Flunixin Meglumine is a non-steroidal anti-inflammatory drug (NSAID) commonly used in horses to manage pain and inflammation associated with musculoskeletal disorders, colic, and other conditions. It functions by inhibiting the enzyme cyclooxygenase, which is involved in the production of prostaglandins that mediate inflammation and pain. Flunixin Meglumine is administered through various routes, including intravenous and oral formulations, and is noted for its rapid onset of action. The pharmacokinetics, efficacy, and safety profile of Flunixin Meglumine in equine medicine are subjects of ongoing research. This page compiles peer-reviewed research studies and scholarly articles that explore the pharmacological properties, therapeutic applications, and potential side effects of Flunixin Meglumine in horses.
Kohn CW, Muir WW.Comparison of the visceral analgesic effects of xylazine, morphine, butorphanol, pentazocine, meperidine, dipyrone, and flunixin in a cecal distention model of colic pain indicated that xylazine produces the most relief from abdominal discomfort. Repeated administration of xylazine may reduce visceral pain so effectively that the seriousness of abdominal disease is obscured. Xylazine decreased propulsive motility in the jejunum and pelvic flexure of healthy ponies. Morphine and butorphanol also gave relief from visceral pain in the cecal distention model. Morphine may inhibit colonic, and buto...
Belknap J, Arden W, Yamini B.A 2-month-old Standard-bred colt with signs of abdominal pain and large scrotum was found to have septic periorchitis involving the right testis. Surgical exploration of the abdomen and scrotum was performed; the colt was then castrated. Actinobacillus equuli was isolated from specimens obtained at surgery. The colt was treated with broad-spectrum antibiotics and flunixin meglumine after surgery, and fully recovered. The clinical signs of periorchitis in the colt were similar to an inguinal/scrotal hernia.
Traub-Dargatz JL, Bertone JJ, Gould DH, Wrigley RH, Weiser MG, Forney SD.Effects of a therapeutic dose of flunixin meglumine on gastric mucosa of horse foals were determined by endoscopy, double-contrast radiography, and gross and histologic examinations. Foals were administered 1.1 mg of flunixin meglumine/kg of body weight, PO/day for 30 days in an encapsulated form that was divided into 2 doses/day (group 1; n = 3) or by IM injection once a day (group 2; n = 7). Three control foals (group 3; n = 3) were administered capsules (n = 1) containing dextrose powder or IM injections (n = 2) of vehicle solution without flunixin meglumine. All 3 groups-1 foals given flun...
Jaussaud P, Courtot D, Guyot JL, Paris J.The main metabolite of flunixin, a hydroxylated product, has been identified by gas chromatography-mass spectrometry and 1H NMR spectroscopy in equine urine and plasma. The method also permits the qualitative monitoring of the urinary elimination of the drug and its metabolite. The two products are detected up to 175 and 54 h, respectively, after a single intravenous administration at the dose of 1 mg/kg. Simultaneous detection of the two compounds increases the reliability of anti-doping control analysis.
Lavoie JP, Morris DD, Zinkl JG, Lloyd K, Divers TJ.Pancytopenia was evaluated in a mature Quarter Horse gelding. A diagnosis of bone marrow aplasia was made on the basis of bone marrow hypocellularity. History of drugs administered included penicillin, oxytetracycline, trimethoprim-sulfadiazine, phenylbutazone, dipyrone, flunixin meglumine, and isoxsuprine. Clinical remission was observed after treatment with glucocorticoids, androgens, and broad-spectrum antimicrobials.
Roger T, Ruckebusch Y.The contractile activity of the equine large intestine exhibited a biphasic response to feeding: enhancement of migrating complexes passing along the colon and an increase of 50% in cyclic variations in smooth muscle at intervals of 20 min on the left ventral colon for a period of 5 to 7 h postfeeding. The cholinergic agonist, bethanechol (50 micrograms/kg subcutaneously), induced both the migrating complexes and the cyclic variations at intervals of 10-15 min. In contrast, the intra-arterial infusion of PGF2 alpha (3 micrograms/kg/min) increased the contractile activity during infusion, but w...
Craig AM, Blythe LL, Appell LH, Slizeski ML.Dimethyl sulfoxide (DMSO) had been postulated to be a 'masking agent' when used concurrently with therapeutic or prohibited drugs in racing animals. Eight drugs (flunixin, furosemide, caffeine, apomorphine, phenylbutazone, lidocaine, cocaine, and acepromazine maleate) were administered to six horses singly and with concurrent intravenous DMSO. Urine samples were analyzed for the presence of the drugs and/or their metabolites by thin layer chromatography. Direct comparison of thin layer chromatograms of extracts of positive urine samples with and without DMSO verified that DMSO did not interfer...
Pascoe DR, Pascoe RR, Hughes JP, Stabenfeldt GH, Kindahl H.One hundred mares carrying twin conceptuses between gestation days (GD) 12 and 30 were assigned to 4 groups. Group-1 mares (n = 20) were given a placebo (sterile saline solution, IV, and sesame oil, IM). Group-2 mares (n = 32) were given a single dose of progesterone (625 mg, IM) in sesame oil. Group-3 mares (n = 28) were given multiple progesterone treatments (625 mg, IM) at 6-day intervals until GD 42. Group-4 mares (n = 20) were given a single treatment of flunixin meglumine (500 mg, IV) and progesterone (625 mg, IM). Each group was further assigned to equal subgroups A and B according to t...
Turek JJ, Lamar CH, Fessler JF, Bottoms GD.An in vitro system of cultured equine endothelial cells was evaluated as a model for endotoxin (ET) exposure in the horse. Primary cell lines from pulmonary vessels and aortas were cultured from tissues of 6 horses. Effects of ET alone with and without serum and in combination with the cyclo-oxygenase inhibitor flunixin meglumine and isolated equine neutrophils were evaluated by transmission electron microscopy. Cells plus serum were incubated with 10, 25, 50, or 100 micrograms of ET/ml of incubation medium for 1, 3, 8, or 24 hours. Cells without serum were cultured for 1 and 3 hours. Flunixin...
Higgins AJ, Lees P, Sharma SC, Taylor JB.An accurate and reliable method for the separation of flunixin from, and measurement in, equine inflammatory exudate and plasma by high performance liquid chromatography has been developed. Flunixin can be detected in concentrations as low as 0.05 micrograms/ml using an ultraviolet spectrophotometric detector at 285 nm. Samples were acidified with 2M hydrochloric acid and extracted with dichloromethane. The extract was evaporated and reconstituted in acetonitrile. Iminodibenzyl was used as internal standard. The mean recovery of flunixin from plasma was 97.6 +/- 3.9 per cent. Particular advant...
Ward DS, Fessler JF, Bottoms GD, Turek J.Ponies with electromagnetic blood flow transducers implanted around the main pulmonary and left main coronary arteries, were used to evaluate effects of chronic sublethal endotoxin on cardiac output (CO), stroke volume, and left coronary blood flow (LCBF). Plasma thromboxane (TX), as indicated by TXB2, prostacyclin as indicated by 6-keto-prostaglandin (PG) F1 alpha, and hematologic and blood chemical values also were evaluated. Over 24 hours, 2 groups of ponies were given progressively increasing IV and intraperitoneal doses of Escherichia coli lipopolysaccharide (LPS) at 0, 6, 12, and 18 hour...
Dawson J, Lees P, Sedgwick AD.The direct effects of four non-steroidal anti-inflammatory drugs (NSAIDs) on equine polymorphonuclear (PMN) and mononuclear (MN) leucocyte movement were investigated using two in vitro assay systems. The Boyden chamber microfilter technique measures both chemokinetic and chemotactic locomotion, and the agarose microdroplet assay measures solely chemokinesis. Zymosan-activated plasma (ZAP) and the synthetic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) were used as standard chemoattractants for PMN and MN leucocytes, respectively. The actions of six concentrations of each NSAID, indome...
Semrad SD, Moore JN.Previous work has shown repeated low doses of flunixin meglumine (FM) inhibit thromboxane production in normal horses. Enhanced concentrations of thromboxane in serum occurred after the drug therapy was discontinued. Our study was performed to evaluate the effects of low doses of FM in horses repeatedly challenged with endotoxin. Group I horses received E. coli endotoxin (0.1 microgram/kg IV) at 0 and 90 h. Group II horses received endotoxin and were also treated with FM (0.25 mg/kg IV) at 2, 10, 18, 26, 34, and 42 h after the initial administration of endotoxin. Clinical signs of endotoxemia ...
Semrad SD, Hardee GE, Hardee MM, Moore JN.The efficacy of low doses of flunixin meglumine in reducing eicosanoid generation and clinical signs in response to experimentally induced endotoxaemia was investigated. Thromboxane B2 and 6-keto-prostaglandin F1 alpha were measured in serum and plasma by radioimmunoassay. Plasma flunixin concentrations were determined by high performance liquid chromatography and pharmacokinetic parameters derived non-compartmentally. In horses administered flunixin meglumine before endotoxin challenge, a significant suppression in plasma thromboxane B2 and 6-keto-prostaglandin F1 alpha generation was observe...
Templeton CB, Bottoms GD, Fessler JF, Ewert KM, Roesel OF, Johnson MA, Latshaw HS.Shock was induced in four groups of anesthetized ponies with an intravenous injection of Escherichia coli endotoxin [125 micrograms/kg]. Five minutes after endotoxin injection, the ponies were given no treatment (group A), flunixin meglumine (FM:1.1 mg/kg) (group B), dexamethasone (2 mg/kg) (group C), or prednisolone (10 mg/kg) (group D). Additionally, FM was given every 3 hours, and the steroids were given at 3, 9, and 24 hours following endotoxin. Hemodynamic measurements were made during the 4-hour anesthetic period. Blood samples were collected for the analysis of prostaglandins, blood che...
Hardee MM, Moore JN, Hardee GE.The efficacy of three agents which alter the metabolism of arachidonic acid was investigated in normal, conscious horses. A dose response evaluation was made of flunixin meglumine and phenylbutazone, two cyclo-oxygenase inhibitors, and of a selective thromboxane synthetase inhibitor, UK-38,485. Radioimmunoassay of thromboxane B2 (TxB2) and 6-keto prostaglandin F1 alpha (PGF1 alpha) was used to assess the concentrations of thromboxane A2 (TxA2) and prostacyclin (PGI2) respectively, in serum. Flunixin was the most potent inhibitor of serum TxB2 and 6-keto PGF1 alpha production. UK-38,485 also de...
Jaussaud P.Flunixin is a non-steroidal anti-inflammatory agent, with a potent analgesic activity and a slight toxicity. It is largely used in horses, in the form of meglumine salt, for the treatment of inflammatory diseases or colics, and often identified in dopage cases. Physical and chemical properties of the drug, its pharmacological and toxicological properties, and its use in equine species are depicted.
Moore JN, Hardee MM, Hardee GE.Two cyclooxygenase inhibitors (flunixin meglumine and phenylbutazone) and a selective thromboxane synthetase inhibitor were assessed in the management of experimental equine endotoxemia. Drugs or saline solution were administered to 16 horses 15 minutes before administration of a sublethal dose of endotoxin (Escherichia coli 055:B5). Plasma concentrations of thromboxane B2 (TxB2), prostacyclin (6-keto PGF1 alpha), plasma lactate, and hematologic values and clinical appearance were monitored for 3 hours after endotoxin administration. Pretreatment with flunixin meglumine (1 mg/kg of body weight...
Semrad SD, Hardee GE, Hardee MM, Moore JN.The pharmacokinetics and inhibition of prostaglandin synthesis in conscious horses given various dosages of flunixin meglumine were studied. Plasma concentrations of flunixin were measured by high-performance liquid chromatography, and serum thromboxane B2 and 6-keto prostaglandin F1 alpha were quantitated by radioimmunoassay. Within the dosage range studied, linear pharmacokinetics were achieved. After IV administration of flunixin (1.1 mg/kg, 0.25 mg/kg, 0.1 mg/kg), significant suppression of serum thromboxane generation persisted for 12, 4, and 3 hours, respectively. Repeated administration...
Olson NC, Meyer RE, Anderson DL.The effects of endotoxemia on cardiopulmonary parameters, before and after cyclooxygenase blockade, were determined in anesthetized ponies spontaneously breathing a mixture of halothane and 100% O2. Escherichia coli endotoxin was infused intravenously at 20 micrograms/kg for 1 h followed by 10 micrograms X kg-1 X h-1 the subsequent 4 h. By 15 min endotoxin increased mean pulmonary arterial pressure (Ppa), pulmonary vascular resistance (PVR), and alveolar dead space ventilation (VDA/VT), and these were followed by a return to base-line values by 30 min. A second increase in PVR occurred by 5 h ...
Dunkle NJ, Bottoms GD, Fessler JF, Knox K, Roesel OF.A study was conducted to determine whether body fluids undergo a net shift from one compartment to another during endotoxin-induced shock in the pony, and whether flunixin meglumine alters these endotoxin-induced changes in the volumes of body fluid compartments. Total blood, RBC, and plasma volumes were determined, using 51Cr-labeled RBC and PCV that were corrected for trapped plasma. Total body water was measured by distribution of 3HOH. Arterial blood pressure was measured directly, using a blood pressure transducer. Treatment (flunixin meglumine, 1.1 mg/kg of body weight) was given to 6 of...
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...
Turek JJ, Templeton CB, Bottoms GD, Fessler JF.Endotoxic shock was induced in 5 ponies by intraperitoneal injections of 20, 40, 60, 80, and 80 micrograms of Escherichia coli endotoxin (LPS)/kg of body weight at 0, 6, 12, 18, and 24 hours, respectively. At 24 hours, the ponies also were given 20 micrograms of LPS/kg via catheter in the left ventricle of the heart. A 2nd group of 4 ponies was given 1.1 mg of flunixin meglumine (FM)/kg, IV, at 6, 12, 18, and 24 hours just before the corresponding LPS injection. Two hours after the 24-hour LPS injection, the ponies in both groups were anesthetized, the lungs were perfused with fixative, and po...
Templeton CB, Bottoms GD, Fessler JF, Turek JJ, Boon GD.The objectives of this study were to determine the pathophysiological effects of increasing amounts of endotoxin administered intraperitoneally (IP) for 24 hr at which time an intravenous (IV) injection of endotoxin was given. The ability of flunixin meglumine (FM), a nonsteroidal antiinflammatory drug with antiprostaglandin activity, to provide protective effects was also determined. Eight ponies were divided into two groups of four ponies each; one group (untreated) received endotoxin only and the other group (treated) received endotoxin while being treated with flunixin. Hemodynamic and ser...
Bottoms GD, Johnson MA, Lamar CH, Fessler JF, Turek JJ.Dispersed equine vascular endothelial cells grown in tissue culture, and freshly isolated neutrophils were used to determine direct effects of endotoxin on cyclooxygenase and lipoxygenase products. Endothelial cells (10(7)/ml) or neutrophils (2 X 10(6)/ml) were incubated with (a) buffer, (b) endotoxin (10 micrograms/ml), (c) endotoxin + flunixin meglumine (10 micrograms/ml), or (d) calcium ionophore, A23187 (10 micrograms/ml). Thromboxane (TxB2), prostacyclin (6-keto-PGF1 alpha), and leukotriene C4 (LTC4) were determined in the incubation fluid by radioimmunoassay. Thromboxane and prostacyclin...
Ewert KM, Fessler JF, Templeton CB, Bottoms GD, Latshaw HS, Johnson MA.To evaluate the effect of certain drugs on hematologic changes, blood chemical values, and survival in endotoxin shock, anesthetized ponies were given (IV) endotoxin (Escherichia coli O55:B5) and then treated as follows: Group A ponies--given a saline infusion at 5 minutes and at 3 hours after they were given endotoxin; group B ponies--given flunixin meglumine at 5 minutes and at 3, 6, 9, and 24 hours after they were given endotoxin; group C ponies--treated with dexamethasone; and group D ponies--treated with prednisolone at 5 minutes and at 3, 9, and 24 hours after they were given endotoxin. ...
Lees P, Higgins AJ.A model of acute inflammation was used in a cross-over study in Welsh mountain ponies to assess the actions of flunixin meglumine on selected components of a localised inflammatory reaction induced by injecting 0.5 ml of a 2 per cent carrageenin solution into subcutaneously implanted tissue cages. Samples of exudate were harvested at predetermined times between three and 48 hours. Increases in leucocyte numbers and protein concentration were not prevented by flunixin treatment. Prostaglandin E2-like activity was present in exudates from untreated ponies with the highest mean concentration occu...
Pascoe DR, Pascoe RR, Hughes JP, Stabenfeldt GH, Kindahl H.One hundred mares carrying twin conceptuses between gestation days (GD) 12 and 30 were assigned to 4 groups. Group-1 mares (n = 20) were given a placebo (sterile saline solution, IV, and sesame oil, IM). Group-2 mares (n = 32) were given a single dose of progesterone (625 mg, IM) in sesame oil. Group-3 mares (n = 28) were given multiple progesterone treatments (625 mg, IM) at 6-day intervals until GD 42. Group-4 mares (n = 20) were given a single treatment of flunixin meglumine (500 mg, IV) and progesterone (625 mg, IM). Each group was further assigned to equal subgroups A and B according to t...
Soma LR, Behrend E, Rudy J, Sweeney RW.The disposition of flunixin meglumine administered IV at a dosage of 1.1 mg/kg was described by a 2-compartment model; the alpha and beta half-lives (t1/2) were 0.61 and 1.5 hours, respectively. When administered IV at a rate of 2.2 mg/kg, the disposition was best described by a 3-compartment model, and the alpha, beta, and lambda t1/2 were 0.16, 1.52, and 6.00 hours, respectively. The zero-time plasma concentrations after flunixin meglumine was administered at 1.1 and 2.2 mg/kg were 9.3 +/- 0.76 and 21.5 +/- 7.4 mg/L, respectively. The bioavailability after oral administration of 1.1 mg/kg wa...
MacAllister CG, Sangiah S, Mauromoustakos A.Using video gastroscopy, the efficacy of a Histamine-H2 type receptor antagonist (WY 45, 727) was investigated in young ponies with spontaneous and experimentally induced gastric ulcers. Oral administration of WY 45, 727 at 2 mg/kg and 10 mg/kg of body weight every 12 hours for 14 days resulted in complete healing of spontaneous gastric ulcers in the non-glandular portion of the stomach in 2/5 (40%) and 3/4 (75%) of the ponies, respectively, compared (P < 0.05) to 0/5 (0%) placebo-treated ponies. After intramuscular administration of flunixin meglumine at 1.5 mg/kg body weight every 8 hours fo...
Borer KE, Clarke KW.To determine whether hyoscine has a sparing effect on the volume of dobutamine required to maintain mean arterial pressure (MAP) at 70 mmHg in horses anaesthetized with halothane. Methods: Prospective, randomized, controlled clinical trial. Methods: Twenty adult horses weighing 507 +/- 97 kg (mean +/- SD), aged 10 +/- 5 years. Methods: Pre-anaesthetic medication in all horses was intramuscular (IM) acepromazine (40 mug kg(-1)) and intravenous (IV) detomidine (0.02 mg kg(-1)). Anaesthesia was induced with ketamine (2.2 mg kg(-1) IV) and diazepam (0.02 mg kg(-1) IV), and maintained with halothan...
Southwood LL.Horses with large colon volvulus (LCV) often require intensive postoperative medical management. Although early referral and surgical intervention are critical for minimal postoperative complications and a successful outcome, this is often not possible for many reasons. Endotoxemia, extensive mucosal damage with subsequent severe hypoproteinemia, and focal ischemic necrosis are the major causes of postoperative morbidity and mortality. Although fluid therapy, flunixin meglumine, and antimicrobials are still the mainstay of perioperative management, synthetic colloids are being used to maintain...
Colahan PT, Bailey JE, Chou CC, Johnson M, Rice BL, Jones GL, Cheeks JP.Twelve clinically sound, healthy, athletically conditioned Thoroughbred horses were subjected to an incremental exercise stress test to determine the effects and period of detection of a single dose of flunixin meglumine (1.1 mg/kg by intravenous injection) in serum and urine by ELISA. Flunixin concentrations, performance, and hematologic and clinical chemical parameters were measured. All horses were rotated through four treatment groups of a Latin-square design providing for each horse to serve as its own control. Flunixin meglumine reduced prostaglandin F(1alpha) and thromboxane concentrati...
Fessler JF, Bottoms GD, Roesel OF, Moore AB, Frauenfelder HC, Boon GD.A study was made of flunixin meglumine (FM), an analgesic agent with antiprostaglandin activity, in the management of endotoxin-induced changes in ponies. Three groups of 5 ponies each were used: A--controls, B--nontreated ponies with endotoxin-induced shock, and C--ponies with endotoxin-induced shock treated with FM. Shock was induced in anesthetized ponies with IV injections of Escherichia coli endotoxin. Disruption of glucose homeostasis, insulin levels, hemograms, aerobic metabolism, and cell damage as indicated by plasma enzymes were observed. Treatment with FM (5 minutes) after shock was...
Landoni MF, Foot R, Frean S, Lees P.The objective of this study was to analyse the effects of 4 nonsteroidal anti-inflammatory drugs (NSAIDs) on the production of beta-glucuronidase (beta-glu), tumour necrosis factor alpha (TNF alpha), interleukin-6 (IL-6), interleukin-1 (IL-1) and prostaglandin E2 (PGE2) by lipopolysaccharide (LPS)-stimulated equine synoviocytes. The agents studied were flunixin, tolfenamic acid, S(+)ketoprofen (KTP) and R(-)ketoprofen. LPS-induced release of beta-glu from synoviocytes was inhibited in a concentration dependent manner by all 4 compounds, tolfenamic acid being the most potent. Of the 2 KTP enant...
Kindahl H, Daels P, Odensvik K, Daunt D, Fredricksson G, Stabenfeldt G, Hughes JP.Three different routes of administering Salmonella typhimurium endotoxin to mimic naturally occurring endotoxaemia were tried in the mare. Bolus injection, repeated bolus injections and continuous low-dose infusion were compared with prostaglandin F2 alpha release, leucocyte count and clinical response. A biphasic prostaglandin release and a pronounced leucopenia of almost identical patterns were seen in all models. Repeated bolus injections showed that the second injection initiated only a small prostaglandin release indicating the development of refractoriness to the treatment. A similar ref...
Luo Y, Rudy JA, Uboh CE, Soma LR, Guan F, Enright JM, Tsang DS.The method describes quantification and confirmation of flunixin in equine plasma by liquid chromatography-quadrupole time-of-flight mass spectrometry (LC/Q-TOF/MS/MS). Samples were screened by enzyme-linked immunosorbent assay (ELISA) and only those samples presumptively declared positive were subjected to quantification and confirmation for the presence of flunixin by this method. The method is also readily adaptable to instrumental screening for the analyte. Flunixin was recovered from plasma by liquid-liquid extraction (LLE). The sample was diluted with 2 ml saturated phosphate buffer (pH ...
Knych HK, Arthur RM, McKemie DS, Chapman N.Flunixin meglumine is commonly used in horses for the treatment of musculoskeletal injuries. The current ARCI threshold recommendation is 20 ng/mL when administered at least 24 h prior to race time. In light of samples exceeding the regulatory threshold at 24 h postadministration, the primary goal of the study reported here was to update the pharmacokinetics of flunixin following intravenous administration, utilizing a highly sensitive liquid chromatography-mass spectrometry (LC-MS). An additional objective was to characterize the effects of flunixin on COX-1 and COX-2 inhibition when drug con...
Lees P, Higgins AJ.A model of acute inflammation was used in a cross-over study in Welsh mountain ponies to assess the actions of flunixin meglumine on selected components of a localised inflammatory reaction induced by injecting 0.5 ml of a 2 per cent carrageenin solution into subcutaneously implanted tissue cages. Samples of exudate were harvested at predetermined times between three and 48 hours. Increases in leucocyte numbers and protein concentration were not prevented by flunixin treatment. Prostaglandin E2-like activity was present in exudates from untreated ponies with the highest mean concentration occu...
Easterwood L, Chaffin MK, Marsh PS, Porter B, Barr C.66 horses were potentially exposed to phosphine (a gas) 14 hours after being fed a pelleted ration treated with aluminum phosphide. Results: 28 horses had clinical signs of profuse sweating, tachycardia, tachypnea, pyrexia, ataxia, seizures, and widespread muscle tremors. Clinically relevant laboratory findings included hypoglycemia and high plasma concentrations of lactate and ammonia and activities of gamma-glutamyl transpeptidase, aspartate aminotransferase, and alkaline phosphatase. At least 4 horses had signs consistent with hepatic encephalopathy. Necropsy findings included petechial and...
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...
el-Banna HA.The pharmacokinetic aspects of sulphadimidine were studied in clinically healthy (control) and Flunixin-medicated horses after a single intravenous and oral administration of 100 mg/kg body weight. Plasma sulphadimidine concentration were determined by high-performance liquid chromatography (HPLC). Following the intravenous injection, all plasma sulphadimidine data were best approximated by a two-compartment open model using sequential, weight non-linear regression. Flunixin induced a 67% increase in the rate of sulphadimidine return to the central compartment from peripheral tissues (K21) and...
Thomasy SM, Slovis N, Maxwell LK, Kollias-Baker C.This study investigated the pharmcokinetics, efficacy, and safety of the fentanyl transdermal therapeutic system (TTS) in horses in which there was an inadequate analgesic response to nonsteroidal anti-inflammatory drugs (NSAIDs) alone. Nine horses with pain that was refractory to therapeutic doses of phenylbutazone (n = 3) or flunixin meglumine (n = 6) subsequently also received between 39 and 110 microg/kg of transdermal fentanyl. Blood samples were collected at 0, 1, 2, 3, 4, 5, 6, 12, 24, 36, 48, 60, and 72 hours after patch application, and a radioimmunoassay was used to determine serum f...
Abutarbush SM, Alfaqeeh SM, Mustafa G, Qura'n L, Al-Majali AM.To evaluate the ability of atropine sulfate, butylscopolammonium bromide combined with metamizole sodium, and flunixin meglumine to ameliorate the clinical adverse effects of imidocarb dipropionate in horses. Methods: 28 horses with piroplasmosis. Methods: 28 horses were randomly assigned to 4 equal groups according to the pretreatment administered. Fifteen minutes before administration of 2.4 mg of imidocarb dipropionate/kg IM, horses in the first group were pretreated with 0.02 mg of atropine sulfate/kg IV, the second group with a combination of 0.2 mg of butylscopolammonium bromide/kg IV an...
Clegg PD, Jones MD, Carter SD.Loss of articular cartilage, which is the most important pathological lesion occurring in osteoarthritis, has been shown to be enzymatically mediated. The matrix metalloproteinases (MMPs) are a group of enzymes which have been implicated in this degradation of articular cartilage matrix. The use of pharmacological agents to inhibit this catabolic process in the joint is a potential route for therapeutic intervention. The gelatinase MMPs, MMPs-2 and 9, were purified by affinity chromatography from equine cell cultures. The ability of phenylbutazone, flunixin, betamethasone, dexamethasone, methy...
Bottoms GD, Johnson MA, Lamar CH, Fessler JF, Turek JJ.Dispersed equine vascular endothelial cells grown in tissue culture, and freshly isolated neutrophils were used to determine direct effects of endotoxin on cyclooxygenase and lipoxygenase products. Endothelial cells (10(7)/ml) or neutrophils (2 X 10(6)/ml) were incubated with (a) buffer, (b) endotoxin (10 micrograms/ml), (c) endotoxin + flunixin meglumine (10 micrograms/ml), or (d) calcium ionophore, A23187 (10 micrograms/ml). Thromboxane (TxB2), prostacyclin (6-keto-PGF1 alpha), and leukotriene C4 (LTC4) were determined in the incubation fluid by radioimmunoassay. Thromboxane and prostacyclin...
Galbraith EA, McKellar QA.Flunixin was highly protein bound in the serum of dogs (92.2 per cent), goats (84.8 per cent) and horses (86.9 per cent). Meclofenamic acid was also highly protein bound, although there were larger differences between the extent of the binding in dogs (90.3 per cent), goats (84.7 per cent) and horses (99.8 per cent). Both flunixin and meclofenamic acid were potent inhibitors of the in vitro generation of thromboxane (Tx) B2 in blood. Flunixin inhibited the generation of TxB2 by 50 per cent of the maximum response (IC50) in dog, goat and horse blood at concentrations of 0.10, 0.02 and 0.04 micr...
Black JB, Frampton AR.Equine herpesvirus type 1 (EHV-1) is a highly transmissible pathogen that leads to a variety of clinical disease outcomes in infected horses. A major sequela that can occur after an EHV-1 infection is a neurological disease termed equine herpesvirus myeloencephalopathy (EHM). Clinical manifestations of EHM include fever, ataxia, incontinence, and partial to full paralysis, which may ultimately lead to the euthanization of the infected horse. To develop an effective treatment strategy for EHM, it is critical that the specific virus-host interactions that lead to EHM be investigated so that safe...
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 ...
Adams SB, Lamar CH, Masty J.Bipolar stainless steel electrodes were surgically implanted in 4 ponies to record myoelectrical and mechanical activity of the distal portion of the jejunum and pelvic flexure. After determining normal activity, the effects of neostigmine, xylazine, flunixin meglumine, dipyrone, panthenol, and atropine sulfate were determined. Flunixin meglumine, dipyrone, and panthenol had no effect on the motility of the jejunum or pelvic flexure. Xylazine and atropine sulfate decreased motility of the distal portion of the jejunum and pelvic flexure, with atropine sulfate having a greater effect and lastin...
Dirikolu L, Woods WE, Boyles J, Lehner AF, Harkins JD, Fisher M, Schaeffer DJ, Tobin T.Injuries sustained by horses during racing have been considered as an unavoidable part of horse racing. Many factors may be associated with the musculoskeletal injuries of Thoroughbred race horses. This study surveyed the amounts of nonsteroidal anti-inflammatory agents (NSAIDs) in injured horse's biological system (plasma) at Kentucky racetracks from January 1, 1995 through December 31, 1996. During that period, there were 84 catastrophic cases (euthanized horses) and 126 noncatastrophic cases. Plasma concentrations of NSAIDs were determined by High Performance Liquid Chromatography in injure...
Coakley M, Peck KE, Taylor TS, Matthews NS, Mealey KL.To compare serum disposition of flunixin meglumine after i.v. administration of a bolus to horses, donkeys, and mules. Methods: 3 clinically normal horses, 5 clinically normal donkeys, and 5 clinically normal mules. Methods: Blood samples were collected at time zero (before) and 5, 10, 15, 30, and 45 minutes, and at 1, 1.25, 1.5, 1.75, 2, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 5.5, 6, and 8 hours after i.v. administration of a bolus of flunixin meglumine (1.1 mg/kg of body weight). Serum was analyzed in duplicate by the use of high-performance liquid chromatography for determination of flunixin meglumi...
King JN, Gerring EL.Post operative ileus is a serious complication of abdominal surgery in horses and there is evidence that endotoxin plays a significant role in its pathogenesis. Pre-treatment with intravenous (i.v.) flunixin (1.1 mg/kg bodyweight [bwt]) or phenylbutazone (4.4 mg/kg bwt) significantly antagonised the acute disruption of gastric, small intestinal and large intestinal motility induced by 0.1 microgram/kg bwt i.v. endotoxin in ponies implanted with gastrointestinal strain gauges. Phenylbutazone was more effective than flunixin and this was significant (P < 0.01) for the stomach and left dorsal col...
Ward DS, Fessler JF, Bottoms GD, Turek J.Ponies with electromagnetic blood flow transducers implanted around the main pulmonary and left main coronary arteries, were used to evaluate effects of chronic sublethal endotoxin on cardiac output (CO), stroke volume, and left coronary blood flow (LCBF). Plasma thromboxane (TX), as indicated by TXB2, prostacyclin as indicated by 6-keto-prostaglandin (PG) F1 alpha, and hematologic and blood chemical values also were evaluated. Over 24 hours, 2 groups of ponies were given progressively increasing IV and intraperitoneal doses of Escherichia coli lipopolysaccharide (LPS) at 0, 6, 12, and 18 hour...
Foreman JH, Bergstrom BE, Golden KS, Roark JJ, Coren DS, Foreman CR, Schumacher SA.There are no refereed controlled documentations of the skeletal analgesic efficacy of different dosages of flunixin meglumine (FM). Objective: The objective of this experiment was to compare the efficacy of various dosages of FM with a negative control. The hypothesis was that higher doses would result in improved efficacy in a dose-dependent manner when tested in a reversible model of foot lameness. Methods: Ten horses shod with adjustable heart bar shoes had weekly modified AAEP grade 4.0/5.0 lameness induced by tightening a set screw against the heart bar. Heart rate (HR) and lameness score...
Foreman JH, Ruemmler R.Using an adjustable heart bar shoe model of foot pain, the objective of this study was to test the hypothesis that the combined use of phenylbutazone (PBZ) and flunixin meglumine (FM) would prove more efficacious in alleviating lameness than either drug alone. Methods: One hour after induction of lameness at weekly intervals, 8 healthy adult Thoroughbred horses randomly underwent one of 4 i.v. treatments: saline (SAL) placebo (1 ml/45 kg bwt), PBZ (4.4 mg/kg bwt), FM (1.1 mg/kg bwt) or PBZ+FM (at the same dosages as given individually). Heart rate (HR) and lameness score (LS) responses were as...
Potocnik E, Drozdzewska K, Schwarz B.We describe the case of a four-year-old Quarter Horse mare that presented with fever, respiratory infection with productive cough, disorientation, and bilateral anterior uveitis with discharge that had been previously treated with trimethoprim-sulfadiazine (TMPS). Acinetobacter johnsonii was cultured from an endoscopic tracheal wash. Treatment was initiated with cefquinome, systemic flunixin-meglumine, local ocular atropine, and corticosteroids. On subsequent days, the mare exhibited bilateral edematous, painful swelling of the face, primarily affecting the eyelids and lips. There were neither...
