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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.
Renal medullary rim sign in 2 adult quarter horses.
The Canadian veterinary journal = La revue veterinaire canadienne    October 28, 1998   Volume 39, Issue 10 647-649 
Ramirez S, Seahorn TL, Williams J.This report describes a renal ultrasonographic abnormality (medullary rim sign), which was identified in 2 separate cases of spontaneously occurring disease associated with chronic and acute overdosage of phenylbutazone therapy. In horses, medullary rim sign has only been documented in neonatal foals experimentally administered large doses of phenylbutazone.
The pharmacokinetics of furosemide in anaesthetized horses after bilateral ureteral ligation.
Journal of veterinary pharmacology and therapeutics    September 10, 1998   Volume 21, Issue 4 298-303 doi: 10.1046/j.1365-2885.1998.00142.x
Dyke TM, Hubbell JA, Grosenbaugh DA, Beard W, Mitten L, Sams RA, Hinchcliff KW.The pharmacokinetics of furosemide were investigated in anaesthetized horses with bilateral ureteral ligation (BUL) with (n = 5) or without (n = 5) premedication with phenylbutazone. Horses were administered an intravenous (i.v.) bolus dose of furosemide (1 mg/kg) approximately 60-90 min after BUL. Plasma samples collected up to 3 h after drug administration were analysed by a validated high performance liquid chromatography method. Median plasma clearance (CLp) of furosemide in anaesthetized horses with BUL was 1.4 mL/min/kg. Apparent steady state volume of distribution (Vd(ss)) ranged from 1...
Phenylbutazone prevents the endotoxin-induced delay in gastric emptying in horses. Valk N, Doherty TJ, Blackford JT, Abraha TW, Frazier DL.The effect of phenylbutazone on gastric emptying in horses was determined by measuring serum concentrations of acetaminophen. Gastric emptying was determined in normal fasted horses (n = 6), horses given endotoxin intravenously (n = 6), horses given intravenous phenylbutazone (n = 6), and horses given intravenous phenylbutazone plus endotoxin (n = 6). The mean time to reach maximum serum acetaminophen concentration (Tmax), the maximum serum concentration (Cmax), and the area under the serum acetaminophen concentration versus time curve (AUC) were compared among treatment groups. Phenylbutazone...
Pulmonary vascular pressures of strenuously exercising Thoroughbred horses after administration of phenylbutazone and frusemide.
Equine veterinary journal    April 16, 1998   Volume 30, Issue 2 158-162 doi: 10.1111/j.2042-3306.1998.tb04476.x
Manohar M, Goetz TE, Sullivan E, Griffin R.The present study was carried out to examine the effects of phenylbutazone treatment on the pulmonary haemodynamic effects of frusemide in strenuously exercising horses. Using catheter mounted manometers, whose in vivo signals were referenced at the point of the shoulder, heart rate, right atrial, right ventricular and pulmonary vascular pressures were measured in 3 different sets of experiments. Seven Thoroughbreds were subjected to 1) control (no medications), 2) frusemide control and 3) phenylbutazone + frusemide. The experiments were carried out in random order and were separated by 7 days...
Duration of effects of phenylbutazone on serum total thyroxine and free thyroxine concentrations in horses.
Journal of veterinary internal medicine    February 21, 1998   Volume 11, Issue 6 371-374 doi: 10.1111/j.1939-1676.1997.tb00483.x
Ramirez S, Wolfsheimer KJ, Moore RM, Mora F, Bueno AC, Mirza T.The objectives of this study were to determine if phenylbutazone decreased serum thyroxine (TT4) and free thyroxine (FT4) concentrations using radioimmunoassay and equilibrium dialysis techniques in horses, and, if so, an additional objective was to determine the duration of this decreased concentration once phenylbutazone administration was discontinued. Serum TT4 and FT4 concentrations were determined before and after administration of 4.4 mg/kg of phenylbutazone i.v. bid for 5 days. Treatment with phenylbutazone caused a significant decrease in TT4 and FT4 concentrations (P < .05). Serum...
Uptake of drugs from topically applied anti-inflammatory preparations applied to racing animals.
Australian veterinary journal    February 20, 1998   Volume 75, Issue 12 897-901 doi: 10.1111/j.1751-0813.1997.tb11261.x
Thomas AD, Bowater IC, Vine JH, McLean JG.To determine whether a drug detected in the blood or urine of a racing animal could have penetrated through the skin from a topically applied preparation. Methods: Blood and urine of dogs and horses were analysed after topical administration of three common nonsteroidal anti-inflammatory preparations. Methods: Dimethylsulphoxide was analysed using a gas chromatograph with a flame photometric detector. Phenylbutazone, its metabolites and lignocaine were analysed using a gas chromatograph with a mass selective detector. Results: Dimethylsulphoxide, phenylbutazone and lignocaine were detected in ...
Treatment of horses with phenylbutazone.
The Veterinary record    January 10, 1998   Volume 141, Issue 22 584 
Dyson S.No abstract available
Pharmacokinetics of intravenous and intragastric cimetidine in horses. I. Effects of intravenous cimetidine on pharmacokinetics of intravenous phenylbutazone.
Journal of veterinary pharmacology and therapeutics    November 14, 1997   Volume 20, Issue 5 355-361 doi: 10.1046/j.1365-2885.1997.00083.x
Sams RA, Gerken DF, Dyke TM, Reed SM, Ashcraft SM.Cimetidine was administered intravenously and by the intragastric route to six mares at a dose of 4.0 mg/kg of body weight (bw). Specific and sensitive high performance liquid chromatographic methods for the determination of cimetidine in horse plasma and urine and cimetidine sulfoxide in urine are described. Plasma cimetidine concentration vs. time data were analysed by non-linear least squares regression analysis to determine pharmacokinetic parameter estimates. The median (range) plasma clearance (Cl) was 8.20 (4.96-10.2) mL/min.kg of body weight, that of the steady-state volume of distribu...
The effect of the acute-phase response on in vitro drug metabolism and plasma protein binding in the horse.
Veterinary research communications    July 1, 1997   Volume 21, Issue 5 361-368 doi: 10.1023/a:1005816422279
Mills PC, Ng JC, Auer DE.The effect of the acute-phase response (APR) on the activity of the hepatic drug-metabolizing system (DMS) and on the binding of phenylbutazone to plasma proteins was investigated in the horse. An APR was induced by intramuscular injections of Freund's complete adjuvant in five horses and, five days later, these horses together with five clinically normal horses were shot and the right ventral lobe of each liver removed. The hepatic microsomal fractions from the liver samples were isolated and significantly lower (p < 0.01) concentrations of cytochromes P450 and b5 and activities of aniline...
Treatment of a keratoma in a Clydesdale horse.
The Veterinary record    April 26, 1997   Volume 140, Issue 17 453-456 doi: 10.1136/vr.140.17.453
Chan CC, Munroe GA.A keratoma was diagnosed in a six-year-old Clydesdale gelding with recurrent 'pus in the foot'. The keratoma was excised through an inverted 'V' dorsal wall hoof resection up to 2 cm distal to the coronary band, the foot was bandaged and shod, and the horse treated with antibiotics and phenylbutazone. The dorsal hoof wall regrew completely and the horse gradually returned to full work.
Preliminary investigations of pain and analgesia assessment in horses administered phenylbutazone or placebo after arthroscopic surgery.
Veterinary surgery : VS    March 1, 1997   Volume 26, Issue 2 150-155 doi: 10.1111/j.1532-950x.1997.tb01478.x
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...
Comparative pharmacokinetics of phenylbutazone and its metabolite oxyphenbutazone in clinically normal horses and donkeys.
American journal of veterinary research    January 1, 1997   Volume 58, Issue 1 53-55 
Mealey KL, Matthews NS, Peck KE, Ray AC, Taylor TS.To compare plasma disposition of phenylbutazone and its metabolite oxyphenbutazone after i.v. administration of phenylbutazone in horses and donkeys. Methods: 4 clinically normal horses and 6 clinically normal donkeys. Methods: Blood samples were collected from each animal at time 0 (before) and 5, 10, 20, 30, 45, 60, 90, 120, 180, 240, 300, 360, and 480 minutes after i.v. administration of a bolus dose of phenylbutazone. Serum was analyzed in triplicate by use of high-performance liquid chromatography for determination of phenylbutazone and oxyphenbutazone concentrations. The serum concentrat...
The effect of inflammation on the disposition of phenylbutazone in thoroughbred horses.
Journal of veterinary pharmacology and therapeutics    December 1, 1996   Volume 19, Issue 6 475-481 doi: 10.1111/j.1365-2885.1996.tb00085.x
Mills PC, Ng JC, Auer DE.The effect of inflammation on the disposition of phenylbutazone (PBZ) was investigated in Thoroughbred horses. An initial study (n = 5) in which PBZ (8.8 mg/kg) was injected intravenously twice, 5 weeks apart, suggested that the administration of PBZ would not affect the plasma kinetics of a subsequent dose. Two other groups of horses were given PBZ at either 8.8 mg/kg (n = 5) or 4.4 mg/kg (n = 4). Soft tissue inflammation was then induced by the injection of Freud's adjuvant and the administration of PBZ was repeated at a dose level equivalent to, but five weeks later than, the initial dose. ...
Pharmacokinetic interactions between repeated dose phenylbutazone and gentamicin in the horse.
Journal of veterinary pharmacology and therapeutics    December 1, 1996   Volume 19, Issue 6 454-459 doi: 10.1111/j.1365-2885.1996.tb00082.x
Whittem T, Firth EC, Hodge H, Turner K.This study examined the pharmacokinetics of steady-state phenylbutazone and single bolus intravenous gentamicin when administered together in the horse. The trial design was completed as a cross-over with seven thoroughbred horses. In the first phase each horse received 2.2 mg/kg gentamicin intravenously. After a 2-week washout, each horse received 4.4 mg/kg phenylbutazone intravenously every 24 h for 5 days. On the fourth day each horse received gentamicin as before. Plasma was harvested for gentamicin concentration determination by fluorescence polarization immunoassay and for phenylbutazone...
Atypical villonodular synovitis in a horse.
Journal of the American Veterinary Medical Association    November 1, 1996   Volume 209, Issue 9 1602-1603 
Vickers KL, Ross MW.A 4-year-old sexually intact male Standardbred trotter was evaluated for left forelimb lameness. A presumptive diagnosis of severe cartilage damage was made because the horse had a history of infectious arthritis involving the left metacarpophalangeal joint. Arthroscopic evaluation revealed what was presumed to be a large villonodular lesion. The mass was surgically removed, and the horse was treated with procaine penicillin G, trimethoprim-sulfamethoxazole, phenylbutazone, and polysulfated glycosaminoglycans and eventually returned to racing. Histologic examination of the mass revealed a bed ...
Quantification of phenylbutazone in equine sera by use of high-performance liquid chromatography with a nonevaporative extraction technique.
American journal of veterinary research    November 1, 1996   Volume 57, Issue 11 1522-1524 
Peck KE, Ray AC, Manuel G, Rao MM, Foos J.To develop a sensitive, rugged high-performance liquid chromatography (HPLC) method for the measurement of phenylbutazone (PBZ) in equine sera, using a rapid, nonevaporative extraction technique. Methods: Sera from 5 nonexercising adult horses. Methods: After addition of sodium chloride and acetonitrile to serum samples, reverse-phase HPLC analysis for PBZ and oxyphenbutazone (OXY) was performed directly on extracts, using diode array UV spectrophotometric detection. Probenecid was used as an internal standard. Data were evaluated by standard means of statistical analysis. Results: Recoveries ...
Pulmonary vascular pressures of strenuously exercising thoroughbreds after administration of phenylbutazone.
American journal of veterinary research    September 1, 1996   Volume 57, Issue 9 1354-1358 
Manohar M, Goetz TE, Griffin R, Sullivan E.To determine the effects of phenylbutazone administration on heart rate and right atrial and pulmonary vascular pressures in Thoroughbreds during rest and during exercise performed at maximal heart rate. Methods: 7 healthy, exercise-conditioned Thoroughbreds. Methods: Horses were studied on 3 occasions: without medication [control], after i.v. administration of phenylbutazone (4.4 mg/kg of body weight) at 12-hour intervals for 2 days and a final dose given 1 hour before exercise, and after i.v. administration of phenylbutazone for 2 days in the same manner, but with the final dose given 24 hou...
Phenylbutazone increases right atrial pressure and heart rate of running horses.
Journal of applied physiology (Bethesda, Md. : 1985)    July 1, 1996   Volume 81, Issue 1 312-317 doi: 10.1152/jappl.1996.81.1.312
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...
Effects of pretreatment with ketoprofen and phenylbutazone on experimentally induced synovitis in horses.
American journal of veterinary research    June 1, 1996   Volume 57, Issue 6 866-874 
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,...
[The concentration changes of different phenylbutazone formulations in horse plasma].
DTW. Deutsche tierarztliche Wochenschrift    June 1, 1996   Volume 103, Issue 6 224-230 
Keller H, Hashem A.In a study in the horse, the disposition, the pharmacokinetic parameters and the absorption rates of 3 formulations of phenylbutazone (injection solution, powder and paste suspension) have been determined. After i.v. injection, the half-life time of phenylbutazone has been determined to be 6.6-6.7 h. After oral administration, the absorption of phenylbutazone was found to be faster after administration via stomach tube than after direct application into the mouth. The absorption rat constant of the paste suspension was found to be higher than that of the powder (1.797-2.304 h-1 vs. 0.656-1.197...
Determination of phenylbutazone and oxyphenbutazone in plasma and urine samples of horses by high-performance liquid chromatography and gas chromatography-mass spectrometry.
Journal of chromatography. B, Biomedical applications    April 12, 1996   Volume 678, Issue 2 211-218 doi: 10.1016/0378-4347(95)00508-0
Neto LM, Andraus MH, Salvadori MC.A method is described for the qualitative and quantitative determination of phenylbutazone and oxyphenbutazone in horse urine and plasma samples viewing antidoping control. A horse was administered intravenously with 3 g of phenylbutazone. For the qualitative determination, a screening by HPLC was performed after acidic extraction of the urine samples and the confirmation process was realized by GC-MS. Using the proposed method it was possible to detect phenylbutazone and oxyphenbutazone in urine for up to 48 and 120 h, respectively. For the quantitation of these drugs the plasma was deprotein...
Ultrasonographic renal changes associated with phenylbutazone administration in three foals.
The Canadian veterinary journal = La revue veterinaire canadienne    April 1, 1996   Volume 37, Issue 4 235-236 
Léveillé R, Miyabayashi T, Weisbrode SE, Biller DS, Takiguchi M, Williams JF.No abstract available
The dose-related effects of phenylbutazone and a methylprednisolone acetate formulation (Depo-Medrol) on cultured explants of equine carpal articular cartilage.
Journal of veterinary pharmacology and therapeutics    December 1, 1995   Volume 18, Issue 6 429-437 doi: 10.1111/j.1365-2885.1995.tb00621.x
Jolly WT, Whittem T, Jolly AC, Firth EC.The dose-related effects of phenylbutazone and Depo-Medrol on chondrocyte viability and chondrocyte-mediated synthesis and depletion of proteoglycans were investigated using cultured explants of equine middle carpal joint articular cartilage. Explants from 12 horses (941 x 3 mm diameter) were cultured for a total of 5 days, which included 3 days' exposure to either phenylbutazone (0, 2, 20, 200 or 2000 micrograms/mL) or Depo-Medrol (0, 20, 200 or 2000 micrograms/mL). For each explant, amino sugar content was used as a measure of proteoglycan content, 35S incorporation as a measure of the rate ...
Pharmacologic interaction of furosemide and phenylbutazone in horses.
American journal of veterinary research    September 1, 1995   Volume 56, Issue 9 1206-1212 
Hinchcliff KW, McKeever KH, Muir WW, Sams RA.The effect of premedication with phenylbutazone on systemic hemodynamic and diuretic effects of furosemide was examined in 6 healthy, conscious, mares. Mares were instrumented for measurement of systemic hemodynamics, including cardiac output and pulmonary arterial, systemic arterial, and intracardiac pressures, and urine flow. Each of 3 treatments was administered in a randomized, blinded study; furosemide (1 mg/kg of body weight, IV) only, phenylbutazone (8.8 mg/kg, PO, at 24 hours and 4.4 mg/kg, IV, 30 minutes before furosemide) and furosemide, or 0.9% NaCl. Phenylbutazone administration si...
Infectious tenosynovitis.
The Veterinary clinics of North America. Equine practice    August 1, 1995   Volume 11, Issue 2 163-176 doi: 10.1016/s0749-0739(17)30318-8
Bertone AL.Infectious tenosynovitis is treated similarly to infectious arthritis. The principles of treatment include an early diagnosis and immediate therapy. Therapy should include use of systemic and local antimicrobials and sheath lavage and drainage. Fibrosis and adhesions can be minimized with passive range of motion exercises, intrathecal hyaluronate, and phenylbutazone therapy. Restrictive fibrosis may be treated successfully by annular ligament resection.
Effects of ketoprofen and phenylbutazone on chronic hoof pain and lameness in the horse.
Equine veterinary journal    July 1, 1995   Volume 27, Issue 4 296-300 doi: 10.1111/j.2042-3306.1995.tb03080.x
Owens JG, Kamerling SG, Stanton SR, Keowen ML.The analgesic effects of the nonsteroidal anti-inflammatory drugs, ketoprofen (2.2 and 3.63 mg/kg bwt) and phenylbutazone (4.4 mg/kg bwt) were compared in 7 horses with chronic laminitis. Hoof pain was quantified objectively by means of an electronic hoof tester and lameness was subjectively graded on a modified Obel scale. Ketoprofen at a dose of 3.63 mg/kg bwt (phenylbutazone equimolar dose) reduced hoof pain and lameness to a greater extent than the 2.2 mg/kg dose and phenylbutazone. These effects were still present at 24 h in 3 of the 4 pain tests, including lameness grade. These data sugg...
Medical management of right dorsal colitis in 5 horses: a retrospective study (1987-1993).
Journal of veterinary internal medicine    July 1, 1995   Volume 9, Issue 4 272-276 doi: 10.1111/j.1939-1676.1995.tb01079.x
Cohen ND, Carter GK, Mealey RH, Taylor TS.Right dorsal colitis in horses has been associated with administration of phenylbutazone. Although reports of right dorsal colitis in this species have described surgical treatment associated with a poor prognosis, we have had success treating this condition medically. This report describes 5 horses with right dorsal colitis confirmed during celiotomy that were initially managed medically. All horses had a history of intermittent abdominal pain; weight loss was noted in only 1 horse. The doses (2.0 to 4.6 mg/kg PO bid) and duration (5 to 30 days) of administration of phenylbutazone were not un...
A non-invasive and quantitative method for the study of tissue injury caused by intramuscular injection of drugs in horses.
Journal of veterinary pharmacology and therapeutics    June 1, 1995   Volume 18, Issue 3 226-235 doi: 10.1111/j.1365-2885.1995.tb00583.x
Toutain PL, Lassourd V, Costes G, Alvinerie M, Bret L, Lefebvre HP, Braun JP.The present study was undertaken to measure the weight of muscle destroyed by an intramuscular injection of phenylbutazone (PBZ) in horses. In six horses, CK disposition parameters were evaluated after intravenous (i.v.) and intramuscular (i.m.) administration of a CK horse preparation. The same horses received PBZ, a potentially irritating agent, by i.v. and i.m. (neck and hindquarter) routes. Data were analysed using compartmental approaches and instantaneous CK flux was calculated using a discrete deconvolution method. For a 150 U/kg CK dose, the steady-state volume of distribution was 0.05...
Plasma concentrations and therapeutic efficacy of phenylbutazone and flunixin meglumine in the horse: pharmacokinetic/pharmacodynamic modelling.
Journal of veterinary pharmacology and therapeutics    December 1, 1994   Volume 17, Issue 6 459-469 doi: 10.1111/j.1365-2885.1994.tb00278.x
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...
Multifocal myositis associated with Sarcocystis sp in a horse.
Journal of the American Veterinary Medical Association    December 1, 1994   Volume 205, Issue 11 1574-1576 
Traub-Dargatz JL, Schlipf JW, Granstrom DE, Ingram JT, Shelton GD, Getzy DM, Lappin MR, Baker DC.Multifocal myositis was diagnosed in a 7-year-old Quarter Horse gelding on the basis of history and findings on physical examination, serum biochemical analysis, electromyography, and microscopic examination of frozen sections of muscle biopsy specimens. Histologic examination of the muscle specimen revealed multifocal accumulations of histiocytes, lymphocytes, and plasma cells, with attendant myofiber degeneration and necrosis. Parasitic cysts with morphologic characteristics of Sarcocystis sp were found in regions of myocyte degeneration and necrosis, and in regions of normal muscle. Based o...
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