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.
Baxter GM, Moore JN.Different dosages of aspirin were administered (by nasogastric tube) to 3 groups of 5 healthy adult horses to determine the minimal effective dosage needed to decrease serum thromboxane B2 (TxB2) concentrations and to determine the duration of this decrease. When compared with their base-line serum TxB2 concentrations, horses in group 1 (given 5 mg/kg) had a 71% decrease in TxB2 concentrations at 24 hours after aspirin was given and a 86% decrease at 48 hours; serum TxB2 concentrations were back to base-line values by 120 hours. Horses in group 2 (given 10 mg/kg) had a 60% decrease in TxB2 con...
Higgins AJ, Lees P, Sedgwick AD, Buick AR, Churchus R.In a two-part cross-over experiment in six ponies, an acute inflammatory reaction was generated by injecting carrageenin solution into subcutaneously-implanted tissue-cages lined with fibrovascular granulation tissue. In each part of the cross-over, half of the ponies received a novel phenylpyrazoline anti-inflammatory agent (BW540C) orally and half received a placebo treatment. BW540C inhibited platelet cyclo-oxygenase for 24 h but the reductions in exudate eicosanoid concentrations were less pronounced. A significant suppression in the rise of surface skin temperature in BW540C-treated ponie...
Lees P, Higgins AJ.In a 12-day treatment schedule, 5 ponies were given orally a paste formulation of phenylbutazone (PBZ) and 5 matched ponies were given equivalent doses of a placebo paste. On day 12, a mild, nonimmune inflammatory reaction was induced subcutaneously in the neck of each pony by inserting sterile, polyester sponge strips soaked in a 2% carrageenan solution. Exudate was collected at 4, 8, 12, and 24 hours by serial removal of sponges. There were no significant (P less than 0.05) differences in exudate protein concentration and leukocyte numbers between the treatment groups, but the group given PB...
Becht JL, Byars TD.Gastroduodenal ulceration is becoming recognised as an important disease in foals during the first few months of life. Aetiopathogenesis is presumed to be similar to peptic disease in humans associated with back diffusion of hydrogen ions into the mucosa. Many factors have been incriminated as predisposing foals to ulceration but few have been proven. To date, use of non-steroidal anti-inflammatory agents has been the only documented cause of gastroduodenal ulceration in foals. The clustering of affected foals on certain farms suggests an infectious aetiology but attempts to identify a causati...
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...
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...
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.
Black HE.Non-steroidal anti-inflammatory drugs represent the most heavily prescribed and used class of drugs in human medicine. Most are derivatives of either salicylates, propionic acid, indoleacetic acid, anthranilic acid, pyrazolone, or oxicams. They depress the synthesis of prostaglandins from arachidonic acid by reversible inhibition of the enzyme cyclooxygenase. In the kidney, prostaglandins PGE2 and PGI2 modulate the vasoconstrictor effects of angiotensin II, norepinephrine, and vasopressin. In the presence of volume contraction, anesthesia, or disease states associated with high levels of these...
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...
Christensen JM, Blythe LL, Craig AM.Phenylbutazone was administered to six Thoroughbred horses in a cross-over study in which the horses received cimetidine pretreatment or no cimetidine pretreatment. Blood samples were collected at various times for 48 h after phenylbutazone administration and the plasma was analysed for phenylbutazone. Cimetidine pretreatment elevated phenylbutazone plasma concentrations during the first 8 h after phenylbutazone administration. The absorption rate, maximum phenylbutazone plasma concentrations and AUC were significantly greater with cimetidine pretreatment. The half-life of phenylbutazone did n...
Woods WE, Chay S, Houston T, Blake JW, Tobin T.The efficacy of testing for illegal drugs in race horses was surveyed by evaluating 27 questionnaires received from 28 racing jurisdictions polled. Large variations in the number of samples tested and drugs detected were reported. Some jurisdictions reported only illegal medications, whereas others also reported permitted medications. To facilitate comparison, stimulants, depressants, local anesthetics, narcotic analgesics, and tranquilizers were classified as hard drugs. Other drugs, which are legal in some jurisdictions, were classified as soft. To evaluate the efficacy of testing, positive ...
Ross MW, Martin BB, Donawick WJ.The case records of 23 horses with cecal perforation (CP) were reviewed. The horses averaged 4.5 years of age (6 weeks to 13 years) and included 9 intact males, 12 mares, and 2 geldings. Twelve of the horses were Standardbreds, 9 were Thoroughbreds, and 1 each, a Belgian and Morgan. The horses were allotted to 2 groups: group I-13 hospitalized horses in which CP occurred unexpectedly, and group II-10 horses with CP at the time of admission. The horses characteristically had been sick or affected with disease unrelated to the cecum. Sixteen horses had been given nonsteroidal anti-inflammatory d...
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...
Woods WE, Chay S, Houston T, Blake JW, Tobin T.Interference or 'masking' in thin layer chromatography occurs when the presence of one drug on a thin layer plate physically obscures or interferes with the detection of another drug. We investigated the ability of phenylbutazone and oxyphenbutazone to mask or interfere with the detection by high performance thin layer chromatography (HPTLC) of basic drugs used illegally in horse racing. Of fifty-five basic drugs called 'positive' since 1981 by laboratories affiliated with the Association of Official Racing Chemists (AORC), forty did not comigrate with phenylbutazone or oxyphenbutazone and cou...
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...
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...
Ungemach FR.Doping in performance horses is defined as the "illegal application of any substance, except normal diet, that might modify the natural and present capacities of the horse at the time of the race." The prohibition of doping is mainly based on the protection of animals. Doping can be performed with various aims: "doping to win" can be regarded as the classical method by mobilization of overphysiological capacities. Such positive doping may be classified as an acute form using psychomotoric stimulants, as a chronic form using anabolic hormones, and as a paradoxical form using small doses of neur...
Todhunter RJ, Stick JA, Trotter GW, Boles C.Esophageal strictures developed in 7 horses that were treated for esophageal obstruction. A soft diet was fed to all horses, with intermittent nasogastric tube feeding in one, and medication included nonsteroidal anti-inflammatory drugs. Maximal reduction in esophageal lumen diameter was evident by 30 days following circumferential esophageal ulceration, after which lumen diameter increased rapidly. Five horses were clinically normal by 60 days after the esophageal injury. Two horses were euthanatized at the owner's request, 16 and 17 days after the original insult.
Higgins AJ, Lees P, Taylor JB.In a two part cross-over experiment, acute inflammatory exudates were induced in 7 ponies by subcutaneous implantation of 3 sterile carrageenin-soaked polyester sponge strips. Treatment comprised a single therapeutic geenin-soaked polyester sponge strips. Treatment comprised a single therapeutic dose of 4.4 mg/kg phenylbutazone (PBZ) administered intravenously at the time of sponge implantation. Exudates were harvested at 6, 12 and 24 hours and examined for leukocyte and erythrocyte numbers using the improved Neubauer technique; for eicosanoids by radioimmunoassay and by high performance liqui...
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...
Moss M S..A review of positive Jockey Club "dope tests" during the 12 years from 1970 to 1981 inclusive is presented and a comparison made with certain overseas racing authorities for varying periods between 1975 and 1981. Urinary pH of post race urine samples is predominantly acidic (although varying in a significant manner throughout the year) and thus favours excretion of the generally more potent basic drugs. The proportion of positive results was about the same in winners and non-winners, ie, one in 400 horses sampled. Drugs found fell mainly into four categories: methylxanthines; non-steroidal ant...
Read WK.Thirty-five cases of renal medullary crest necrosis morphologically similar to the renal papillary necrosis of analgesic nephropathy as described in man and rats are reported in horses receiving maintenance dosages of phenylbutazone. The primary lesion is a well-demarcated focal medullary necrosis resulting in sequestration of fragments of the renal crest. Renal cortical lesions are considered secondary to the medullary necrosis and consist of segmental pallor as a result of tubular dilatation, filtrate retention, and interstitial edema. Ischemia in concert with phenylbutazone is suggested as ...
Acland HM, Gunson DE, Gillette DM.Seven foals aged 18 days to 3 1/2 months had either single or multiple full-circumference segments or long antimesenteric bands of necrotizing duodenitis, sharply delineated from adjacent viable duodenum. Perforation of the necrotic wall had occurred in all foals, leading to acute fibrinous peritonitis. On the mucosal surface severe diffuse, acute inflammation and ulceration involved the anterior half of the duodenum. Two further foals, aged 28 and 30 days, had lesions that are believed to be a chronic form of this disease. Both foals had a thickened duodenal wall, with large areas of mucosa r...
Marshall JF, Bhatnagar AS, Bowman SG, Morris NN, Skorich DA, Redding CD, Blikslager AT.Flunixin meglumine is used for treatment of equine colic despite evidence of inhibited recovery of mucosal barrier function following small intestinal ischaemic injury. This study aimed to characterise an alternative treatment (AHI-805) for abdominal pain in the horse. Objective: To determine the effect of AHI-805, an aza-thia-benzoazulene derivative, on the cyclooxygenase enzymes and the recovery of mucosal barrier function following ischaemic injury. Methods: Effect of AHI-805 on in vitro COX-1 and COX-2 activity was determined by measuring coagulation-induced thromboxane B(2) (TXB(2)) and l...
Aboul-Enein HY, Van Overbeke A, Vander Weken G, Baeyens W, Oda H, Deprez P, De Kruif A.Racemic ketoprofen is a non-steroidal anti-inflammatory drug used to treat musculoskeletal and colic conditions in horses. The enantioselective chiral inversion of ketoprofen administered to horses has been studied by use of cellulose tris(4-methylbenzoate), also known as Chiralcel OJ-R, as chiral stationary phase; acetonitrile - 0.02 M perchlorate buffer (pH 2.0)-methanol, 60:15:25 (v/v/v) was used as mobile phase. Before chromatography, to effect adequate chiral interaction with the chiral stationary phase ketoprofen was derivatized with 9-aminophenanthrene, under acid conditions, after soli...
Marland A, Sarkar P, Leavitt R, Lee-Ruff E, Ramnauth J.A method for the extraction of oxaprozin from equine urine and serum and its quantitation by high-performance liquid chromatography-ultraviolet detection is presented. Confirmation of oxaprozin in postadministration extracts was accomplished by gas chromatographic- mass spectrometric analysis of methylated extracts or liquid chromatography with tandem mass spectrometry daughter ion mass spectra of underivatized extracts. Daypro, a formulation of oxaprozin, was administered orally at a dose of 4.8 g to four standardbred mares. Urine and serum samples were collected to 120 h postadministration. ...
Kallings P, Johnston C, Drevemo S.An often discussed and controversial issue is the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on performance. The purpose of this study was to investigate the effect of the NSAID flunixin on the movement pattern and performance capacity of Standardbred trotters using a standardised track model. Five adult Standardbred horses in training trotted at 2 occasions with a 2 week interval on the same oval dirt track. Before each occasion the horses were either injected with flunixin meglumine (Finadyne) or normal saline solution i.m. 4 h before the performance test (double blind crossover...
Jaraiz MV, Rodriguez C, San Andres MD, Gonzalez F, San Andres MI.Suxibuzone (SBZ), a nonsteroidal anti-inflammatory drug, was administered to 6 horses at a dose rate of 7.5 mg/kg bwt by intravenous (i.v.) route. Plasma and synovial fluid concentrations of suxibuzone and its main active metabolites, phenylbutazone (PBZ) and oxyphenbutazone (OPBZ), were measured simultaneously by a sensitive and specific high-performance liquid chromatographic method. The pharmacokinetic parameters were determined by noncompartmental analysis. Plasma SBZ concentrations rapidly decreased and were not detectable beyond 20 min after treatment. The parent drug was not detected in...
Delbeke FT, Landuyt J, Debackere M.Concentrations of the non-steroidal anti-inflammatory drug (NSAID) alclofenac were determined by a sensitive high performance liquid chromatographic procedure in plasma and urine of horses following oral administration of a dose of 3 g. In plasma, alclofenac was present in detectable concentrations for 72 h. The plasma disposition in individual horses was best described by a bi-compartmental model with two successive rate constants ka1 = 0.05 +/- 0.06 h-1 and ka2 = 0.06 +/- 0.01 h-1. Alclofenac half-lives t1/2 alpha and t1/2 beta were 1.0 +/- 0.8 h and 6.9 +/- 1.5 h, respectively. Maximal conc...
Higgins AJ, Lees P, Taylor JB.In a two part cross-over experiment, acute inflammatory exudates were induced in 7 ponies by subcutaneous implantation of 3 sterile carrageenin-soaked polyester sponge strips. Treatment comprised a single therapeutic geenin-soaked polyester sponge strips. Treatment comprised a single therapeutic dose of 4.4 mg/kg phenylbutazone (PBZ) administered intravenously at the time of sponge implantation. Exudates were harvested at 6, 12 and 24 hours and examined for leukocyte and erythrocyte numbers using the improved Neubauer technique; for eicosanoids by radioimmunoassay and by high performance liqui...
Thomas DP, Foley JP.Detection of prohibited substances in equestrian sports typically involves time-consuming and tedious sample-preparation methods. Micellar LC (MLC) allows for direct injection of equine serum to detect prohibited NSAIDs. Results: The method was linear over the range of standards examined, with recoveries of 94.2-95.1% for phenylbutazone (12-18 µg/ml), and 83.9-88.7% and 87.9-105.0% for diclofenac and flunixin, respectively (0.1-1.2 µg/ml). The limit of detection was 0.1 µg/ml for all compounds and the limit of quantitation was 0.2 µg/ml for phenylbutazone and 0.3 µg/ml for diclofenac and ...
Delbeke FT, Vynckier L, Debackere M.A high performance liquid chromatographic method is described to determine the anti-inflammatory drug suxibuzone (SXB) and its major metabolites phenylbutazone (PBZ) and oxyphenbutazone (OPBZ) in equine plasma and urine. When suxibuzone (6 mg/kg) was administered intravenously (i.v.) or orally (p.o.) no parent drug was detected in plasma or in urine. The disposition of the metabolite PBZ (i.v.) could be described by a 2 compartment model with a beta half-life varying from 7.40 to 8.35 h. Due to severe side effects the use of i.v. suxibuzone should not be encouraged in the horse. PBZ and OPBZ w...
Sager M.The aim of this article is to emphasize the need for analgesic medication in animals in possibly painful situations, especially in the postoperative period. The two large groups of compounds used as analgesics--the opiates and the nonsteroidal antiinflammatory drugs (NSAIDs)--are described with special reference to their pharmacokinetics, side-effects and toxicity, their mechanism of action, their indications and contraindications. Recommended doses of the different drugs available are given for the dog, the cat, the horse, the swine and the small and large ruminants.
Mitten LA, Hinchcliff KW, Pate JL.The effect of inhibition of cyclooxygenase activity on the hemodynamic response to exertion was examined in 6 horses. Rates of O2 consumption and CO2 production and carotid, pulmonary arterial, and right atrial pressures were measured while the horses performed a standardized exercise test on a treadmill after treatment with phenylbutazone or a placebo. Phenylbutazone (8.8 mg/kg p.o. for 2 days and 4.4 mg/kg i.v. 60 min before exertion) abolished the exertion-induced increases in plasma 6-ketoprostaglandin F1 alpha and thromboxane B2 concentrations, confirming inhibition of cyclooxygenase acti...
Van Hoogmoed L, Rakestraw PC, Snyder JR, Harmon FA.To determine the in vitro effect of various prostaglandins (PG) and nonsteroidal anti-inflammatory drugs (NSAID) on contractile activity of the large-colon taenia of horses. Methods: 14 healthy horses. Methods: The taenia was collected from the ventral colon, cut into strips (2 X 10 mm), and mounted in a tissue bath system (20-ml capacity) that contained oxygenated Krebs buffer solution warmed to 37.5+/-0.5 C. After equilibration, incremental doses of PGE2, PGF2alpha, PGl2, flunixin meglumine, carprofen, ketoprofen, and phenylbutazone were added to the baths, and contractile activity was recor...
Lanci A, Ingallinesi M, Morini M, Freccero F, Castagnetti C, Mariella J.Hydramnios is an excessive accumulation of fluid within the amniotic compartment. It is a rare condition in mares, often associated with fetal anomalies. Hydrops of fetal membranes predisposes to the rupture of the prepubic tendon, and many authors suggest the induction of parturition to preserve mare's reproductive career. This report presents the case of a 15-year-old multiparous Quarter Horse mare, referred at 268 days of gestation for suspected hydrops. Repeated ultrasonographic exams confirmed an increase in the depth of the amniotic fluid and reduced fetal viability. During the hospitali...
Janett F, Aebi L, Burger D, Imboden I, Hässig M, Kindahl H, Thun R.The objective of this study was to evaluate the effect of the non-steroidal anti-inflammatory drug (NSAID) vedaprofen (Quadrisol) on quality and freezability of stallion semen. Experiments were performed using 22 Franches Montagnes stallions from the National Stud in Avenches (Switzerland) randomly divided into a control and test group. Vedaprofen was given orally to all stallions of the test group at the recommended therapeutic dose (initial dose of 2mg/kg followed by 1mg/kg body weight every 12h) for 14 days. Control animals received the same amount of carrier substance. During treatment, bl...
Spier SJ, Meagher DM.Rational perioperative management improves the success rate of abdominal surgery. Important aspects of management are discussed, including principles of fluid therapy, nutrition, intravenous catheterization, antimicrobial prophylaxis, and the use of nonsteroidal anti-inflammatory medication. Current advances in the area of immunotherapy are mentioned.
Kallings P, Persson SG, Essén-Gustavsson B.Since nonsteroidal anti-inflammatory drugs, such as flunixin, on account of their anti-inflammatory and analgesic properties, are used in both racing and equestrian sport horses, the question has been raised as to whether these drugs affect the physiological responses to exercise and thus performance potential. Objective: The aims of this investigation were to study the effects of flunixin on cardiorespiratory, metabolic and locomotor parameters in horses during intense treadmill exercise. Methods: Six Standardbred trotters underwent an incremental treadmill exercise test to fatigue, without d...
Gerdemann R, Deegen E, Kietzmann M, Venner M.In the present study the significance of eicosanoids in the development of shock in horses on the basis of ileus has been investigated using the prostanoids thromboxane B2 (TXB2) and prostaglandine E2 (PGE2) as indicators. The prostanoid synthesis inhibitor flunixin meglumine was to be examined regarding its efficacy in the effective blockade of the synthesis of these mediators within the peri-operative timeframe as well as its effects on clinical signs and laboratory parameters. 21 horses suffering from ileus and ready for surgical intervention received an intravenous flunixin dosis of 1.1 mg...
Campbell NB, Jones SL, Blikslager AT.A potential adverse effect of cyclo-oxygenase (COX) inhibitors (nonsteroidal anti-inflammatory drugs [NSAIDs]) in horses is colitis. In addition, we have previously shown an important role for COX-produced prostanoids in recovery of ischaemic-injured equine jejunum. It was hypothesised that the nonselective COX inhibitor flunixin would retard repair of bile-injured colon by preventing production of reparative prostaglandins, whereas the selective COX-2 inhibitor, etodolac would not inhibit repair as a result of continued COX-1 activity. Segments of the pelvic flexure were exposed to 1.5 mmol/l...
Knych HK, Finno CJ, Baden R, Arthur RM, McKemie DS.The in vivo metabolism and pharmacokinetics of flunixin meglumine and phenylbutazone have been extensively characterized; however, there are no published reports describing the in vitro metabolism, specifically the enzymes responsible for the biotransformation of these compounds in horses. Due to their widespread use and, therefore, increased potential for drug-drug interactions and widespread differences in drug disposition, this study aims to build on the limited current knowledge regarding P450-mediated metabolism in horses. Drugs were incubated with equine liver microsomes and a panel of r...
Delbeke FT, Baert K, De Backer P.Urinary and plasma concentrations of the nonsteroidal anti-inflammatory drug tiaprofenic acid were determined following oral and intramuscular administration of a dose of 1 g to five fasted horses. Quantitation was performed by high-performance liquid chromatography (HPLC). The limit of quantitation (LOQ) was 0.1 microg/ml and 0.5 microg/ml in 2 ml plasma and 1 ml urine, respectively. Assay precision and extraction recovery were between acceptable values. Tiaprofenic acid pharmacokinetics were described by non-compartment analysis of the data. Absorption was faster after oral administration as...
Corveleyn S, Henrist D, Remon JP, Van Der Weken G, Baeyens W, Haustraete J, Aboul-Enein HY, Sustronck B, Deprez P.Ketoprofen (KTP) is a chiral non-steroidal anti-inflammatory drug (NSAID) of the propionic acid class, approved by the FDA for the allevation of pain associated with musculoskeletal disorders in horses. The present study was designed to examine the bioavailability of ketoprofen enantiomers after rectal administration of the racemate to healthy horses. One gram of racemic ketoprofen was injected intravenously and administered rectally as a fat based suppository in a cross-over design study (n = 4). Blood samples were analysed for KTP enantiomers using HPLC. After IV administration, the S(+) ena...
Doherty TJ, Andrews FM, Blackford JT, Rohrbach BW, Sandin A, Saxton AM.Endotoxaemia causes a disruption of gastrointestinal motility in the horse but there is no information on its effects on gastric secretion. Lipopolysaccharide (LPS) administration is known to affect gastric secretion in other species. Objective: That LPS, a toxic component of Gram-negative bacteria, would reduce gastric acid secretion and that pretreatment with phenylbutazone (PBZ) would block the effects of LPS. Methods: The effects of LPS and PBZ on gastric contents were investigated in fasted, mature horses, with permanent gastric cannulae. Horses were pretreated with either saline or PBZ 1...
Cox S, Yarbrough J.A new method of analysis has been developed and validated for the determination of firocoxib, a new nonsteroidal anti-inflammatory drug (NSAID) approved for use in horses and dogs to control pain and inflammation associated with osteoarthritis. Following a liquid extraction using ethyl acetate:hexane (40:60), samples were separated by isocratic reversed-phase HPLC on a Sunfire C(18) column and quantified using UV detection at 290 nm. The mobile phase was a mixture of water with 0.025% trifluoroacetic acid and acetonitrile, with a flow-rate of 1.1 ml/min. The procedure produced a linear curve o...
Van Eenoo P, Delbeke FT, Roels K, Baert K.Non-steroidal anti-inflammatory drugs (NSAIDs) are prohibited by the International Federation of Horse Racing Authorities but are commonly used in veterinary practice. Plasma and urinary concentrations of the NSAID tolmetin were determined by a high-performance liquid chromatographic procedure with UV detection following oral administration of a dose of 1 g to six fasted untrained standard bred mares. With a limit of quantitation (LOQ) of 0.05 microg/ml tolmetin was present in plasma for 9-12 h post-administration. Maximum concentrations of 2.1+/-0.89 microg/ml were found after 0.7+/-0.25 h. T...
Kim Y, Seo C, Oh S, Kwak J, Jung S, Sin E, Kim H, Ji M, Lee HS, Park HJ, Lee G, Yu J, Kim M, Lee W, Paik MJ.Loxoprofen is a non-steroidal anti-inflammatory drug of the 2-arylpropionic acid type, which has used to treat musculoskeletal disorders in the horse racing industry. However, it has also used illicitly to mask clinical signs of inflammation and pain in racehorses. Thus, its accurate analysis has become an important issue in horse doping laboratories. In this study, an analytical method of loxoprofen was developed as tert-butyldimethylsilyl (TBDMS) derivative by gas chromatography-mass spectrometry (GC-MS). Characteristic fragment ions of [M-15], [M-57], and [M-139] permitted the accurate and ...
Christensen JM, Blythe LL, Craig AM.Phenylbutazone was administered to six Thoroughbred horses in a cross-over study in which the horses received cimetidine pretreatment or no cimetidine pretreatment. Blood samples were collected at various times for 48 h after phenylbutazone administration and the plasma was analysed for phenylbutazone. Cimetidine pretreatment elevated phenylbutazone plasma concentrations during the first 8 h after phenylbutazone administration. The absorption rate, maximum phenylbutazone plasma concentrations and AUC were significantly greater with cimetidine pretreatment. The half-life of phenylbutazone did n...
Woods WE, Chay S, Houston T, Blake JW, Tobin T.The efficacy of testing for illegal drugs in race horses was surveyed by evaluating 27 questionnaires received from 28 racing jurisdictions polled. Large variations in the number of samples tested and drugs detected were reported. Some jurisdictions reported only illegal medications, whereas others also reported permitted medications. To facilitate comparison, stimulants, depressants, local anesthetics, narcotic analgesics, and tranquilizers were classified as hard drugs. Other drugs, which are legal in some jurisdictions, were classified as soft. To evaluate the efficacy of testing, positive ...
Hondalus MK, Lofstedt J.A 16-year-old pony with signs of intermittent abdominal pain was treated with phenylbutazone in excess of the recommended dosage. Endoscopy revealed ulceration of the esophagus, stomach, and proximal portion of small intestine. The pony developed diarrhea. Salmonella typhimurium was isolated from the blood and feces. Treatment included fluids, trimethoprim-sulfadiazine, sucralfate, and ranitidine hydrochloride. The diarrhea resolved, as did the gastrointestinal ulceration. This case was unusual because septicemia with salmonellosis is an uncommon finding in adult equids. Also, complications co...
Hunt JP, Haywood PE, Moss MS.A gas chromatographic screening procedure for the non-steroidal anti-inflammatory group of drugs is described. The method invovles on-column methylation of the carboxylic acid group using trimethylanilinium hydroxide as the methylating reagent. Fifteen such drugs were studied. Eight of these were detected in urine collected from horses that had received these compounds orally and for these drugs, rates of urinary excretion are recorded. Seven other members of this group of drugs were shown to be detectable by this procedure but in these cases the drug was added to urine and not administered to...
