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Topic:NSAID
Non-steroidal anti-inflammatory drugs (NSAIDs) are a class of medications commonly used in horses to manage pain and inflammation. These drugs work by inhibiting enzymes involved in the inflammatory process, specifically cyclooxygenase (COX) enzymes, which play a role in the production of prostaglandins. NSAIDs are frequently administered for conditions such as musculoskeletal disorders, colic, and post-surgical pain. Common NSAIDs used in equine medicine include phenylbutazone, flunixin meglumine, and ketoprofen. While effective, the use of NSAIDs in horses requires careful management due to potential side effects, such as gastrointestinal ulceration and renal impairment. This page compiles peer-reviewed research studies and scholarly articles that explore the pharmacology, therapeutic applications, and safety considerations of NSAIDs in equine practice.
Effects of polyphenols including curcuminoids, resveratrol, quercetin, pterostilbene, and hydroxypterostilbene on lymphocyte pro-inflammatory cytokine production of senior horses in vitro. Senior horses (aged ≥ 20 years) exhibit increased chronic, low-grade inflammation systemically, termed inflamm-aging. Inflammation is associated with many afflictions common to the horse, including laminitis and osteoarthritis, which are commonly treated with the non-steroidal anti-inflammatory drugs (NSAIDs) flunixin meglumine and phenylbutazone. Although these NSAIDs are effective in treating acute inflammatory problems, long-term treatment with NSAIDs can result in negative side effects. Thus, bioactive polyphenols including curcuminoids, resveratrol, quercetin, pterostilbene, and hydroxy...
Effect of firocoxib on cyclooxygenase 2, microsomal prostaglandin E2 synthase 1, and cytosolic phospholipase A2 gene expression in equine mononuclear cells. To validate primer sets for use in reverse transcription quantitative PCR assays to measure gene expression of cytosolic phospholipase A2 (cPLA2) and microsomal prostaglandin E2 synthase 1 (mPGES1) in equine mononuclear cells and determine the effects of firocoxib, a selective cyclooxygenase 2 (COX-2) inhibitor, on COX-2, cPLA2, and mPGES1 gene expression following incubation of mononuclear cells with lipopolysaccharide (LPS). Methods: 8 healthy adult horses. Methods: Peripheral blood mononuclear cells were isolated by density gradient centrifugation and incubated at 37°C with medium alone, f...
Pharmacokinetics of ketorolac tromethamine in horses after intravenous, intramuscular, and oral single-dose administration. Nonsteroidal anti-inflammatory drugs (NSAIDs) are an integral component of equine analgesia, yet currently available NSAIDs are both limited in their analgesic efficacy and have adverse effects. The NSAID ketorolac tromethamine (KT) is widely used in humans as a potent morphine-sparing analgesic drug but has not been fully evaluated in horses. The purpose of this study was to determine the pharmacokinetic profile of KT in horses after intravenous (i.v.), intramuscular (i.m.), and oral (p.o.) administration. Nine healthy adult horses received a single 0.5-mg/kg dose of KT via each route of admi...
Does Clinical Treatment with Phenylbutazone and Meloxicam in the Pre-ovulatory Period Influence the Ovulation Rate in Mares? The presence of anovulatory haemorrhagic follicles during the oestrous cycle of mares causes financial impacts, slowing conception and increasing the number of services per pregnancy. Non-steroidal anti-inflammatory drugs (NSAIDs) such as meloxicam and phenylbutazone are used in the treatment of several disorders in mares, and these drugs can impair the formation of prostaglandins (PGs) and consequently interfere with reproductive activity. This study aimed to evaluate the effects of treatment with NSAIDs on the development of pre-ovulatory follicles in mares. In total, 11 mares were studied o...
Pharmacokinetics and bioequivalence of 2 meloxicam oral dosage formulations in healthy adult horses. Meloxicam, a non-steroidal anti-inflammatory drug, is approved for use in horses in several countries, but an equine formulation is not available in North America. However, meloxicam is being used in an extra-label manner in horses in Canada. The purpose of this study, therefore, was to assess the bioequivalence of an approved oral meloxicam suspension (Metacam 15 mg/mL for horses; Boehringer Ingelheim Vetmedica GmBH, Ingelheim, Germany) from the European Union with human meloxicam tablets (Meloxicam 15 mg tablets; TEVA Canada, Toronto, Ontario) compounded with molasses to improve palatability...
Evaluation of the efficacy of meloxicam for post-operative management of pain and inflammation in horses after orthopaedic surgery in a placebo controlled clinical field trial. The benefit of pre and post-operative administration of non-steroidal anti-inflammatory drugs for the relief of post-operative pain and control of inflammation in horses following orthopaedic surgery has not been previously investigated in controlled clinical field trials, and the utility of such treatment is a matter of ongoing dispute. Recently the utility of post-operative pain management was emphasized. It was therefore our aim to determine the efficacy of meloxicam in horses following partial resection of fractured splint bones. This condition was selected since the limited extent of the ...
The effect of metamizole and tolfenamic acid on canine and equine adipose-derived mesenchymal stem cells (ASCs) an in vitro research. The influences of NSAIDs (Nonsteroidal Anti-inflammatory Drugs)--non-selective metamizole and selectively-acting tolfenamic acid were estimated on morphology, ultrastructure, and cytophysiological activity of canine (Ca) and equine (Eq) adipose-derived mesenchymal stem cells (ASCs). The lowest concentration of metamizole (0.01 mg/mL) stimulated the viability and cytophysiological activity of Ca ASCs and did not affect cell morphology. Stimulated cells possessed a proper, fibroblastic shape, with large, eccentrically located nuclei. Similar effects to those observed in Ca ASCs were found in Eq ...
Effect of flunixin meglumine and firocoxib on ex vivo cyclooxygenase activity in horses undergoing elective surgery. To evaluate ex vivo cyclooxygenase (COX) inhibition and compare in vitro and ex vivo COX-1 inhibition by flunixin meglumine and firocoxib in horses. Methods: 4 healthy horses for in vitro experiments and 12 healthy horses (6 males and 6 females; 5 Thoroughbreds, 5 Warmbloods, and 2 ponies) undergoing elective surgery for ex vivo experiments. Methods: 12 horses received flunixin meglumine (1.1 mg/kg, IV, q 12 h) or firocoxib (0.09 mg/kg, IV, q 24 h). Blood samples were collected before (baseline) and 2 and 24 hours after NSAID administration. Prostanoids (thromboxane B2, prostaglandin E2, and p...
Identifying behavioural differences in working donkeys in response to analgesic administration. To identify pain-related behaviour in working donkeys in order to assist their owners and veterinarians to recognise and manage pain. Objective: To identify general and specific behaviours associated with pain or its relief using a trial with the nonsteroidal anti-inflammatory drug meloxicam (Metacam). Methods: Observer-blinded, placebo-controlled trial. Methods: Forty adult male working donkeys with common clinical abnormalities were randomly assigned to receive either a single loading dose of meloxicam (1.2 mg/kg bwt per os; n = 20) or a placebo (30 mg honey/250 ml water per os; n = 20...
The use of nonsteroidal anti-inflammatory drugs in critically ill horses. To review the physiology of the cyclooxygenase (COX) enzymes with reference to the beneficial effects of nonsteroidal anti-inflammatory drugs (NSAIDs) related to their analgesic and antiendotoxic properties as well as the mechanisms responsible for adverse gastrointestinal, renal, and coagulation effects. Methods: Human and veterinary peer reviewed literature Results: NSAIDs are frequently administered to critically ill horses for their analgesic and anti-inflammatory effects. However, NSAIDs have significant side effects principally on the gastrointestinal mucosa and kidneys. These side effec...
Pharmacokinetics and pharmacodynamics of three formulations of firocoxib in healthy horses. The objectives of this study were to compare the pharmacokinetics and COX selectivity of three commercially available formulations of firocoxib in the horse. Six healthy adult horses were administered a single dose of 57 mg intravenous, oral paste or oral tablet firocoxib in a three-way, randomized, crossover design. Blood was collected at predetermined times for PGE2 and TXB2 concentrations, as well as plasma drug concentrations. Similar to other reports, firocoxib exhibited a long elimination half-life (31.07 ± 10.64 h), a large volume of distribution (1.81 ± 0.59L/kg), and a slow clearanc...
Use of firocoxib for the treatment of equine osteoarthritis. This review presents the pathogenesis and medical treatment of equine osteoarthritis (OA), focusing on firocoxib. Inhibition of prostaglandin E remains a fundamental treatment for decreasing clinical symptoms (ie, pain and lameness) associated with OA in horses. Nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit the production of prostaglandin E from the arachidonic acid pathway, continue to be a mainstay for the clinical treatment of OA. Firocoxib is a cyclooxygenase (COX)-2-preferential NSAID that has been shown to be safe and to have a 70% oral bioavailability in the horse. Three ...
Selective and simultaneous determination of NSAIDs in equine plasma by HPLC with molecularly imprinted solid-phase extraction. Detection of nonsteroidal anti-inflammatory drugs (NSAIDs) in equine plasma is a significant analytical problem in veterinary anti-doping controls. Results: A new HPLC method coupled to selective extraction with molecularly imprinted polymers was developed for the simultaneous determination in equine plasma of the NSAIDs phenylbutazone, flunixin, oxyphenbutazone, ketoprofen and naproxen. The analytical performances of the method have been evaluated both in standard solutions and equine plasma samples. Recovery: Molecularly imprinted polymers solid-phase extraction for all NSAIDs was >94% wi...
Orally administered phenylbutazone causes oxidative stress in the equine gastric mucosa. Phenylbutazone (PBZ) is widely used in equine medicine, and its side effects on the gastrointestinal tract are well known. The inhibition of prostaglandins and the oxidative stress induced by nonsteroidal anti-inflammatory drugs (NSAIDs) are described as mechanisms of gastric mucosal injury in humans. In horses, only the secondary effect of changes in cyclooxygenases is related to gastric mucosal injury. The objective of this study was to evaluate the effect of PBZ on certain antioxidative/oxidative parameters of the gastric mucosa. The concentrations of antioxidants and oxidants (superoxide d...
Prospective survey of veterinary practitioners’ primary assessment of equine colic: clinical features, diagnoses, and treatment of 120 cases of large colon impaction. Large colon impactions are a common cause of colic in the horse. There are no scientific reports on the clinical presentation, diagnostic tests and treatments used in first opinion practice for large colon impaction cases. The aim of this study was to describe the presentation, diagnostic approach and treatment at the primary assessment of horses with large colon impactions. Methods: Data were collected prospectively from veterinary practitioners on the primary assessment of equine colic cases over a 12 month period. Inclusion criteria were a diagnosis of primary large colon impaction and posi...
Effects of meloxicam and phenylbutazone on renal responses to furosemide, dobutamine, and exercise in horses. To compare the effects of 2 NSAIDs (phenylbutazone and meloxicam) on renal function in horses. Methods: 9 Thoroughbred or Standardbred mares (mean ± SD age, 5.22 ± 1.09 years [range, 2 to 12 years]; mean body weight, 470 ± 25 kg [range, 442 to 510 kg]). Methods: A randomized blinded placebo-controlled crossover study was conducted to examine the effects of treatment with phenylbutazone, meloxicam, or a placebo (control solution) on renal responses to the administration of furosemide, dobutamine, and exercise (15 minutes at 60% of maximum heart rate). Renal function was assessed by use of bi...
Pain control in horses: what do we really know? Currently, approaches to pain control in horses are a mixture of art and science. Recognition of overt pain behaviours, such as rolling, kicking at the abdomen, flank watching, lameness or blepharospasm, may be obvious; subtle signs of pain can include changes in facial expression or head position, location in the stall and response to palpation or human interaction. Nonsteroidal anti-inflammatory drugs (i.e. phenylbutazone, flunixin meglumine and firocoxib), opioids (i.e. butorphanol, morphine and buprenorphine) and α2 -adrenergic agonists (i.e. xylazine, detomidine, romifidine and medetomid...
In vivo effects of phenylbutazone on inflammation and cartilage-derived biomarkers in equine joints with acute synovitis. Although phenylbutazone (PBZ) is commonly used in equine orthopaedic practice, little is known about its in vivo effects on joint inflammation and cartilage turnover. This study investigates the effects of PBZ on inflammatory parameters, matrix metalloproteinase (MMP) activity and cartilage biomarkers in equine joints with acute synovitis. In a two-period cross-over study, transient synovitis was induced at T = 0 h in the middle carpal joint of seven ponies by lipopolysaccharide (LPS) injection. Ponies received PBZ (2 mg/kg PO twice daily) or placebo for 1 week, starting at T = 2 h. Ar...
Comparison of flunixin meglumine and meloxicam for post operative management of horses with strangulating small intestinal lesions. Ex vivo evidence suggests that cyclo-oxygenase (COX) 2-preferential inhibitor nonsteroidal anti-inflammatory drugs (NSAIDs), such as meloxicam, have a less detrimental effect on intestinal healing than flunixin meglumine (FM). Whether this translates to a beneficial effect in horses with naturally occurring strangulating small intestinal (SSI) lesions is unknown. Objective: To compare the clinical outcome of horses with naturally occurring SSI lesions treated with meloxicam or FM. Methods: Randomised prospective study. Methods: Cases presenting to the Royal Veterinary College Equine Referral H...
Nonthyroidal illness syndrome in adult horses. This study was performed to determine whether sick horses have thyroid hormone (TH) alterations similar to those observed in nonthyroidal illness syndrome in other species. Objective: Horses suffering from systemic diseases have decreased THs and inappropriately low thyroid-stimulating hormone (TSH). Methods: Seventy-one clinically normal horses; 380 hospitalized horses. Methods: Total thyroxine (TT4), free thyroxine by equilibrium dialysis (fT4D), total triiodothyronine (TT3), free triiodothyronine (fT3), and TSH were measured in normal and hospitalized horses. Disease severity was categorize...
Carprofen inhibits the release of matrix metalloproteinases 1, 3, and 13 in the secretome of an explant model of articular cartilage stimulated with interleukin 1β. Arthritic diseases are characterized by the degradation of collagenous and noncollagenous extracellular matrix (ECM) components in articular cartilage. The increased expression and activity of matrix metalloproteinases (MMPs) is partly responsible for cartilage degradation. This study used proteomics to identify inflammatory proteins and catabolic enzymes released in a serum-free explant model of articular cartilage stimulated with the pro-inflammatory cytokine interleukin 1β (IL-1β). Western blotting was used to quantify the release of selected proteins in the presence or absence of the cyc...
Evaluation of the safety of a combination of oral administration of phenylbutazone and firocoxib in horses. 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 treatm...
Naproxen in the horse: pharmacokinetics and side effects in the elderly. It is well-known that old animals show physiologic and/or pathologic variation that could modify the pharmacokinetics of drugs and the related pharmacodynamic response. In order to define the most appropriate therapeutic protocol in old horses, pharmacokinetic profile and safety of naproxen were investigated in horses aged over 18 years after oral administration for 5 days at the dose of 10 mg/kg b.w./day. After the first administration, the maximum concentration (Cmax 44.21 ± 9.21 μg/mL) was reached at 2.5 ± 0.58 h post-treatment, the harmonic mean terminal half-life was 6.96 ± 1.73 h, AU...
Efficacy of intramuscular meperidine hydrochloride versus placebo in experimental foot lameness in horses. There are no peer reviewed, blinded controlled studies regarding the skeletal analgesic efficacy of intramuscularly administered meperidine in horses. Objective: Using an adjustable heart bar shoe model of equine foot pain, the objective of this study was to test the hypothesis that meperidine (pethidine) administered intramuscularly would prove more efficacious in alleviating lameness than a saline placebo. Methods: Crossover pharmacodynamic experiment. Methods: Eight healthy adult Thoroughbred horses randomly underwent weekly i.m. treatments 1 h after lameness induction: saline placebo (1â...
Equine deep stromal abscesses (51 cases – 2004-2009)–Part 1: the clinical aspects with attention to the duration of the corneal disease, treatment history, clinical appearance, and microbiology results. To study the equine deep stromal abscesses (DSA) with focus on the duration of the corneal disease, medical treatment, season of presentation, clinical appearance, and the degree of corneal vascularization. Methods: Equine DSA diagnosed, biopsied, and surgically treated at the University of Florida Veterinary Medical Center (UFVMC) from 2004 to 2009 were identified. The medical record, clinical photographic images, and microbiology results for each case were evaluated. Frequency and prevalence calculation as well as qualitative data analysis was performed for clinical and microbiological data....
Disposition of firocoxib in equine plasma after an oral loading dose and a multiple dose regimen. The objective of this study was to determine if a single loading dose (LD), 3× the label dose of firocoxib oral paste, followed by nine maintenance doses at the current label dose achieves and maintains near steady state concentrations. Six healthy, adult mares were administered 0.3mg/kg of firocoxib on Day 0, and 0.1 mg/kg 24 h later on Day 1, and at 24 h intervals from Day 2 to Day 9, for a total of 10 doses. Blood samples were collected throughout the study. The mean firocoxib maximum plasma concentration and standard deviation was 199±97 ng/mL, 175±44 ng/mL and 183±50 ng/mL after the L...
Quantification of several acidic drugs in equine serum using LC-MS-MS. The use of nonsteroidal antiinflammatory drugs in racehorses is allowed under most jurisdictions. Furosemide is administered to treat exercise-induced pulmonary hemorrhage. To help distinguish between therapeutic and illegal uses, racing regulatory bodies have set thresholds in serum for several drugs. The method for the simultaneous detection and quantification of furosemide, flunixin, ketoprofen, phenylbutazone and oxyphenbutazone using 500 µL of serum, and liquid extraction using diethyl ether : hexanes : dichloromethane followed by liquid chromatography tandem mass spectrometry quantitati...
Phase I dose escalation of doxorubicin chemotherapy in tumor-bearing equidae. There is no information on the use of doxorubicin in horses with tumors. Objective: To determine dose-limiting toxicosis (DLT) and maximum tolerated dose (MTD) of doxorubicin in tumor-bearing horses. Methods: Seventeen horses with 34 localized or multicentric advanced tumors. Methods: Two-stage dose-ranging design involving intrapatient and interpatient dose escalation. Treatment protocol included 6 treatment cycles given at 3-week intervals with dosages ranging from 40 to 85 mg/m(2). Clinical signs, hematologic, and nonhematologic changes were evaluated. Results: Total doses ranged from 1,127...
Efficacy of cyclo-oxygenase inhibition by two commercially available firocoxib products in horses. Two firocoxib preparations for oral use are approved for use in animals in many countries: a chewable canine tablet and an equine paste. In order to reduce costs, many veterinarians use the canine product in horses even though this is an off-label use of the preparation. Objective: To determine the relative efficacy of 2 commercially available firocoxib products to inhibit prostaglandin Eâ‚‚ (PGE2) synthesis after oral dosing in horses. Methods: A crossover design using 8 adult horses (n = 4 for each preparation during each treatment period). Body weight range 532-614 kg. Methods: Horses recei...
Pharmacokinetics, pharmacodynamics, metabolism, toxicology and residues of phenylbutazone in humans and horses. The presence of horse meat in food products destined for human consumption and labelled as beef has raised several concerns of public interest. This review deals solely with one aspect of these concerns; samples of equine tissue from horses destined for the human food chain have tested positive for the non-steroidal anti-inflammatory drug, phenylbutazone. The safety of some or all such foods for human consumers is a major concern, because it was shown many years ago that phenylbutazone therapy in humans can be associated with life threatening blood dyscrasias. As an initial basis for assessing...
