Date of Award

1994

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

First Advisor

Steven G. Kamerling

Abstract

The analgesic and anti-inflammatory effects of the nonsteroidal anti-inflammatory drugs (NSAIDs) ketoprofen (2.2 and 3.63 mg/kg) and phenylbutazone (4.4 mg/kg) were compared in equine models of acute synovitis and chronic hoof pain. The eicosanoids, prostaglandin E$\sb2$ (PGE$\sb2$) and leukotriene B$\sb4$ (LTB$\sb4$), increased dramatically in synovial fluid after carrageenan-induced synovitis of the intercarpal joint. PGE$\sb2$ concentrations in untreated horses peaked at 9 hours while LTB$\sb4$ concentrations peaked in all horses at 3 hours. Synovial fluid concentrations of both eicosanoids returned to near baseline by 48 hours. Lameness, joint temperature, and synovial fluid volume, protein and nucleated cells increased at 3 to 12 hours with reduction to near baseline levels by 48 hours. NSAIDs when given intravenously decreased joint concentrations of PGE$\sb2$, but LTB$\sb4$ levels were unaffected by drug administration. Both drugs decreased the signs of inflammation and lameness, but phenylbutazone was more effective. These data suggest that leukotrienes are involved in equine synovitis and the development of specific leukotriene inhibitors may be of therapeutic value. The plasma half-life of ketoprofen (2.2 mg/kg) in normal horses (0.88 hours) was higher than horses with synovitis (0.55 hours). Synovial fluid levels of ketoprofen in horses with synovitis were 6.5 times higher than normal horses at one hour. The area under the synovial fluid concentration curve for horses with synovitis was greater than in normal horses. These data suggest that the inflamed joint may serve as a site of sequestration for ketoprofen. Digital vein eicosanoid levels from horses with hoof pain from chronic laminitis were not different than those in normal horses. Although hoof pain and lameness could not be attributed to eicosanoids, both effects were reduced by the systemic administration of NSAIDs. Ketoprofen at a dose of 3.63 mg/kg (phenylbutazone equimolar dose) reduced hoof pain and lameness to a greater extent than the 2.2 mg/kg dose and phenylbutazone. These effects were still present at 24 hours for 3 of the 4 measures of hoof pain. These data suggest that phenylbutazone was more potent in alleviating acute joint inflammation whereas ketoprofen at a dosage rate of 1.65 times the therapeutic dose was more potent in alleviating chronic pain and lameness in horses.

Pages

277

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