of the true Eh unless the drug does not penetrate the red blood cells. It is concluded that for the accurate estimation of Eh from the in vivo data, the blood concentration and blood flow should be used.

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“…3 This system reflects a new breath-by-breath approach to the measurement of V̇O 2 in the field (Fig. 1 ) [ 16 ]. Calibration of the system (flowmeter and gas analyzer) was conducted according to the manufacturer’s instructions before each horse was exercised.…”

Section: Methodsmentioning

confidence: 99%

Workload of horses on a water treadmill: effect of speed and water height on oxygen consumption and cardiorespiratory parameters

et al. 2017

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BackgroundDespite the use of water treadmills (WT) in conditioning horses, the intensity of WT exercise has not been well documented. The workload on a WT is a function of water height and treadmill speed. Therefore, the purpose of this study was to determine the effects of these factors on workload during WT exercise.Fifteen client-owned Quarter Horses were used in a randomized, controlled study. Three belt speeds and three water heights (mid cannon, carpus and stifle), along with the control condition (dry treadmill, all three speeds), were tested. Measured outcomes were oxygen consumption (V̇O2), ventilation (respiratory frequency, tidal volume (VT)), heart rate (HR), and blood lactate. An ergospirometry system was used to measure V̇O2 and ventilation. Linear mixed effects models were used to examine the effects of presence or absence of water, water height and speed (as fixed effects) on measured outcomes.ResultsWater height and its interaction with speed had a significant effect on V̇O2, VT and HR, all peaking at the highest water level and speed (stifle at 1.39 m/s, median V̇O2 = 16.70 ml/(kg.min), VT = 6 L, HR = 69 bpm). Respiratory frequency peaked with water at the carpus at 1.39 m/s (median 49 breaths/min). For a given water height, the small increments in speed did not affect the measured outcomes. Post-exercise blood lactate concentration did not change.ConclusionsVarying water height and speed affects the workload associated with WT exercise. The conditions utilized in this study were associated with low intensity exercise. Water height had a greater impact on exercise intensity than speed.

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Effect of an endurance‐like exercise on the disposition and detection time of phenylbutazone and dexamethasone in the horse: Application to medication control

Cited by 14 publications

References 15 publications

Pharmacokinetics, pharmacodynamics, metabolism, toxicology and residues of phenylbutazone in humans and horses

Pharmacokinetics, pharmacodynamics, metabolism, toxicology and residues of phenylbutazone in humans and horses

Application of Organ Clearance to Estimation of the In Vivo Hepatic Extraction Ratio

Workload of horses on a water treadmill: effect of speed and water height on oxygen consumption and cardiorespiratory parameters

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