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Summary

Flunixin meglumine and phenylbutazone are nonsteroidal anti-inflammatory drugs commonly used for the management of colic, endotoxemia, and musculoskeletal disorders in equids. Although it is not usually recommended, there appears to be an increasing trend to use nonsteroidal anti-inflammatory drugs in combination to enhance or prolong their effects. Therefore, we studied the effect of concurrent administration of flunixin (1.1 mg/kg of body weight, iv) as flunixin meglumine and phenylbutazone (2.2 mg/kg, iv) on the pharmacokinetics of each drug and on in vitro thromboxane B2 production.

Pharmacokinetic variables calculated for each drug when given alone and in combination were similar to those reported. Serum thromboxane B2 production was significantly (P = 0.05) suppressed for 12, 8, and 24 hours after administration of flunixin, phenylbutazone, and the drugs in combination, respectively. These results indicate that although concurrent administration of these drugs at the aforementioned dosages does not alter either drug disposition or clearance, it prolongs their pharmacologic effect.

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in American Journal of Veterinary Research

SUMMARY

Six mature Holstein bulls were given an 8-day course of phenylbutazone (pbz) orally (loading dose, 12 mg of pbz/kg of body weight and 7 maintenance doses of 6 mg of pbz/kg, q 24 h). Plasma concentration-vs-time data were analyzed, using nonlinear regression modeling. The harmonic mean ± pseudo-sd of the biologic half-life of pbz was 61.8 ± 12.8 hours. The arithmetic mean ± sem of the total body clearance and apparent volume of distribution were 0.0021 ± 0.0001 L/h/kg and 0.201 ± 0.009 L/kg, respectively. The predicted mean minimal plasma concentration of pbz with this dosage regimen was 75.06 ± 4.05 μg/ml.

The predicted minimal plasma drug concentration was compared with the observed minimal plasma drug concentration in another group of bulls treated with pbz for at least 60 days. Sixteen mature Holstein bulls were given approximately 6 mg of pbz/kg, po, daily for various musculoskeletal disorders. The mean observed minimal plasma concentration of pbz in the 16 bulls was 76.10 ± 2.04 μg/ ml, whereas the mean predicted minimal plasma concentration was 74.69 ± 3.10 μg/ml.

Dosages of 4 to 6 mg of pbz/kg, q 24 h, or 10 to 14 mg of pbz/kg, q 48 h, provided therapeutic plasma concentrations of pbz with minimal steady-state concentrations between 50 and 70 μg/ml.

Free access
in American Journal of Veterinary Research

SUMMARY

The pharmacokinetics of flunixin were studied in 6 adult lactating cattle after administration of single iv and im doses at 1.1 mg/kg of body weight. A crossover design was used, with route of first administration in each cow determined randomly. Plasma and milk concentrations of total flunixin were determined by use of high-pressure liquid chromatography, using an assay with a lower limit of detection of 50 ng of flunixin/ml.

The pharmacokinetics of flunixin were best described by a 2-compartment, open model. After iv administration, mean plasma flunixin concentrations rapidly decreased from initial concentrations of > 10 μg/ml to nondetectable concentrations at 12 hours after administration. The distribution phase was short (t½α, harmonic mean = 0.16 hours) and the elimination phase was more prolonged (t½β, harmonic mean = 3.14 hours). Mean ± sd clearance after iv administration was 2.51 ± 0.96 ml/kg/min. After im administration, the harmonic mean for the elimination phase (t½β) was prolonged at 5.20 hours. Bioavailability after im dosing gave a mean ± sd (n = 5) of 76.0 ± 28.0%.

Adult, lactating cows (n = 6) were challenge inoculated with endotoxin as a model of acute coliform mastitis. After multiple administration (total of 7 doses; first iv, remainder im) of 1.1 mg/kg doses of flunixin at 8-hour intervals, plasma flunixin concentrations were approximately 1 μg/ml at 2 hours after each dosing and 0.5 μg/ml just prior to each dosing. Flunixin was not detected in milk at any sampling during the study.

Flunixin concentrations necessary to induce therapeutic effects in cattle are unknown. Results of our study indicate that administration of 1.1 mg/kg doses of flunixin meglumine at 8-hour intervals would produce plasma concentrations similar to those demonstrated to be effective clinically in treatment of equine musculoskeletal disorders and colic.

Free access
in American Journal of Veterinary Research

prior to clinical use of a drug. Meloxicam is an enolic acid NSAID of the oxicam group 3 and is approved for use in dogs in Europe, Canada, and the United States. In small animals, meloxicam is used for the treatment of musculoskeletal injuries, 5

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in American Journal of Veterinary Research

Horses of all types of breeds and uses are susceptible to musculoskeletal diseases that result in lameness. Of all reported conditions, lameness ranks as one of the most common causes for poor performance in horses used for racing. 1

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in American Journal of Veterinary Research

robenacoxib have been determined in cats with kaolin-induced acute paw inflammation and acute musculoskeletal disorders and in cats undergoing surgery. 1–3 The safety after oral administration of robenacoxib to healthy cats has been reported, with

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in American Journal of Veterinary Research

reduce signs of pain and inflammation in animals with musculoskeletal disease and after surgery. 1,2 Additionally, NSAIDs can be used in conjunction with other analgesic drugs (eg, opioids) for multimodal analgesia. 3,4 Meloxicam is a commonly used

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in American Journal of Veterinary Research

NSAIDs. 1 These drugs work centrally and peripherally to prevent pain and have analgesic and anti-inflammatory effects. 2,3 They are used to prevent and treat postoperative pain, most often associated with musculoskeletal disease. 4–7 Results of

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in American Journal of Veterinary Research

. Am J Vet Res 2004 ; 65 : 350 – 356 . 10.2460/ajvr.2004.65.350 14 Bertone AL Tremaine WH Macoris DG , Effect of long-term administration of an injectable enrofloxacin solution on physical and musculoskeletal variables in adult horses . J

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in American Journal of Veterinary Research

horses for the treatment of various conditions, including colic and musculoskeletal problems, research is warranted into drugs that can mitigate these deleterious adverse effects. Misoprostol, a synthetic, stable methyl ester analog of prostaglandin E 1

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in American Journal of Veterinary Research