Biochemical and haematological effects of a revised dosage schedule of phenylbutazone in horses

Taylor, JB; Walland, A; Lees, P.; Gerring, E. L.; Maitho, Timothy; Millar, J. H.

doi:10.1136/vr.112.26.599

Cited by 18 publications

(10 citation statements)

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“…Recently, phenylbutazone was given to five aged Thoroughbreds and Hunters for 15 days (4.4 mg/kg bwt twice daily for four days; 2.2 mg/kg bwt twice daily for four days; 2.2 mg/kg bwt once daily for seven days) and a reduction in plasma protein levels averaging 16 per cent was recorded (Lees et al 1983a). In a second study, the first phase of dosing was reduced from 4.4 mg/kg bwt twice daily for four days to one day and no clinical toxicity or toxicological changes in plasma and blood biochemistry were noted (Taylor et al 1983). These findings are consistent with clinical reports of horses receiving long term low maintenance doses of phenylbutazone which do not rise above the threshold for toxicity.…”

Section: Phenylbutazonementioning

confidence: 99%

Clinical pharmacology and therapeutic uses of non‐steroidal anti‐inflammatory drugs in the horse

Lees

Higgins

1985

Equine Veterinary Journal

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141

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Summary Weak organic acids possessing anti‐inflammatory, analgesic and antipyretic properties — commonly known as aspirin‐like drugs — have been used in equine medicine for almost 100 years. These non‐steroidal anti‐inflammatory drugs (NSAIDs) may be classified chemically into two groups; the enolic acids such as phenylbutazone and carboxylic acids like flunixin, meclofenamate and naproxen. All NSAIDs have similar and possibly identical modes of action accounting for both their therapeutic and their toxic effects. They block some part of the cyclo‐oxygenase enzyme pathway and thereby suppress the synthesis of several chemical mediators of inflammation, collectively known as eicosanoids. The available evidence indicates that some of the newer NSAIDs have a reasonable safety margin but further studies are required. The toxicity of phenylbutazone in the horse has been investigated very thoroughly in recent years and it has been shown to cause renotoxicity and, most significantly, ulceration of the gastrointestinal tract when relatively high doses are administered. Several factors may predispose towards phenylbutazone toxicity in the horse, including breed and age, but high dosage is considered to be particularly important. The absorption into, and fate within, the body of NSAIDs are considered and particular attention is drawn to the ways in which these pharmacokinetic properties relate to the drugs' toxicity and clinical efficacy. In reviewing current knowledge of the clinical pharmacology of this important group of drugs, it is hoped to provide the clinician with a rational, scientific basis for their safe and effective use in equine practice.

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Section: Phenylbutazonementioning

confidence: 99%

Clinical pharmacology and therapeutic uses of non‐steroidal anti‐inflammatory drugs in the horse

Lees

Higgins

1985

Equine Veterinary Journal

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141

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“…This was attributed to a protein losing enteropathy, and hepatotoxicity and ventral abdominal oedema were also recorded. However, reduction of the dosage to 4.4 mg/ kg daily provided clinical efficacy without significant toxicity in horses (Taylor et al, 1983). These detailed equine studies together with extensive clinical experience with phenylbutazone in this species indicate (a) that the margin between therapeutic and toxic doses is narrow, doses only moderately in excess of those recommended for therapy producing life-threatening sideeffects and (b) that the drug can be used effectively and safely over prolonged periods provided that the daily dosage is restricted.…”

Section: Introductionmentioning

confidence: 98%

Phenylbutazone Pharmacokinetics and Bioavailability in the Dromedary Camel (Camelus Dromedarius)

Kadir

Ali²,

Hadrami

et al. 1997

Vet Pharm & Therapeutics

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Phenylbutazone was administered intravenously and intramuscularly at a dosage rate of 4.4 mg/kg to a group of 6 female camels in a two-period crossover study. After intravenous (i.v.) administration, disposition was characterised by a two-compartment open model, with a low volume of distribution (0.174 l.kg-1), and distribution and elimination half-lives of 0.43 and 12.51 h, respectively. After intramuscular (i.m.) dosing absorption was relatively rapid with absorption half-time and time of maximal concentration values of 1.14 and 3.95 h, respectively. Plateau concentrations of phenylbutazone in plasma were obtained between 2 and 12 h and mean bioavailability was 97%, although this was subject to wide inter-animal differences. Plasma concentrations of the phenylbutazone metabolite, oxyphenbutazone, were low after iv dosing and generally undetectable after im administration, indicating that it is unlikely to contribute significantly to the pharmacological effects produced by phenylbutazone administration. An indication was obtained that phenylbutazone inhibited the ex vivo synthesis of serum thromboxane B2 (TxB2) for 24h after i.v. dosing, but this finding requires confirmation.

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“…23 In horses, reports of hematologic effects of phenylbutazone are mixed. 14,15,17,19,24,26 Decreased albumin concentration, attributed to gastrointestinal loss, 14,17,19,24 and neutropenia, associated with a much higher dose of phenylbutazone administered over a longer time, were reported. 19 Hence, although it is possible that phenylbutazone had toxic effects on granulopoiesis in this horse, it was considered unlikely.…”

Section: Discussionmentioning

confidence: 99%

Gelatinous Marrow Transformation and Hematopoietic Atrophy in a Miniature Horse Stallion

et al. 2010

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Gelatinous marrow transformation, or serous atrophy of bone marrow fat, has been noted in livestock, laboratory animals, and wildlife in association with an inadequate plane of nutrition, inanition, or intoxication. This is a report of gelatinous marrow transformation and hematopoietic marrow atrophy in a 5-year-old miniature horse stallion. The horse had oral malformations leading to poor food assimilation and emaciation. A bone marrow biopsy obtained to investigate persistent anemia and leukopenia showed hematopoietic atrophy and replacement of fat with a granular extracellular substance, which stained with alcian blue, consistent with acidic mucopolysaccharide content. Surgical correction of the dental abnormalities resulted in improved food assimilation, weight gain, and resolution of cytopenias. In humans, gelatinous bone marrow transformation and hematopoietic atrophy are commonly associated with malnutrition from anorexia nervosa and other causes. The cause of hematopoietic atrophy is unknown but may relate to a nonsupportive marrow microenvironment and inadequate hematopoietic substrate availability. Similar pathogenic mechanisms were suspected in this horse.

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Biochemical and haematological effects of a revised dosage schedule of phenylbutazone in horses

Cited by 18 publications

References 0 publications

Clinical pharmacology and therapeutic uses of non‐steroidal anti‐inflammatory drugs in the horse

Clinical pharmacology and therapeutic uses of non‐steroidal anti‐inflammatory drugs in the horse

Phenylbutazone Pharmacokinetics and Bioavailability in the Dromedary Camel (Camelus Dromedarius)

Gelatinous Marrow Transformation and Hematopoietic Atrophy in a Miniature Horse Stallion

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