Phenylbutazone is a non-steroidal anti-inflammatory drug (NSAID) commonly used in horses to manage pain and inflammation associated with musculoskeletal disorders. It functions by inhibiting the cyclooxygenase enzymes (COX-1 and COX-2), which play a role in the inflammatory process. Phenylbutazone is administered in various formulations, including oral and injectable forms, and is often used in the treatment of conditions such as arthritis, laminitis, and soft tissue injuries. The pharmacokinetics, therapeutic effects, and potential side effects, such as gastrointestinal irritation and renal impairment, are subjects of ongoing research. This page compiles peer-reviewed research studies and scholarly articles that explore the pharmacology, clinical applications, and safety considerations of phenylbutazone in equine medicine.
Loncar KD, Ortis HA, Foss RR.Production of embryos via intracytoplasmic sperm injection (ICSI) is a common clinical procedure in equine practice. A recent study indicates that treatment of mares with phenylbutazone paste significantly lowers blastocyst production after ICSI of recovered oocytes. The current study was conducted to determine the effect of different methods of phenylbutazone administration on in vitro embryo production of recovered oocytes in mares. Unassigned: In study 1 (July 29 through September 18, 2024), 14 mares received either oral liquid phenylbutazone once daily for 10 days or no treatment. On the l...
Vinijkumthorn R, Prapaiwan N, Chotikaprakal T, Prompiram P, Phaonakrop N, Roytrakul S, Tesena P.Phenylbutazone (PBZ) can potentially induce gastrointestinal ulceration, and early detection of PBZ-induced gastroenteropathy will be useful for the diagnosis, treatment, and prevention of PBZ toxicity. Objective: To identify putative proteins associated with equine gastric ulcer syndrome after clinical dose (4.4 mg/kg) administration of PBZ by proteomic study. Methods: In vivo experiments. Methods: Proteomic analysis using LC-MS/MS compared protein expression in serum and faeces of seven PBZ-treated horses with seven placebo-treated controls, and a novel putative biomarker was validated via...
Kemp KL, Yuen NKY, Skinner JE, Bertin FR.Phenylbutazone is prescribed to manage pain caused by hyperinsulinemia-associated laminitis. Phenylbutazone reduces glucose and insulin concentrations in horses with insulin dysregulation (ID) but the underlying mechanism of action is unknown. Objective: Investigate the effect of phenylbutazone on tissue insulin sensitivity in horses. It is hypothesized that the reduced glucose and insulin concentrations in horses with ID receiving phenylbutazone are mediated by a higher tissue insulin sensitivity. Methods: Fifteen light breed horses, including seven with ID. Methods: Randomized cross-over stu...
Kemp KL, Skinner JE, Bertin FR.Phenylbutazone is prescribed for laminitis-associated pain and decreases glucose and insulin responses to an oral glucose test (OGT) in horses with insulin dysregulation (ID). Objective: Investigate the effect of phenylbutazone administration on the enteroinsular axis in horses. Methods: Sixteen horses, including 7 with ID. Methods: Randomized cross-over study design, with horses assigned to treatment with phenylbutazone (4.4 mg/kg IV q24h) or placebo (5 mL 0.9% saline). On Day 9 of treatment, an OGT was conducted, followed by a 10-day washout period, administration of the alternative trea...
Bishop RC, Jonk KM, Migliorisi A, Austin SM, Mullins EC, Wilkins PA.Polycythaemia and coagulopathy are identified risk factors for non-survival in critically ill horses. Assessment of coagulation is recommended for critical care monitoring but may be affected by concurrent polycythaemia. Objective: To evaluate the effects of induced polycythaemia on coagulation parameters as measured by a point-of-care viscoelastic coagulation device (VCM Vet™). Methods: Prospective interventional study. Methods: Healthy adult horses (n = 7) were given 6 mcg/kg of phenylephrine IV over 15 min to induce transient polycythaemia. Samples for packed cell volume (PCV), to...
Zaghloul IY, Bedenice D, Ceresia ML, Jones PH, Sanchez-Londono A, Lobo MN, Böhlke M, Paradis MR.To evaluate the effects of aging on phenylbutazone (PBZ) disposition in older horses (≥ 25 years old) compared to young adults (4 to 10 years old) by characterizing the pharmacokinetic profile of PBZ and its active metabolite, oxyphenbutazone (OPBZ), following a 2.2-mg/kg dose, IV. We hypothesized that the disposition of PBZ will be affected by age. Methods: 16 healthy horses (8 young adults aged 4 to 10 years and 8 geriatric horses ≥ 25 years old). Methods: Horses were administered a single 2.2-mg/kg PBZ dose, IV. Plasma samples were collected at designated time points and frozen at -80 Â...
Tesena P, Vinijkumthorn R, Preuksathaporn T, Piyakul P, Chotikaprakal T, Sirireugwipas R, Wong-Aree K, Prapaiwan N.Phenylbutazone (PBZ) is a widely used nonsteroidal anti-inflammatory drug for horses. However, because of its gastrointestinal side effects, its administration requires careful attention in veterinary practice. Malondialdehyde (MDA) is a serum biomarker associated with increased damage to the equine gastrointestinal system. This study investigated the hematological effects and alterations in the gastrointestinal tract and assessed serum MDA concentrations following repeated oral PBZ administration at clinical doses. Fourteen horses were randomly divided into control and treatment groups. All h...
Whitfield-Cargile CM, Chung HC, Coleman MC, Cohen ND, Chamoun-Emanuelli AM, Ivanov I, Goldsby JS, Davidson LA, Gaynanova I, Ni Y, Chapkin RS.The equine gastrointestinal (GI) microbiome has been described in the context of various diseases. The observed changes, however, have not been linked to host function and therefore it remains unclear how specific changes in the microbiome alter cellular and molecular pathways within the GI tract. Further, non-invasive techniques to examine the host gene expression profile of the GI mucosa have been described in horses but not evaluated in response to interventions. Therefore, the objectives of our study were to (1) profile gene expression and metabolomic changes in an equine model of non-ster...
Xue C, Segabinazzi L, Hall A, Dzikiti TB, French H, Gilbert R.Clinically, flunixin meglumine (FM) and phenylbutazone (PBZ) are preferentially selected for the treatment of visceral and musculoskeletal pain, respectively, in horses. In donkeys, there is no information to support or refute this conventional conjecture. Objective: To compare postoperative outcomes in a group of jennies treated with intravenous FM or oral PBZ. Methods: Fourteen jennies unilaterally ovariectomised by standing left flank laparotomy. Methods: Retrospective cohort study. Methods: Data from medical records of ovariectomised jennies (case details, weight, non-steroidal anti-inflam...
Kemp KL, Skinner JE, Bertin FR.Phenylbutazone is often prescribed to manage pain caused by hyperinsulinemia-associated laminitis, but in diabetic people nonsteroidal anti-inflammatory drugs increase insulin secretion and pancreatic activity. Objective: Investigate the effect of phenylbutazone administration on insulin secretion in horses. It was hypothesized that phenylbutazone will increase insulin secretion in horses with insulin dysregulation (ID). Methods: Sixteen light breed horses, including 7 with ID. Methods: Randomized cross-over study design. Horses underwent an oral glucose test (OGT) after 9 days of treatment ...
Brown KA, Gregorio EN, Barot D, Usimaki A, Linardi RL, Missanelli JR, You Y, Robinson MA, Ortved KF.To determine the effects of a single dose of the NSAIDs phenylbutazone, firocoxib, flunixin meglumine, and ketoprofen on concentrations of growth factors and cytokines in autologous protein solution (APS) and platelet-rich plasma (PRP). Methods: 6 adult university-owned horses. Methods: For the first phase, 6 horses were randomized to receive ketoprofen (1,000 mg) or flunixin meglumine (500 mg) IV. Blood was obtained and processed for APS (Pro-Stride) and PRP (Restigen) before and 6 hours after administration of NSAIDs. Horses underwent a 2-week washout period, after which the protocol was rep...
Interlandi C, Tabbì M, Di Pietro S, D'Angelo F, Costa GL, Arfuso F, Giudice E, Licata P, Macrì D, Crupi R, Gugliandolo E.The aim of this study was to evaluate the effect of oral cannabidiol (CBD) administration in addition to a conventional analgesic protocol on the clinical signs of 20 horses with mild joint osteoarthritis. The horses were randomly assigned to either the control group (C group) or the cannabidiol group (CBD group). Both groups were treated with phenylbutazone for 5 days. The CBD group received 0.03 mg/kg cannabidiol in hemp oil orally once daily for 14 days in addition to phenylbutazone treatment. All subjects were monitored for clinical parameters, oxidative status and blood counts. Pain...
Citarella G, Heitzmann V, Ranninger E, Bettschart-Wolfensberger R.This systematic review aimed to identify the evidence concerning the analgesic efficacy of non-steroidal anti-inflammatory drugs to treat abdominal pain in horses, and to establish whether one non-steroidal anti-inflammatory drug could provide better analgesia compared to others. This systematic review was conducted following the "Systematic Review Protocol for Animal Intervention Studies". Research published between 1985 and the end of May 2023 was searched, using three databases, namely, PubMed, Embase, and Scopus, using the words equine OR horse AND colic OR abdominal pain AND non-steroidal...
White JM, Colbath AC, Schott HC.Treatment with phenylbutazone (nonselective COX inhibitor) decreases the diuretic and natriuretic effects of furosemide by nearly 30% but the effects of COX-2 specific inhibitors (firocoxib) and atypical NSAIDs (dipyrone) are unknown. Objective: Furosemide-induced diuresis after pretreatment with firocoxib or dipyrone is diminished to a lesser extent than after pretreatment with phenylbutazone. Methods: Eight healthy mares. Methods: Each mare received 4 treatments in a prospective experimental crossover study using a replicated 4 × 4 Latin Square design: furosemide alone (FU), furosemide an...
Vinijkumthorn R, Bauck AG, Vidyasagar S, Freeman DE.Right dorsal colitis causes chronic colic associated with long-term treatment with nonsteroidal antiinflammatory drugs (NSAIDs). This study was designed to determine if NSAIDs could inhibit anion transporters that protect against intestinal mucosal injury in other species. Methods: 20 healthy horses. Methods: The effects of indomethacin (INDO) and firocoxib (FIR), on short-circuit current (Isc) in mucosa from the right dorsal colon (RDC) and right ventral colon (RVC) were measured in Ussing chambers by standard electrophysiological techniques. Immunohistochemical methods were used to detect ap...
O'Brien M, Mochel JP, Kersh K, Wang C, Troy J.Pain management is critical to equine welfare with non-steroidal anti-inflammatory drugs (NSAID) commonly used in horses. However, systemic NSAID use is limited by harmful gastrointestinal and renal side effects. Intravenous regional limb perfusion (IVRLP) is a technique used in horses that produces high, local antibiotic concentrations while limiting systemic circulation. NSAID-IVRLP would be a novel method of local pain management while limiting systemic NSAID side effects. To date, NSAID-IVRLP administration has not been reported in horses. This study aimed to identify the pharmacokinetics ...
Costa LRR, Swiderski C, Palm C, Aleman M.To investigate if hepatitis A virus cell receptor 1/kidney injury molecule 1 (HAVCR1/KIM1) in urine is detectable concurrently with increases in serum creatinine concentrations in horses receiving a recommended dose of phenylbutazone (PBZ) for 7Â days. Methods: Preliminary study. Methods: Ten clinically healthy horses with normal physical examination and laboratory work were randomly assigned to PBZ or placebo groups (5 each). The PBZ group received PBZ at 4.4Â mg/kg mixed with corn syrup orally every 12Â hours. The placebo group received corn syrup orally every 12Â hours. Both groups were tre...
Li Z, Du S, Wang X, Zhang L, Liu X, Fan Q, Yang H, Gao R.Phenylbutazone (PBZ) is the most commonly used drug to treat symptoms of lameness in horses; however, it is associated with adverse effects such as gastric ulcer syndrome (EGUS). Interestingly, many practitioners prescribe omeprazole (OME) concurrently with PBZ to prevent the development of EGUS. However, the efficacy and safety of this practice in Mongolian horses with chronic lameness remain unknown. Objective: To evaluate the clinical effects of a combination of PBZ and OME on chronic lameness in Mongolian horses. Methods: Randomised block experimental design. Methods: Eighteen Mongolian ho...
Taguchi T, Morales Yniguez FJ, Takawira C, Andrews FM, Lopez MJ.Osteoarthritis (OA) accounts for up to 60% of equine lameness. Agmatine, a decarboxylated arginine, may be a viable option for OA management, based on reports of its analgesic properties. Six adult thoroughbred horses, with lameness attributable to thoracic limb OA, received either daily oral phenylbutazone (6.6 mg/kg), agmatine sulfate (25 mg/kg) or a control for 30 days, with 21-day washout periods between treatments. Subjective lameness, thoracic limb ground reaction forces (GRF), plasma agmatine and agmatine metabolite levels were evaluated using an established rubric, a force platform, an...
Flood J, Stewart AJ.Effective pain management in horses can be a challenge despite the understanding that appropriate analgesia improves animal welfare and increases treatment success. The administration of NSAID drugs, particularly phenylbutazone and flunixin, are common practice in equine veterinary patients. Known for their analgesic and anti-inflammatory properties, NSAIDs are used for the treatment of a variety of conditions in horses, from gastrointestinal to orthopedic pain. Despite extensive usage, NSAIDs have a narrow margin of safety and the body of literature documenting the efficacy and side effects o...
Ahmadnejad M, Jalilzadeh-Amin G, Sykes BW.Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), like phenylbutazone (PBZ), are prescribed to treat pain and inflammation in the equine. However, experimentally their use has been associated with the development of Equine Glandular Gastric Disease (EGGD). To evaluate the prophylactic effects of Glycyrrhiza glabra root extracts (GGRE) on EGGD induction following oral administration of PBZ, 12 donkeys were used. Animals were divided into three equal groups (A, B and C) in a randomized block design. A: placebo, B: PBZ (4.4 mg/kg PO q 12 h) and C: PBZ plus GGRE (17.6 mg/kg PO q 24h). Gastroscopy an...
Mercer MA, McKenzie HC, Byron CR, Pleasant RS, Bogers SH, Council-Troche RM, Werre SR, Burns T, Davis JL.Acetaminophen has been used clinically in horses alone or combined with traditional non-steroidal anti-inflammatory drugs for treatment of musculoskeletal pain in horses. Objective: To determine the pharmacokinetics and efficacy of acetaminophen at two doses in horses with mechanically induced lameness compared with phenylbutazone or placebo control. Methods: In vivo experiment. Methods: Nine healthy mares with mechanical lameness induced via a reversible sole pressure horseshoe model were treated with acetaminophen (20 mg/kg PO; A20), acetaminophen (30 mg/kg PO; A30), phenylbutazone (2.2â...
Bauck AG, Vidyasagar S, Freeman DE.To examine bicarbonate (HCO3-) secretion ex vivo in the equine large colon to determine any differences between the right dorsal colon (RDC) and right ventral colon (RVC). The effect of phenylbutazone (PBZ) on HCO3- secretion was examined in the RDC. Methods: 14 healthy horses. Methods: In anesthetized horses (n = 10), segments of mucosa from RDC and RVC were harvested to measure HCO3- secretion ex vivo with the pH Stat method. The effect of PBZ on HCO3- secretion in the RDC was studied in 4 additional horses. Results: Three distinct mechanisms of HCO3- secretion previously described in a muri...
Walters B, Trumble TN, Wendt-Hornickle E, Kennedy M, Guedes A.Apoptosis is an important mechanism underlying chondrocyte loss in osteoarthritis that could be affected by modulation of lipid signaling via inhibition of cyclooxygenases (COX) and soluble epoxide hydrolase (sEH). Objective: To determine the impact of inhibiting COX and sEH alone or in combination on apoptosis of equine chondrocytes. Methods: Cultured primary equine chondrocytes were subjected to serum deprivation or incubation with 1 μg/ml tunicamycin for 24 h to induce apoptosis via caspase activation and endoplasmic reticulum (ER) stress, respectively. Cells were treated with the non-se...
Waller P, Lomnicka I, Lucas C, Johnson S, Dirikolu L.The number of publications for most common drug violations in racehorses is limited. This study reports the most common medication violations in racehorses at four major racetracks in Louisiana between 2016 and 2020. During this 5-year period, 27,237 blood samples and 25,672 urine samples collected during the course of normal race meeting activities were analysed by initial screening procedure utilizing Liquid Chromatography Mass Spectrometry (LC-MS/MS). Following initial screening, suspect samples were subject to quantitative or semi- quantitative confirmation analysis by LC-MS/MS. The total ...
Houck EL, Papich MG, Delk KW.Southern white rhinoceros (Ceratotherium simum simum) frequently develop painful conditions, such as traumatic injuries or osteoarthritis, necessitating the administration of pain-relieving medications. One of the preferred treatments is the nonsteroidal anti-inflammatory drug phenylbutazone because of the availability of oral formulations and the familiarity of its use in horses. For the main study, a single oral dose of phenylbutazone at 2 mg/kg was administered to healthy adult rhinoceros (n = 33) housed at six North American zoological institutions. Each rhinoceros had up to four blood ...
Tucker L, Trumble TN, Groschen D, Dobbs E, Baldo CF, Wendt-Hornickle E, Guedes AGP.Objective: To determine the symptomatic and disease-modifying capabilities of sEH and COX inhibitors during joint inflammation. Methods: Using a blinded, randomized, crossover experimental design, 6 adult healthy horses were injected with lipopolysaccharide (LPS; 3 μg) from E. coli in a radiocarpal joint and concurrently received the non-selective cyclooxygenase (COX) inhibitor phenylbutazone (2 mg/kg), the sEH inhibitor t-TUCB (1 mg/kg) or both (2 mg/kg phenylbutazone and 0.1, 0.3, and 1 mg/kg t-TUCB) intravenously. There were at least 30 days washout between treatments. Joint pain (assessed...
Whitfield-Cargile CM, Coleman MC, Cohen ND, Chamoun-Emanuelli AM, DeSolis CN, Tetrault T, Sowinski R, Bradbery A, Much M.Gastrointestinal (GI) injury and dysbiosis are adverse events associated with nonsteroidal anti-inflammatory drug (NSAID) use in horses. Phenylbutazone has been shown to alter GI barrier function both in vitro and ex vivo, but its effects on barrier function have not been assessed in vivo. In addition, the ability of nutritional therapeutics to prevent these changes is not known. Objective: Our objectives were to determine whether (a) phenylbutazone affected barrier function in vivo and (b) if phenylbutazone-induced GI injury could be ameliorated by the use of a nutritional therapeutic. Method...
Siwinska N, Zak A, Paslawska U.Acute kidney injury (AKI) in horses may develop as a complication of a primary disease or following the administration of nephrotoxic drugs, and may pose a diagnostic challenge. Hence, the main objective of this study was to evaluate the concentrations and diagnostic significance of serum symmetric dimethylarginine (SDMA) and conventional renal dysfunction biomarkers in healthy horses, horses at risk of developing AKI, and horses with clinically evident AKI. A second aim was to assess how gastrointestinal disease and exposure to potentially nephrotoxic drugs affected SDMA levels. Thirty health...
Goodrich LR, Nixon AJ.The medical treatment of osteoarthritis (OA) in the horse is one of the most utilized therapeutic regimens in the equine practice. It is important to understand the anatomy of synovial joints and the pathophysiology of the disease process to treat OA adequately. Once a thorough understanding of the disease process is comprehended the proper combination of systemic nonsteroidal anti-inflammatory drugs (NSAIDs), intraarticular steroids, viscosupplementation and chondroprotectants can be used to treat the disease and inhibit further progression of degenerative changes to the cartilage surface. Th...
Higgins AJ, Lees P.Arachidonic acid is a polyunsaturated fatty acid covalently bound in esterified form in the cell membranes of most body cells. Following irritation or injury, arachidonic acid is released and oxygenated by enzyme systems leading to the formation of an important group of inflammatory mediators, the eicosanoids. It is now recognised that eicosanoid release is fundamental to the inflammatory process. For example, the prostaglandins and other prostanoids, products of the cyclooxygenase enzyme pathway, have potent inflammatory properties and prostaglandin E2 is readily detectable in equine acute in...
Beretta C, Garavaglia G, Cavalli M.We report on the inhibitory activity of the NSAIDs meloxicam, carprofen, phenylbutazone and flunixin, on blood cyclooxygenases in the horse using in vitro enzyme-linked assays. As expected, comparison of IC50 indicated that meloxicam and carprofen are more selective inhibitors of COX-2 than phenylbutazone and flunixin; meloxicam was the most advantageous for horses of four NSAIDs examined. However at IC80, phenylbutazone (+134.4%) and flunixin (+29.7%) had greater COX-2 selectivity than at IC50, and meloxicam (-41.2%) and carprofen (-12.9%) had lower COX-2 selectivity than at IC50. We therefor...
Brideau C, Van Staden C, Chan CC.To determine potency and selectivity of nonsteroidal anti-inflammatory drugs (NSAID) and cyclooxygenase- (COX-) specific inhibitors in whole blood from horses, dogs, and cats. Methods: Blood samples from 30 healthy horses, 48 healthy dogs, and 9 healthy cats. Methods: Activities of COX-1 and COX-2 were determined by measuring coagulation-induced thromboxane and lipopolysaccharide-induced prostaglandin E2 concentrations, respectively, in whole blood with and without the addition of various concentrations of phenylbutazone, flunixin meglumine, ketoprofen, diclofenac, indomethacin, meloxicam, car...
Guedes AG, Morisseau C, Sole A, Soares JH, Ulu A, Dong H, Hammock BD.A 4-year old, 500 kg Thoroughbred female horse diagnosed with bilateral forelimb laminitis and cellulitis on the left forelimb became severely painful and refractory to non-steroidal anti-inflammatory therapy (flunixin meglumine on days 1, 2, 3 and 4; and phenylbutazone on days 5, 6 and 7) alone or in combination with gabapentin (days 6 and 7). Methods: Pain scores assessed independently by three individuals with a visual analog scale (VAS; 0 = no pain and 10 = worst possible pain) were 8.5 on day 6, and it increased to 9.5 on day 7. Non-invasive blood pressure monitoring revealed severe hyper...
MacAllister CG, Morgan SJ, Borne AT, Pollet RA.The relative toxicity of phenylbutazone, flunixin meglumine, and ketoprofen was studied in healthy adult horses. Sixteen horses were randomly assigned to receive 10 ml of physiologic saline solution, or ketoprofen (2.2 mg/kg of body weight), flunixin meglumine (1.1 mg/kg), or phenylbutazone (4.4 mg/kg) IV, every 8 hours, for 12 days. Results of CBC, serum biochemical analyses, and fecal occult blood tests were monitored. On day 13, all horses were euthanatized and complete necropsy examinations were performed. Mean CBC values remained within normal limits for all groups. Phenylbutazone-treated...
Müller M, Raabe O, Addicks K, Wenisch S, Arnhold S.In equine medicine, stem cell therapies for orthopaedic diseases are routinely accompanied by application of NSAIDs (non-steroidal anti-inflammatory drugs). Thus, it has to be analysed how NSAIDs actually affect the growth and differentiation potential of MSCs (mesenchymal stem cells) in vitro in order to predict the influence of NSAIDs such as phenylbutazone, meloxicam, celecoxib and flunixin on MSCs after grafting in vivo. The effects of NSAIDs were evaluated regarding cell viability and proliferation. Additionally, the multilineage differentiation capacity and cell migration was analysed. N...
Toutain PL, Autefage A, Legrand C, Alvinerie M.The purpose of the present study was to establish in the horse the relationship between plasma concentration profiles of phenylbutazone (PBZ) and flunixin meglumine (FM) and their pharmacological effects in order to build a predictive pharmacokinetic/pharmacodynamic (PK/PD) model. In five horses, an experimental arthritis was induced by injecting Freund's adjuvant into a carpal joint. PBZ (4 mg/kg) and FM (1 mg/kg) were injected by the intravenous route as a single intravenous dose in two different trials. Five pharmacodynamic end-points were regularly measured after test article injection usi...
Sullivan KA, Hill AE, Haussler KK.Common methods used to treat back problems in horses need to be assessed objectively. Objective: To measure spinal mechanical nociceptive thresholds (MNTs) and evaluate the effects of chiropractic, massage and phenylbutazone, compared with active and inactive control groups. Methods: Baseline MNTs at 7 sites within the thoracolumbar and sacral regions were measured in 38 healthy mature horses exhibiting no clinical signs of lumbar pain. Horses were assigned to one of 3 treatment groups: instrument-assisted chiropractic treatment, therapeutic massage and phenylbutazone; or 2 control groups: rid...
Lees P, Higgins AJ.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 synthe...
Sanchez LC, Robertson SA.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...
Tung JT, Arnold CE, Alexander LH, Yuzbasiyan-Gurkan V, Venta PJ, Richardson DW, Caron JP.To determine the effects of prostaglandin E2 (PGE2) on recombinant equine interleukin (IL)-1beta-stimulated expression of matrix metalloproteinases (MMP 1, MMP 3, MMP 13) and tissue inhibitor of matrix metalloproteinase 1 (TIMP 1) in vitro. Methods: Cultured equine chondrocytes. Methods: Stationary monolayers of first-passage chondrocytes were exposed to graduated concentrations of PGE2 with or without a subsaturating dose (50 pg/ml) of recombinant equine IL-1beta (reIL-1beta) to induce expression of MMP 1, MMP 3, MMP 13, and TIMP 1, followed by RNA isolation and northern blotting. In subseque...
Interlandi C, Tabbì M, Di Pietro S, D'Angelo F, Costa GL, Arfuso F, Giudice E, Licata P, Macrì D, Crupi R, Gugliandolo E.The aim of this study was to evaluate the effect of oral cannabidiol (CBD) administration in addition to a conventional analgesic protocol on the clinical signs of 20 horses with mild joint osteoarthritis. The horses were randomly assigned to either the control group (C group) or the cannabidiol group (CBD group). Both groups were treated with phenylbutazone for 5 days. The CBD group received 0.03 mg/kg cannabidiol in hemp oil orally once daily for 14 days in addition to phenylbutazone treatment. All subjects were monitored for clinical parameters, oxidative status and blood counts. Pain...
Owens JG, Kamerling SG, Stanton SR, Keowen ML, Prescott-Mathews JS.To compare the analgesic and anti-inflammatory effects of the nonsteroidal anti-inflammatory drugs (NSAID), ketoprofen (2.20 and 3.63 mg/kg of body weight) and phenylbutazone (4.40 mg/kg), in an acute equine synovitis model. Methods: 4 groups of 6 horses received NSAID or saline solution in a randomized design. Methods: 24 clinically normal mares and geldings. Methods: Left intercarpal joints were injected with sterile carrageenan to induce synovitis at the same time as IV administration of NSAID or saline solution. Clinical assessments were made and synovial fluid was withdrawn at 0, 1, 3, 6,...
Doucet MY, Bertone AL, Hendrickson D, Hughes F, Macallister C, McClure S, Reinemeyer C, Rossier Y, Sifferman R, Vrins AA, White G, Kunkle B, Alva R....To compare efficacy and safety of paste formulations of firocoxib and phenylbutazone in horses with naturally occurring osteoarthritis. Methods: Randomized controlled clinical trial. Methods: 253 client-owned horses with naturally occurring osteoarthritis. Methods: Horses were treated with firocoxib (0.1 mg/kg [0.045 mg/lb], PO, q 24 h) or phenylbutazone (4.4 mg/kg [2 mg/lb], PO, q 24 h) for 14 days. Physical examinations and lameness evaluations were performed prior to treatment and after 7 and 14 days. Clinical improvement was defined as a reduction of at least 1 lameness grade or a combined...
de Grauw JC, van Loon JP, van de Lest CH, Brunott A, van Weeren PR.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...
Raekallio M, Taylor PM, Bennett RC.Twenty-five horses undergoing arthroscopic surgery were studied to develop a scheme for assessing pain in horses while investigating the effects of phenylbutazone (PBZ) analgesia. Fifteen of the 25 horses received PBZ 4 mg/kg intravenously (IV) before surgery and 2 mg/kg (IV) every 12 hours thereafter until 60 hours; the remaining 10 (placebo group) were given a corresponding volume of saline. In both groups, venous blood samples were collected for catecholamine, beta-endorphin, and cortisol assays before premedication and up to 72 hours after surgery. Postoperative pain was evaluated by measu...
Flood J, Stewart AJ.Effective pain management in horses can be a challenge despite the understanding that appropriate analgesia improves animal welfare and increases treatment success. The administration of NSAID drugs, particularly phenylbutazone and flunixin, are common practice in equine veterinary patients. Known for their analgesic and anti-inflammatory properties, NSAIDs are used for the treatment of a variety of conditions in horses, from gastrointestinal to orthopedic pain. Despite extensive usage, NSAIDs have a narrow margin of safety and the body of literature documenting the efficacy and side effects o...
Karcher LF, Dill SG, Anderson WI, King JM.Moderate to severe ulcerative colitis of the right dorsal colon was diagnosed by necropsy or by exploratory celiotomy and biopsy in 13 horses with a primary clinical complaint of either colic, diarrhea, or weight loss. Clinical signs varied from acute fulminating diarrhea (possibly with fever), colic, dehydration, endotoxic shock and death, to a chronic condition manifested by mild intermittent colic up to several months in duration, and weight loss with or without mild diarrhea. In a large percentage of the horses, those affected had been hypovolemic and received nonsteroidal anti-inflammator...
Lees P, Toutain PL.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...
Duz M, Marshall JF, Parkin TD.There is little knowledge of the prescription of nonsteroidal anti-inflammatory drugs (NSAIDs) and whether their prescription varies between countries. Objective: To describe prescription practices of NSAIDs in equids in the United Kingdom (UK), United States of America (USA) and Canada. Methods: Descriptive observational study. Methods: Free-text electronic medical records from 141,543 equids from 10 equine practices in the UK, 255,777 equids from 7 equine practices with 20 branches from the USA and 2 practices with 7 branches from Canada were evaluated. A validated text-mining technique was ...
Waters LJ, Hanrahan JP, Tobin JM, Finch CV, Parkes GMB, Ahmad SA, Mohammad F, Saleem M.Three mesoporous silica excipients (Syloid® silicas AL-1 FP, XDP 3050 and XDP 3150) were formulated with a model drug known for its poor aqueous solubility, namely phenylbutazone, in an attempt to enhance the extent and rate of drug dissolution. Although other forms of mesoporous silica have been investigated in previous studies, the effect of inclusion with these specific Syloid® silica based excipients and more interestingly, with phenylbutazone, is unknown. This work reports a significant enhancement for both the extent and rate of drug release for all three forms of Syloid® silica at a ...
McConnico RS, Morgan TW, Williams CC, Hubert JD, Moore RM.To determine pathophysiologic effects of phenylbutazone on the equine right dorsal colon (RDC). Methods: 12 healthy adult horses. Methods: A controlled crossover observational study was conducted. Clinical and serum variables, colonic inflammation (histologic grading), and measurement of myeloperoxidase (MPO) activity, malondialdehyde (MDA) and prostaglandin E(2) (PGE(2)) concentrations, ingesta volatile fatty acid (VFA) content, and arterial blood flow in the RDC were evaluated for a 21-day period in horses administered phenylbutazone (8.8 mg/kg, PO, q 24 h) or a control substance. Results: D...
Noble G, Edwards S, Lievaart J, Pippia J, Boston R, Raidal SL.Safety of meloxicam, a potent NSAID with selective COX-2 inhibition, has not been evaluated in horses. Objective: To evaluate pharmacokinetics and safety of single and repeated oral doses of meloxicam in adult horses. Methods: Forty-nine healthy, university-owned adult lightbreed horses. Methods: Study conducted in 2 parts. Part I addressed pharmacokinetics of single oral dose meloxicam (0.6 mg/kg) in 16 horses. Part II, 33 horses were randomly assigned to 5 treatment groups to assess prolonged administration (0.6 mg/kg PO q24h for 6 weeks, n = 7) or higher doses (1.8 mg/kg, n = 7, or 3.0 mg/k...
Whitfield-Cargile CM, Chamoun-Emanuelli AM, Cohen ND, Richardson LM, Ajami NJ, Dockery HJ.Non-steroidal anti-inflammatory drugs (NSAIDs) are routinely used in both veterinary and human medicine. Gastrointestinal injury is a frequent adverse event associated with NSAID use and evidence suggests that NSAIDs induce gastrointestinal microbial imbalance (i.e., dysbiosis) in both animals and people. It is unknown, however, whether cyclooxygenase (COX)-2-selective NSAIDs induce dysbiosis, or if this phenomenon occurs in horses administered any class of NSAIDs. Therefore, our objectives were to determine whether the composition and diversity of the fecal microbiota of adult horses were alt...
Siard MH, McMurry KE, Adams AA.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...
Collins LG, Tyler DE.In a retrospective study of 269 horses that had been treated with phenylbutazone, horses receiving less than or equal to 8.8 mg/kg of body weight/day for less than or equal to 4 days or 2 to 4 mg/kg of body weight/day for up to 50 days remained clinically normal. Anorexia, depression, colic, hypoproteinemia, diarrhea, melena, weight loss, ventral edema, petechial hemorrhages of mucous membranes, oral and gastrointestinal tract erosions and ulcers, renal papillary necrosis, and death were among the complications seen in horses that had received greater than 8.8 mg/kg of body weight/day. In 2 ca...
Tung JT, Venta PJ, Caron JP.To determine the effects of recombinant equine IL-1beta and a number of antiinflammatory compounds on the expression and activity of inducible nitric oxide synthase (iNOS) in cultured equine chondrocytes. Methods: RT-PCR methods were used to amplify a portion of the equine iNOS message to prepare an RNA probe. Northern blot analysis was used to quantify the expression of iNOS in first passage cultures of equine articular chondrocytes propagated in the presence or absence of recombinant equine interleukin-1beta (reIL-1beta), dexamethasone (DEX), polysulfated glycosaminoglycan (PSGAG), hyalurona...
Gunson DE, Soma LR.Acute renal papillary necrosis occurred in five horses given normal therapeutic doses of phenylbutazone and deprived of water for 36 to 48 hours prior to euthanasia. Five horses given phenylbutazone alone and four horses subjected to water deprivation alone did not develop papillary necrosis. Urinalyses were normal prior to water deprivation, and also after water deprivation in the horses that did not receive phenylbutazone, but the water-deprived, phenylbutazone-treated horses had many red blood cells, transitional epithelial cells, and large numbers of oxalate crystals in their urine. Ulcera...
Tobin T, Chay S, Kamerling S, Woods WE, Weckman TJ, Blake JW, Lees P.Phenylbutazone is an acidic, lipophilic, non-steroidal anti-inflammatory drug (NSAID). It is extensively metabolized in the horse. The metabolites so far identified, oxyphenbutazone, gamma-hydroxyoxyphenbutazone, account for some 25-30% of administered dose over 24 h. The plasma half-life of phenylbutazone and termination of its pharmacological action are determined primarily by its rate of hepatic metabolism. Phenylbutazone acts by inhibiting the cyclooxygenase enzyme system, which is responsible for synthesis of prostanoids such as PGE2. It appears to act on prostaglandin-H synthase and pros...
