Adverse effects of indomethacin in the horse

Roberts, Matthew C.

doi:10.1111/j.1365-2885.1982.tb00501.x

Cited by 12 publications

(15 citation statements)

References 6 publications

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“…This may be due 365 Pharmacokinetics of Indomethacin in Sheep to the low plasma levels of indomethacin. Similar effects have been previously reported in humans and horses (Roberts, 1982).…”

Section: Discussionsupporting

confidence: 90%

Pharmacokinetics of Indomethacin after Intraruminal Administration to Sheep

Vinagre

Encinas

Ballesteros

et al. 1999

Journal of Veterinary Medicine Series A

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The pharmacokinetics of indomethacin (7 mg/kg) was determined in six adult sheep after intraruminal administration. The plasma concentration–time curves showed different patterns for each sheep, depending on the physiological state of the gastrointestinal tract, where absorption took place, and possible enterohepatic and saliva recycling. Indomethacin was irregularly and poorly absorbed from the rumen after intraruminal administration to sheep. Plasma concentrations barely rose to the lower therapeutic margin and mean bioavailability was 38.25 ± 15.98 %. The elimination phase was slow (β = 0.015 ± 0.010 h–1) and the half‐life was long (t1/2β = 56.52 ± 31.21 h). The mean residence time was 20.01 ± 6.92 h.

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“…This may be due 365 Pharmacokinetics of Indomethacin in Sheep to the low plasma levels of indomethacin. Similar effects have been previously reported in humans and horses (Roberts, 1982).…”

Section: Discussionsupporting

confidence: 90%

Pharmacokinetics of Indomethacin after Intraruminal Administration to Sheep

Vinagre

Encinas

Ballesteros

et al. 1999

Journal of Veterinary Medicine Series A

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“…This was related to the secondary effects observed in the sheep during the first 30 min after administration, and is in agreement with reports in humans by Hasan et al . (1994) and horses (Roberts, 1982) when drug concentrations were higher than 5–6 μg/mL.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of indomethacin in sheep after intravenous and intramuscular administration

Vinagre

Rodríguez

Andrés

et al. 1998

Vet Pharm & Therapeutics

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The pharmacokinetics of indomethacin (1 mg/kg) was determined in six adult sheep after intravenous (i.v.) and intramuscular (i.m.) injection. Plasma concentrations were maintained within the therapeutic range (0.3-3.0 microg/mL) from 5 to 50 min after i.v. and from 5 to 60-90 min after i.m. administration. After two trials, indomethacin best fitted an open two-compartment model. The mean (+/- SD) volumes of distribution at steady state (Vd(ss)) were 4.10 +/- 1.40 and 4.21 +/- 1.93 L/kg and the mean clearance values (ClB) were 0.17 +/- 0.06 and 0.22 +/- 0.12 L/h x kg for i.v. and i.m. routes, respectively. The elimination phase half-lives did not show any significant difference between routes of injection (t1/2beta = 17.4 +/- 4.6 and 21.25 +/- 4.44 h, i.v. and i.m. respectively). After i.m. administration, plasma maximum concentration (Cmax = 1.10 +/- 0.68 microg/mL) was reached 10 min after dosing; the absorption phase was fast (Kab = 26 +/- 18 h(-1)) and short (t1/2ab = 2.33 +/- 1.51 min) and the mean bioavailability was 91.0 +/- 32.8%, although there was considerable interanimal variation. In some individuals, bioavailability was higher than 100%. This fact combined with the slower elimination phase after i.m. than after i.v. administration, could be related with enterohepatic recycling.

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“…Not only had it been used extensively for some 30 years but individual horses were often prescribed low dose continuous medication (2.2 to 5.0 mg/kg bodyweight [bwt]/day) for periods of several months (Scott Dunn 1971;Gabel, Tobin, Ray and Maylin 1977). Also, although there had been a few reports in the literature of suspected toxicity, including low haematocrit (Roberts 1982), hypoplastic anaemia (Dunavant and Murray 1975), colic, epistaxis and intestinal ulceration (Gabriel and Martin 1962;Hopes 1972) and necrotising phlebitis of portal venules (Gabriel and Martin 1962), it was by no means clear that phenylbutazone was implicated in all of these reactions. The relatively short halflife of phenylbutazone in the horse compared with man led to the assumption that once or twice daily therapy would be unlikely to lead to cumulation of the drug in the body to toxic levels.…”

Section: Phenylbutazonementioning

confidence: 99%

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

Lees

Higgins

1985

Equine Veterinary Journal

143

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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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Adverse effects of indomethacin in the horse

Cited by 12 publications

References 6 publications

Pharmacokinetics of Indomethacin after Intraruminal Administration to Sheep

Pharmacokinetics of Indomethacin after Intraruminal Administration to Sheep

Pharmacokinetics of indomethacin in sheep after intravenous and intramuscular administration

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

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