Evaluation of the safety of a combination of oral administration of phenylbutazone and firocoxib in horses.

Evaluation of the safety of a combination of oral administration of phenylbutazone and firocoxib in horses.

J Vet Pharmacol Ther. 2013 Dec 20;

Authors: Kivett L, Taintor J, Wright J

Simultaneous administration of a nonselective COX inhibitor and a COX-2 specific NSAID has not been previously reported in horses. The goal of this study was to determine the safety of a 10-day dosage regimen of phenylbutazone and firocoxib, both at their standard dosages, in horses. Six horses were administered 2.2 mg/kg of phenylbutazone and 0.1 mg/kg of firocoxib by mouth, daily for 10 days. Horses were assessed daily for changes in behavior, appetite, fecal consistency, signs of abdominal pain, and oral mucous membrane ulceration. Horses were assessed prior to and on the last day of treatment for changes in serum creatinine, albumin, total protein, and urine-specific gravity. Horses underwent endoscopic examination of the esophagus, stomach, and pylorus prior to and 24 hours after the last treatment. A significant change in serum creatinine and total protein was observed on day 10 of treatment. No other significant findings were noted during the experiment. Results indicated that co-administration of phenylbutazone and firocoxib may cause renal disease.
PMID: 24354928

The Aged Horse: Immune System and Nutrition

From the Equine Disease Quarterly, University of KY

The Importance of Nutrition in Enhancing Immunity in the Aging Horse

Over the past century, improvements in health care and advancements in biology, chemistry and medicine have extended the average lifespan of humans and companion animals, including horses. However, we are now facing new challenges with the paradox of an older population with increased longevity, while confronted with the potential for many years of poor health. A better understanding of the mechanisms leading to a decline in physiologic function with age would provide new predictive biomarkers and potential therapeutic targets.It has been well-documented that the aged, including horses, have increased susceptibility to and prolonged recovery from infectious diseases, poor responses to vaccination, and increased incidence of various cancers. Furthermore, it is now accepted that chronic inflammation (inflamm-aging) is a major underlying condition of many age-related diseases, such as atherosclerosis, arthritis, cancer, diabetes, osteoporosis, dementia, vascular diseases, obesity and metabolic syndrome.In anti-aging research, much attention is focused on nutritional interventions as practical, cost-effective approaches to mitigating this agerelated breakdown in immune function. These natural dietary compounds found in a variety of fruits, vegetables, nuts and seeds are promising candidates in helping to combat the effects of aging. They possess broad biological activities: anti-oxidative, anti-inflammatory, detoxification, regulating signaling pathway, and modulation of enzyme activities (see Table 1).Since aged horses (>20 years) have increased levels of inflammation, and treatment with longterm use of non-steroidal anti-inflammatory drugs (NSAIDs) such as flunixin meglumine and phenylbutazone can pose health problems, we are interested in nutritional interventions to counteract this inflamm-aging process.Flavonoid (quercetin) and polyphenolic compounds (curcuminoids, resveratrol, pterostilbene and hydroxypterostilbene) were compared to phenylbutazone and flunixin meglumine to determine differences in equine cytokine production in cell culture. White blood cells from aged horses were isolated and incubated overnight with each compound or NSAID at multiple concentrations. Inflammation production was measured when cells were stimulated.At varying doses (measured in micromolar units [μM]), each of the compounds and NSAIDs significantly reduced cellular inflammation: curcuminoids (20 μM), hydroxypterostilbene (40 μM), pterostilbene (80 μM), quercetin (160 μM), resveratrol (160 μM), flunixin meglumine (40 μM) and phenylbutazone (>320 μM). Interestingly, curcuminoids at a concentration of 20 μM reduced inflammation to the same level as higher doses of flunixin meglumine (40 μM) and phenylbutazone (>320 μM). All natural compounds outperformed phenylbutazone by being effective at lower doses.This preliminary research has led into two studies using aged horses to determine: 1) if a relationship exists between circulating vitamin and fatty acid levels to systemic inflammation and muscle mass, and 2) if anti-inflammatory supplementation affects immune responses to vaccination. These are preliminary steps to identify effective nutritional intervention regimens to improve function of the immune system in the aged horse.