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Topic:Phenylbutazone
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.
Phenylbutazone and oxyphenbutazone distribution into tissue fluids in the horse. The clinically recommended dose rate of phenylbutazone (4.4 mg/kg) was administered intravenously as a single dose to five Welsh Mountain ponies. Distribution of phenylbutazone and its active metabolite oxyphenbutazone into body fluids was studied by measuring concentrations in plasma, tissue-cage fluid, peritoneal fluid and acute inflammatory exudate harvested from a polyester sponge model of inflammation. The ready penetration of phenylbutazone into inflammatory exudate was demonstrated by the relatively high mean value for Cmax of 12.4 micrograms/ml occurring at a time of 4.6 h and a mean A...
Effects of flunixin meglumine, phenylbutazone and a selective thromboxane synthetase inhibitor (UK-38,485) on thromboxane and prostacyclin production in healthy horses. 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...
Phenylbutazone in the horse: a review. 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...
Absorption and pharmacokinetics of phenylbutazone in Welsh Mountain ponies. The disposition of phenylbutazone (4.4 mg/kg), administered intravenously to six Welsh Mountain ponies, was described by a two-compartment open model. Pharmacokinetic parameters were not significantly different after morning dosing in comparison with afternoon dosing. When phenylbutazone (4.4 mg/kg) was administered orally to the same ponies, marked variations in time to peak concentrations were produced with different feeding schedules. When access to hay was permitted before and after dosing, the mean time to peak concentration was 13.2 +/- 1.2 h and double peaks in the plasma concentration-...
Modulation of arachidonic acid metabolism in endotoxic horses: comparison of flunixin meglumine, phenylbutazone, and a selective thromboxane synthetase inhibitor. 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...
Effects of oral cimetidine on plasma concentrations of phenylbutazone in horses. 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...
Efficacy of testing for illegal medication in horses. 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 ...
Inhibitory effects of intravenous chloramphenicol sodium succinate on the disposition of phenylbutazone in horses. The effects of i.v. chloramphenicol sodium succinate on the pharmacokinetics of i.v. phenylbutazone in six healthy adult horses were investigated. Administration of chloramphenicol sodium succinate to mares reduced mean (+/- SD) phenylbutazone clearance from 0.600 +/- 0.222 to 0.339 +/- 0.123 ml/min per kg and increased mean (+/- SD) half life from 244 +/- 59.8 to 371 +/- 80.8 min and mean residence time from 333 +/- 86.2 to 533 +/- 124 min. The mean steady-state volume of distribution of phenylbutazone was unchanged, with mean (+/- SD) values of 187 +/- 28.9 ml/kg in control animals and 170 +...
[An undesirable drug interaction in horses? Complications which can occur during the administration of coumarin derivatives and phenylbutazone]. A study of the literature was done because of questions asked in a court of justice concerning possible poisoning in a jumper, resulting from administration of both phenylbutazone and a coumarin derivative within a particular period. In view of the mechanisms of action and the pharmacokinetic characteristics of the agents, these forms of combined treatment are also highly inadvisable in horses.
Experimentally induced phenylbutazone toxicosis in ponies: description of the syndrome and its prevention with synthetic prostaglandin E2. Phenylbutazone (PBZ) toxicosis was induced in 9 ponies to further define the clinical and pathologic changes occurring with this syndrome. Six additional ponies were treated with PBZ and a synthetic prostaglandin E2 to determine the role of prostaglandins in the pathogenesis of PBZ toxicosis. Ponies given only PBZ exhibited CNS depression, anorexia, weight loss, diarrhea, cyanotic mucous membranes, and oral ulcers. Total serum protein concentration gradually decreased during the 10-day treatment period. Marked mucosal atrophy, focal erosions, and ulcers characterized the lesions in the aliment...
Effect of diuresis on urinary excretion and creatinine clearance in the horse. Endogenous creatinine clearance and renal excretion of phenylbutazone, osmotically active material, and compounds contributing to the urinary refractive index were studied in 12 Thoroughbred mares after no treatment, after water administration, or after furosemide administration. Urine was quantitatively collected, using urinary bladder catheters. On average, urine flow of the mares was 9 microliters/min/kg without treatment and increased to about 50 microliters/min/kg after water administration and to about 70 microliters/min/kg after furosemide administration. Water administration increased ...
Phenylbutazone and its metabolites in plasma and urine of thoroughbred horses: population distributions and effects of urinary pH. A survey of plasma and urinary concentrations of phenylbutazone and its metabolites in thoroughbred horses racing in Kentucky was carried out. Post-race blood samples from more than 200 horses running at Latonia Racetrack and Keeneland in the Spring of 1983 were analysed. The modal plasma concentration of phenylbutazone was between 1 and 2 micrograms/ml, the mean concentration was 3.5 micrograms/ml and the range was up to 15 micrograms/ml. Oxyphenbutazone had a modal plasma concentration between 1 and 2 micrograms/ml, a mean concentration of 2.07 micrograms/ml and a range of up to 13 microgram...
Effects of phenylbutazone and oxyphenbutazone on basic drug detection in high performance thin layer chromatographic systems. 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...
Estimation of urine flow rate in mares. To determine the rate of urine flow and thus urinary excretion in the horse from untimed urine samples alone, the flow rate, creatinine concentration, osmolarity, and refractive index of 228 quantitatively collected urine samples were determined in 53 experiments on 12 healthy Thoroughbred mares. Forty samples were collected after water-induced diuresis; 11 samples were collected after furosemide-induced diuresis. Flow rates, which ranged from 1.2 to 84.5 ml/min, could be predicted from the urinary creatinine concentration. Correlation of urinary flow with urinary creatinine concentration acco...
Plasma and serum concentrations of phenylbutazone and oxyphenbutazone in racing Thoroughbreds 24 hours after treatment with various dosage regimens. The plasma and serum concentrations of phenylbutazone (PBZ) and oxyphenbutazone were measured in 158 Thoroughbred horses after various doses of PBZ wer given. All horses were competing or training at racetracks in various parts of the country. All horses used in the study had not been given PBZ 24 hours before they were placed on a specific dosage schedule. Samples were collected 24 hours after the last PBZ administration. Four grams of PBZ were given daily by stomach tube, paste, or tablet for 3 days. On day 4, 24 hours before sample collection, an IV dose of 2 g of PBZ was given, regardless ...
Pharmacokinetics of phenylbutazone in two age groups of ponies: a preliminary study. A clinical dose rate (4.4 mg/kg bodyweight) of phenylbutazone was administered intravenously and orally to six Welsh mountain ponies to provide data on the pharmacokinetics and bioavailability of the drug. In three, three-year-old ponies, clearance of the drug from plasma after intravenous administration was almost twice as rapid as in three ponies aged eight to 10 years. After oral administration, plasma phenylbutazone levels were greater in the older ponies, the area under the plasma concentration time curve being almost twice as high. This did not result from more efficient absorption but f...
Clinical pharmacology and therapeutic uses of non-steroidal anti-inflammatory drugs in the horse. 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...
Effects of phenylbutazone and anabolic steroids on adrenal and thyroid gland function tests in healthy horses. Adrenal and/or thyroid gland function tests were evaluated in horses at various times during short-term therapy with phenylbutazone, stanozolol, and boldenone undecylenate. There were no significant treatment or time effects on mean basal plasma cortisol concentrations in horses during treatment with the following: phenylbutazone, given twice daily (4 to 5 mg/kg, IV) for 5 days; stanozolol, given twice weekly (0.55 mg/kg, IM) for 12 days; boldenone undecylenate, given twice weekly (1.1 mg/kg, IM) for 12 days; or nothing. There was no significant effect of phenylbutazone treatment on the change...
[Chronopharmacokinetics of phenylbutazone in the horse. Application to antidoping control]. Chronopharmacokinetics of intravenous phenylbutazone in the horse was studied with the aim of antidoping control. Among parameters studied, the single one which seemed to depend on circadian rhythm was the elapsed time between the injection and the plasmatic peak. There was no relationship between the injection time and the both parameters: half-life and time required to reach the forensic level of 4 micrograms/ml. This later, and oxyphenbutazone/phenylbutazone ratio, should depend on individual factors. Therefore, the injection time should not be a main parameter for the phenylbutazone evalua...
Differential effects of phenylbutazone and local anesthetics on nociception in the equine. The effects of procaine, mepivacaine and phenylbutazone on pain perception in the equine were studied using two behavioral assays of nociception; the thermal evoked hoof withdrawal reflex and skin twitch reflex. Pain perception threshold was measured as the latency from onset of thermal stimuli to reflex withdrawal of the forelimb or contraction of the cutaneous musculature. Procaine 2% and mepivacaine 2% prolonged the hoof withdrawal reflex latency when administered locally by producing a block of the palmar and metacarpal nerves. Significant analgesia lasted 90 min and 210 min for procaine a...
Effect of feeding on the fate of orally administered phenylbutazone, trimethoprim and sulphadiazine in the horse. Phenylbutazone, sulphadiazine and trimethoprim were administered to three horses on two occasions, recently fed and unfed, and the effect of feeding on the pharmacokinetics of the three drugs assessed. The mean peak concentrations of phenylbutazone and trimethoprim were reduced by feeding by 34 and 75 per cent, respectively. The pharmacokinetics of sulphadiazine were not significantly affected.
Population distributions of phenylbutazone and oxyphenbutazone after oral and i.v. dosing in horses. Experiments to determine the residual plasma concentrations of phenylbutazone and its metabolites found in horses racing on a 'no-race day medication' or 24-h rule were carried out. One dosing schedule (oral-i.v.) consisted of 8.8 mg/kg (4 g/1000 lbs) orally for 3 days, followed by 4.4 mg/kg (2 g/1000 lbs) intravenously on day 4. A second schedule consisted of 4.4 mg/kg i.v. for 4 days. The experiments were carried out in Thoroughbred and Standardbred horses at pasture, half-bred horses at pasture, and in Thoroughbred horses in training. After administering the i.v. schedule for 4 days to Thor...
Vascular pathology in phenylbutazone intoxicated horses. Three mature Thoroughbred geldings were given 13.63 mg phenylbutazone/Kg bodyweight intravenously for 3 days and repeated in one horse 4 days later. After 4, 7 and 10 days (double treatment), degeneration of the wall of small veins occurred in all horses. The veins were dilated and/or showed hyalin degeneration. The phlebopathy was interpreted to be paramount in phenylbutazone intoxication. All other manifestations, including erythro- and leukodiapedesis, submucosal edema and ulceration of the gastrointestinal mucosa, phlebothrombosis and significant changes in the hemogram and serum chemistry...
Influence of phenylbutazone on eicosanoid levels in equine acute inflammatory exudate. 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...
Serum concentration of penicillin in the horse after repeated intramuscular injections of procaine penicillin G alone or in combination with benzathine penicillin and/or phenylbutazone. Twenty-one adult horses were randomly assigned into 7 groups of 3 and were treated for 5 days with procaine penicillin G, benzathine penicillin , or phenylbutazone in various combinations and dosage schedules. Serum concentration of penicillin was measured serially over a 7-day period. The highest mean peak serum concentration was 2.06 micrograms/ml. Comparable peak values were seen 2 to 4 hours after administration of 22,000 IU of procaine penicillin G/kg of body weight given once or twice daily. A minimum serum concentration of 0.25 micrograms/ml was selected as adequate for efficacy against...
The acute inflammatory process, arachidonic acid metabolism and the mode of action of anti-inflammatory drugs. 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...
Phenylbutazone toxicosis in the horse: a clinical study. 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...
Effects of toxic doses of phenylbutazone in ponies. Toxic doses of phenylbutazone (10 mg/kg of body weight) were administered to 10 ponies once daily for 14 days. Clinical signs of toxicosis similar to those seen in other species included CNS depression, anorexia, oral ulcers, and soft feces. Six ponies died in 7 to 20 days; 1 pony was euthanatized during an acute abdominal crisis; and 3 ponies survived the study. At necropsy, the major lesions were oral and gastrointestinal ulcerations and renal changes.
