Chemicals / Complex Chemical Agents/ Chemical:
Phenylbutazone (with special reference to Ruminants and Elephants)

INFORMATION AVAILABLE

GENERAL CHEMICAL INFORMATION THERAPEUTIC INFORMATION [DOSE, FREQUENCY & ROUTE]

NUTRITIONAL INFORMATION

TOXICITY INFORMATION ENVIRONMENTAL INFORMATION
Information in this page has been entered to support the current volumes of Wildpro and further information will be added as new volumes are completed. This page is not intended to substitute for the manufacturer's data sheet and the information is not yet complete for all species, or for all contra-indications etc.

CAUTION: Before any pharmaceutical product is used, the manufacturer's data sheet, containing information on uses, dosage and administration, contra-indications, warnings etc., should always be consulted. It is important to remember that licensing of pharmaceutical products for use in a particular species/condition, as well as mandatory meat and milk withdrawal times for food-producing animals, varies between countries and changes with time. Withdrawal times also may vary between different pharmaceutical formulations and depending on route of administration. In the EU, the prescription cascade must be followed (see LCofC1.2H and W564.Apr05.w1); note that specific restrictions apply for food-producing animals. In the USA, FARAD may be consulted regarding residues and meat and milk withdrawal times.

General Chemical Information

Summary 
A non-steroidal anti-inflammatory drug (NSAID) commonly used for the treatment of musculoskeletal disorders in horses. Effective in ruminants but generally prohibited for use in food-producing animals due to risks of residues causing rare but potentially fatal side-effects in humans.

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Names and Formulae
Type Synthetic pyrazolone derivative. (B263, J289.27S1.w1)
Alternative Names --
Chemical Formula 3,5-Pyrazolidinedione, 4-butyl-1,2-diphenyl- (J289.27S1.w1)

4-butyl-1,2-diphenyl-3,5-pyrazolidinedione. (J4.194.w1)

Chemical Structure --
Molecular Weight 308.37 (J289.27S1.w1)
Related Chemicals Aminopyrine. (B263)

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Physical Properties / Chemistry
Appearance

White to off-white crystalline powder, odourless, (B263, J289.27S1.w1) initially tasteless with a slightly bitter after-taste. (B263)

Melting point --
Boiling point --
Density --
Water solubility Very slightly soluble. (B263J289.27S1.w1)
Other solubility
  • Soluble in alcohol (J289.27S1.w1; solubility of 1 g in 28 mL alcohol. (B263)
  • Freely soluble in ether. (J289.27S1.w1)
  • Freely soluble in acetone. ( J289.27S1.w1)
Acid/Base
  • Strongly acidic in solution. (B322.3.w3)
  • pKa 4.5 in water. (B263J289.27S1.w1)
  • pH of aqueous solution 8.2 (J289.27S1.w1)

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Pharmacology & General Information
Pharmacology
  • "Analgesic, anti-inflammatory, antipyretic and mild uricosuric properties." (B263)
  • Proposed mechanism of action is reduction of prostaglandin synthesis by cyclooxygenase inhibition. (B263)
  • May also reduce renal blood flow, decrease glomerular filtration rate, decrease platelet aggregation and damage gastric mucosa. (B263)
  • Analgesic activity is proposed to be a centrally acting effect. (J4.194.w1)
Storage / Stability
  • Injectable products should be stored in a cool place (46-56F) or kept refrigerated; oral products should be stored in tight child-resistant containers. (B263)
Legal Category (In UK) POM (B266)

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References

Associated Techniques

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ORGANISATIONS

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ELECTRONIC LIBRARY
(Further Reading)
Click image for full contents list of ELECTRONIC LIBRARY

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Authors Debra Bourne (V.w5); Gracia Vila-Garcia (V.w67)
Referees Suzanne I. Boardman (V.w6); Susan Mikota (V.w72)

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Therapeutic Information

Uses/Indications
Activity --
Appropriate Use
  • As an anti-inflammatory agent. Mainly used in treatment of musculoskeletal inflammation such as osteoarthritis. (B322.3.w3)
  • Mainly used in treating lameness in horses, also less frequently as an analgesic/ anti-inflammatory/ antipyretic in dogs, cattle and pigs. (B263)
Limitations
  • Not suitable for intramuscular or subcutaneous injection due to the acidity of the drug in solution. (B322.3.w3)
  • May be given by slow intravenous injection however thrombophlebitis may result from administration by this route. (B322.3.w3)
Notes --

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Pharmacokinetics and Drug Interactions
Absorption /Bioavailability
  • Readily absorbed following oral administration. (B322.3.w3)
  • Absorbed from both the stomach and the small intestine. (B263)

Note: Phenylbutazone has been shown to bind to chopped hay and other feedstuffs (powdered "pony nuts"); percentage binding increased with time and decreased with concentration, but the variation with buffer pH was unpredictable. The drug was also found to bind to digesta within the gastrointestinal tract. Drug uptake and release from ingesta and digesta in equines were considered to be probably absorptive and desorptive processes. (J21.44.w2)

In cattle:

  • Systemic availability of 89% following intramuscular administration of 6 mg/kg in healthy dairy cows. [1979] (J289.2.w1)
  • Systemic availability of 68% following oral administration of 6 mg/kg in healthy dairy cows. [1979] (J289.2.w1)
  • Systemic availability in cows average 67.5% (SEM 6.3) following oral administration but with a range of 41.9-95.5%. [1980] (J289.3.w1)
  • Following repeated oral dosing of cows with 2.5 g (approximately 5 mg/kg bodyweight) twice daily for eight days, minimum plasma concentration during steady state was 100.4 +/1 7.3 g/mL plasma (mean +/- SD); this was lower than the expected value of 174 g/mL. (J289.7.w1)
  • Systemic availability in mature Holstein bulls following oral dosing with 10 mg/kg was 73% +/- 2%. (J13.51.w2)
  • In calves age 4-5 months and weighing 77-105 kg, following oral administration of 4.4 mg/kg, mean bioavailability was 66% with a range of 47-91%. (J289.25.w1)

In goats:

  • Systemic availability, following oral administration to mixed-breed adult goats at 4.4 mg/kg, of 82 +-6% (mean +/- SE) or 61 % +/-7% when corrected by the t1/2 β; relatively slow absorption with maximum drug concentration occurring at 3.47 +/- 0.39 hrs after oral administration and mean absorption time of 10.4 (+/-8.61) hours. (J3.140.w7)
Distribution

In cattle: 

  • Apparent volume of distribution 0.1 L/kg following intravenous administration of 6 mg/kg in healthy dairy cows. [1979] (J289.2.w1)
  • Apparent volume of distribution 0.09 L/kg following intravenous administration of 5 mg/kg in non-lactating non-pregnant cows. [1980] (J289.3.w1)
  • Mean apparent volume of distribution in mature Holstein bulls 0.134 +/- 0.021 L/kg. (J13.51.w2)
  • Mean apparent volume of distribution for steady-state after multiple oral dosing of mature Holstein bulls 0.201 +/- (SEM) 0.009 L/kg. (J13.51.w3)
  • In calves age 4-5 months and weighing 77-105 kg data from administration of 4.4 mg/kg, either intravenously or orally, showed an apparent volume of distribution of 0.09 L/kg. (J289.25.w1)
  • Mean volume of distribution at steady state 0.14 L/kg following intravenous administration of 6 mg/kg in beef steers 234-354 kg. (J289.25.w2)
  •  

In goats:

  • Calculated volume of distribution at steady state following intravenous administration to mixed-breed adult goats at 4.4 mg/kg, was 88.0 +/- 13.3 mL/kg (mean +/- SE). (J3.140.w7)
  • Apparent volume of distribution 0.28 L/kg. (J13.33.w1)
  • In goats following administration of phenylbutazone intravenously (10 mg/kg), distribution half-life t1/2α was 1.8 +/- 1.2 (mean +/- SEM) h in six-week-old kids and 1.5 +/- 0.6 h in adults. The volume of distribution Vd(ss) varied with age: 0.38 +/-0.02 L/kg in one-day-old kids, 0.31 +/- 0.04 in 10-day -old kids, 0.22 +/- 0.01 in four-week-old kids, 0.25 +/- 0.02 in six-week-old kids and 0.27 +/- 0.02 in adults; values for kids of all ages except six-weeks-old were significantly (P<0.05) different from the value for adults. (J289.16.w2)

In sheep:

  • Following administration of phenylbutazone at 4.4 mg/kg intravenously in male one-year-old sheep the volume of distribution at steady state (Vss) was 98.66 +/- 4.67 mL/kg. Distribution into tissue cages was slow; the drug was detectable in tissue cages at two hours after administration, peaks were detected of 22.32 +/- g/mL (mean +/- SE) in exudate at 9.50 +/- 0.73 h and 22.07 +/- 1.57 g/mL in transudate at 11.5 +/- 1.92 h. Up to 20 h after administration, concentrations were lower in exudate or transudate than in plasma; after this time they were lower in plasma than in the tissue cage fluids. The area under the curve (AUC) ratio of exudate to plasma was higher than that of transudate to plasma. (J289.21.w2)
Plasma Protein binding / Storage
  • In cattle:
    • 93% plasma protein bound (highly bound) at serum levels of 100 g/mL. [1979] (J289.2.w1)
    • Following repeated oral dosing of cows with 2.5 g (approximately 5 mg/kg bodyweight) twice daily for eight days, it was noted that the fraction of the drug that was unbound increased non-linearly with increasing plasma drug concentration, from 0.22% at 10 g/mL plasma to 2.2 % at 153 g/mL plasma. (J289.7.w1)
  • In goats: 
    • 60.3% plasma protein bound (S.D. 4.79). (J13.33.w1)
    • Plasma protein binding was 98-99% in kids from 10-days-old to adult; in kids of one-day-old binding was 95.4% +/- 2.2% (mean +/- SEM). (J289.16.w2)
  • In sheep:
    • Data from a tissue cage model of phenylbutazone pharmacokinetics in sheep indicated that plasma protein binding may be less in sheep than in equines or cattle, since there was higher extravascular penetration into both exudate and transudate, suggesting more unbound drug available for penetration into both inflamed and non-inflamed tissue cage fluids. (J289.21.w2)
Elimination Route
  • In cattle:
    • In milk: Following repeated oral dosing of cows with 2.5 g (approximately 5 mg/kg bodyweight) twice daily for eight days, while minimum plasma concentration during steady state was 100.4 +/1 7.3 g/mL plasma (mean +/- SD) the concentration in milk never exceeded 1% of the concentration in plasma. Five days after administration of phenylbutazone had been discontinued the concentration of the drug in the milk was 0.05 +/- 0.01 g/mL. Mammary clearance of the drug increased at higher plasma concentrations; this was presumed to be due to the fact that less of the drug is plasma protein bound at higher concentrations. (J289.7.w1)
Elimination half-life / Clearance Rate
  • Varies considerably between species and also in animals of different ages within a species. (J13.54.w1)
  • Half-life in dogs 1-6 hours and rapid elimination of the active metabolite oxyphenbutazone. (B322.3.w3)

Cattle:

  • Elimination half-life 36-55 hours. (B340.10.w10)
  • Elimination half time 32.4-60.8 hours (mean 42.4 hrs) following intravenous administration of 6 mg/kg in healthy dairy cows; this was not significantly affected by a dose rate of 6 mg/kg or 3 mg/kg. [1979] (J289.2.w1)
  • Total body clearance mean 0.0016 l/kg/h. [1979](J289.2.w1)
  • Biological half-lives in cows of 31.4-82.1 hours following intravenous administration and 38.6-78.2 hours following oral administration. [1980] (J289.3.w1)
  • Total body clearance varied 0.78-1.94 mL/kg/h. [1980] (J289.3.w1)
  • Following repeated oral dosing of cows with 2.5 g (approximately 5 mg/kg bodyweight) twice daily for eight days, elimination half-life in plasma was 38.6 +/- 3.7 h (mean +/- SD). (J289.7.w1)
  • Mean elimination half-life following intravenous inoculation at 4.4 mg/kg of 35.9 hours for six adult cows; mean clearance of 2.77 mL per kg per hour. Longer half-lives were obtained following either intramuscular or oral dosing. (J21.44.w1)
  • Mean total body clearance in mature Holstein bulls 0.0015 +/- 0.0003 L/kg/hr. Harmonic mean biological half life 61.6 +/- 7.2 hours following intravenous administration at 10 mg/kg and 62.6 +/- 12.9 hours following oral administration. (J13.51.w2)
  • Mean clearance 0.0021 +/- 0.0001 L/kg/h for steady-state after multiple oral dosing of mature Holstein bulls. Elimination half-life 61.8 +/- 12.8 hours (SEM). (J13.51.w3)
  • Elimination half-life of 207 hours for healthy calves, 168 hours for endotoxaemic calves; clearance 0.708 mL/kg/h (0.828 mL/kg/hr for endotoxaemic calves) for a single dose of 5 mg/kg bodyweight intravenously. (J13.54.w1)
  • In calves age 4-5 months and weighing 77-105 kg data from administration of 4.4 mg/kg, either intravenously or orally, showed slow clearance (1.29 mL/kg/h) and long terminal half-life (53.4 h for intravenous administration, 57.9 h for oral administration). (J289.25.w1)
  • Mean clearance 3.2 mL/kg/h and terminal elimination half-life 34 +/- 9 h following intravenous administration of 6 mg/kg in beef steers 234-354 kg. Mean t1/2 of free drug was 35 +/- 12 h. (J289.25.w2)
  • Phenylbutazone pharmacokinetics in the cow are non-linear; this is attributable to the concentration-dependent plasma protein binding of phenylbutazone. Following a single intravenous dose of 6 mg/kg in cattle, clearance and volume of distribution are both lower for total phenylbutazone than for unbound drug due to the high degree of binding to plasma proteins; half life is longer for total phenylbutazone. (J289.13.w1)
  • In cows following administration of 7.5 mg/kg intravenously once residues in muscle and liver declined to below 0.1 g/g after about 14 days. (J4.211.w1)
Goats: 
  • T1/2 14.5 hours. T1/2 was longer for males than for females but this was not significant. (J13.33.w1) Kd (first order disappearance rate kinetic constant) 0.047 hour-1. (J13.33.w1)
  • In goats following intravenous administration to mixed-breed adult goats at 4.4 mg/kg elimination half-life t1/2β of 15.3 +/- 1.15 hrs (mean +/- SE) and following oral administration at the same dose rate the elimination half-life was 22.0 +/- 3.32 hours. Clearance Clβ following intravenous administration was 4.46 +/- 1.12 mL/kg/h. Note: phenylbutazone was still detectable in plasma 144 hours after administration. (J3.140.w7)
  • In goats following administration of phenylbutazone intravenously (10 mg/kg), elimination half-life t1/2β was 119.1 +/-6.5 h in one-day-old kids, 64.3 +/- 7.6 h in 10-day-old kids, 44.9 +/- 11.2 h in four-week-old kids, 28.9 h in six-week-old kids and 15.9 +/- 1.5 h in adults; values for kids of all ages were significantly different (P<0.05) from the value for adults. Clearance Cl(B) was 2 +/-0 mL/h/kg in one-day-old kids, 4 +/-1 mL/h/kg in 10-day-old kids, 4 +/- 1 mL/h/kg in four-week-old kids, 6 +/- 1 mL/h/kg in six-week-old kids and 13 +/- 1 mL/h/kg adults; values for kids of all ages were significantly different (P<0.05) from the value for adults. From 10 days to four weeks of age the clearance did not change but the elimination half life decreased; this would be due to the decreased volume of distribution. From six weeks to adult the volume of distribution did not change significantly but the elimination half-life decreased, which was probably due to increased body clearance, most likely reflecting maturation of metabolism. (J289.16.w2)

Sheep:

  • Following administration of phenylbutazone at 4.4 mg/kg intravenously in male one-year-old sheep elimination was slow; the drug was still detectable in plasma in six of eight animals at 144 h after administration, at a concentration of 0.32 +/- 0.1 g/mL. The elimination half-life t1/2β in plasma was 17.92 +/- 1.74 h (mean +/- SE) with a mean retention time of 22.22 +/- 1.73 h and clearance ClB of 4.56 +/- 0.53 mL/kg/h. Elimination from tissue-cage fluids was slower than from plasma (P<0.05): in exudate the mean retention time was 31.60 +/- 1.84 h and in transudate the mean retention time was 31.11 +/- 2.41 h. (J289.21.w2)
Drug Interactions --

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Administration
Formulations available
  • In the UK this NSAID is presently available for use in the dog and the horse in various formulations including tablets, oral paste, oral powder and a sterile aqueous solution for injection. (B322.3.w3, B266)
  • In the USA this drug is presently available in a variety of formulations for use in horses and dogs, including tablets, oral paste and injectable forms. (B263)
Doses / Administration Routes / Frequencies Cattle:
  • Note: "The therapeutic range of plasma concentrations for PBZ [phenylbutazone] in cattle has not been established."[2002](J289.25.w1)
  • 4 mg/kg intravenously or orally every 24 hours. (B263, B362.w1)
  • 4-8 mg/kg orally or 2 - 5 mg/kg intravenously. (B263)
  • 10-20 mg/kg orally then 2.5 - 5.0 mg/kg orally every 24 hours or 10 mg/kg orally every 48 hours. (B207.2.w2, B263)
  • Suggested loading dose of 9 mg/kg followed by 4.5 mg/kg every 48 hours, based on experimental pharmacokinetic data and therapeutic levels suggested for horses. [1979](J289.2.w1)
    • Note: recent [2002] data suggest that a plasma concentration of 20 g/mL would not be effective in cattle. (J289.25.w1)
  • Suggested oral loading dose of 10 - 20 mg/kg with a daily maintenance dose of 2.5-5 mg/kg, based on disposition kinetics recorded and on the therapeutic concentration range suggested for humans (to give a range of 60-90 g/mL). [1980] (J289.3.w1)
  • 10 - 20 mg/kg orally loading dose followed by 2.5-5 mg/kg every 24 h or 10 mg/kg every 48 h. (J4.191.w12)
  • 5 mk/kg orally, initially daily then every other day for analgesia in degenerative joint disease or septic arthritis (B344.32.w32)
  • 6 g per (adult) animal, intravenously or intramuscularly, or 4 - 6 g per (adult) animal, intravenously or intramuscularly, followed by up to 2 g per (adult) animal daily. (J4.211.w1)
  • Suggested dose of 4-6 mg/kg every 24 hours or 10 - 14 mg/kg every 48 hours to provide therapeutic plasma concentrations with a minimum steady-state concentration of 50-70 g/mL. (J13.51.w3)
    • It was noted that "doses of 6g of PBZ/1,000 kg of body weight given daily appear effective in controlling pain that would otherwise preclude the collection of quality semen from crippled bulls." (J13.51.w3)
Experimental data:
  • A study in calves age 4-5 months and weighing 77-105 kg data from administration of 4.4 mg/kg, either intravenously or orally, indicated that higher doses would probably be required for clinical efficacy from a single dose, since this dose rate did not produce a statistically significant inhibition of exudate prostaglandin E2 (PGE2), leukotriene B4 (LTB4), β-glucuronidase concentrations, exudate leucocyte numbers, serum thromboxane B2 (TxB2) or bradykinin-induced skin swelling. ExudatePGE2 was decreased at 11 of 12 sampling times following intravenous administration but there was great variation between animals (no apparent PGE2 inhibition in two calves, about 50% inhibition in two calves and marked inhibition in one calf; much less numerical change from control values was seen following oral administration. There was a tendency (not statistically  significant) for a small (8-25%) reduction in production of a wheal in response to intradermal bradykinin following intravenous dosing with phenylbutazone. (J289.25.w1)
  • Intramuscular injection in cows at 10 mg/kg resulted in slight reactions of pain and there were some palpatory findings [pain, high skin temperature and oedema were used for assessment] which were not present following injection of physiological saline. A rise in serum creatine kinase was detected which was significantly higher than that seen following injection of saline (no rise), ketoprofen or metamizole but not significantly different from that seen with injection of flunixin meglumine. (J307.40.w1)

Sheep:

  • 1 g orally (added to the individual's concentrate ration) for three to five days. Note: this is effective but is not licensed for use in sheep in the UK. A meat withdrawal period of 28 days must be observed. (J15.17.w3)
    • This drug has been withdrawn from use for food-producing animals in the UK. [1999](J303.7.w1)
  • Possibly 10 mg/kg orally. (B322.5.w5)

Goats:

  • Experimental data: 
    • Following intravenous administration at 4.4 mg/kg platelet thromboxane B2 production was significantly inhibited (P<0.05) from one to 12 hours; after oral administration significant inhibition was seen from two to 12 hours. (J3.140.w7)

Elephants:

  • 2 mg/kg orally or intamuscularly. For degenerative joint disease. (B22.34.w13)

Elephas maximus - Asian Elephant

  • Five grams of phenylbutazone twice daily orally for one week were administered to an adult elephant, after regional digital intravenous perfusion (RDIP) of a sole abscess. (J2.34.w2)

The following information is taken with permission directly from the Elephant Care International website (W580.Aug2005.w27):

Elephants:

As of June 2003, there are no published pharmacokinetic studies however, one such study is in progress.

a) Anecdotal doses of 1-2 mg/kg every 24 hours (route of administration not specified) have been reported. This is based on a survey of 20 zoo veterinarians in the U.S. The author cautions that phenylbutazone has potential for adverse effects and that the treatment interval reported by survey participants is much shorter than that predicted by metabolic scaling (2.5 mg every 40 hours). (Mortenson, 1998, 1998, 2001).

 

b) Two cases of segmental gangrene and sloughing of elephants' ears after intravenous injection of phenylbutazone have been reported (dose not specified). The author recommends that phenylbutazone be administered orally whenever possible. (Miller, 1977).

Elephant References:

a )Mortenson,J. and Sierra S. 1998. Determining dosages for antibiotic and anti-inflammatory agents in elephants. Proceedings of the First North American Conference on Elephant Foot care and Pathology. Pages: 50-55 Abstract: Clinical application of drug use in elephants for safe, reliable, and effective results necessitates the establishment of a treatment response curve or blood concentration profile for each drug and species (African vs. Asian).  Because of the difficulty in obtaining accurate pharmacokinetic information, it is more common to select a drug dosage and frequency interval used in other species, specifically the cow and the horse.  Where treatment monitoring with serum concentrations of the drug are difficult to obtain, extrapolation of treatment regimens between species of extraordinary size difference may be done by metabolic scaling to establish drug dosage rates and frequency intervals.  The principle of metabolic scaling of pharmacokinetic parameters is based on the well established scaling of physiological processes across animals of various sizes. The goals of this paper are to cover what antibiotics are currently used now with Asian and African elephants by surveying North American zoos, reviewing standard equine doses, discussing metabolic scaling attempts, and reviewing pharmacokinetic studies done. Based on the survey, zoo veterinarians generally are not utilizing metabolic scaling formulas to determine antibiotic and anti-inflammatory drug dosages for elephants. It appears that several drugs are being dosed too frequently (amikacin, amoxicillin), and not frequent enough (trimethoprim-sulfamethoxazole) based on pharmacokinetic study results. Metabolic scaling dosages and treatment intervals do not correspond well with antibiotic pharmacokinetic studies done in both African and Asian elephants.

a) Mortenson,J. 1998. Determining dosages for anti-inflammatory agents in elephants. Proceedings AAZV and AAWV Joint Conference. Pages: 477-479

  a) Mortenson,J., 2001. Determining dosages for antibiotics and anti-inflammatory agents. In: Csuti,B., Sargent,E.L., and Bechert,U.S. (Editors), The Elephant's Foot. Iowa State University Press, Ames, Iowa, USA pp. 141-144

  b) Miller,R.M. 1977. Segmental gangrene and sloughing of elephants' ears after intravenous injection of phenylbutazone. Veterinary Medicine Small Animal Clinician 72 (4): 633-637

 

Monitoring parameters --

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Withdrawal period / Withholding time
Notes This drug has a long elimination half-life and the potential for residues in animals following treatment is high. (J4.211.w1)

UK:

  • This drug has been withdrawn from use for food-producing animals in the UK. [1999](J303.7.w1)
  • "Phenylbutazone is an inexpensive and effective analgesic in sheep, but, as well as being unlicenced for use in sheep in the UK, a 28-day meat withholding period must be observed." [1995](J15.17.w3)
USA:
  • Not approved for use in animals intended for food. [2002](B263)
    • Following administration at 6 g per (adult) animal, intravenously or intramuscularly, withdrawal times of 96 hours for milk and 12 days for meat recommended; following administration at 4-6 g per (adult) animal, intravenously or intramuscularly, followed by up to 2 g per (adult) animal daily, withdrawal times of 120 hours for milk and 21 days for meat recommended. [1997](J4.211.w1)
    • "While phenylbutazone is not approved for use in cattle, it is used. A general guideline for meat withdrawal times are: one dose=30 days, 2 doses=35 days, and 3 doses=40 days. Contact FARAD for more information."  (B263)
    • Use in food animals is strongly discouraged in the USA by FARAD and the FDA-Center for Veterinary Medicine, with a tolerance level for the drug in any animal product of zero; the withdrawal period is long and any concentration of the drug detected in animal products in the USA is illegal. (J234.19.w1)
    • N.B. Effective 29th May 2003, phenylbutazone was added to the list of drugs prohibited for use in female dairy cattle aged 20 months or older in the USA. (W509.June04.w1)

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Toxic Information

Toxic effects of Pharmaceutical Products
Contraindications / Precautions NOTE: Not approved for use in food-producing animals in many countries due to the risks of residues entering the food chain and the known toxicity to humans. (B207.2.w2)
Adverse Effects / Side Effects / Warnings
  • Hepatotoxicity has been reported associated with use in elderly horses. (B322.3.w3)
  • Following repeated oral dosing of cows with 2.5 g (approximately 5 mg/kg bodyweight) twice daily for eight days, all cows remained clinically healthy, however white blood cell concentration had decreased to about two thirds of control values (P<0.001); there were also significant decreases in the relative lymphocyte count (P<0.05) and in total bilirubin concentration (P<0.001). Biochemical changes noted were a significant (P<0.001) decrease in plasma sodium and increase (P<0.05) in plasma albumin. (J289.7.w1)
Operator Warnings --
Overdose / Acute Toxicity --

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Detailed Toxicological Information
Classification --
Acute Toxicity --
Chronic Toxicity
  • No gross or histological lesions consistent with NSAID toxicosis were observed following administration to neonatal calves of 10 mg/kg loading dose followed by nine days at 5 mg/kg. (J13.54.w1)
  • "Prolonged low dose therapy with phenylbutazone in cattle with painful arthritides has not led to any demonstrable deleterious effects such as gastrointestinal ulceration or renal papillary necrosis." (B344.32.w32)
Reproductive effects --
Teratogenic effects --
Mutagenic effects --
Carcinogenic effects

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Organ toxicity --
Bird Toxicity
  • Hepatotoxicity has been reported associated with use in elderly horses. (B322.3.w3)
Aquatic organism activity --
Other organism toxicity --

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Nutrient Information

Nutritional Data
Sources --
Biological Use --
Recommended Daily Allowance / Recommended level in food --
Stability in food (Storage time) --
Interactions --

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External / Environmental Information

External / Environmental Uses
Use --
Formulation --
Application method --
Application Concentration --
Persistence of Effect / Frequency of Application --

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Sources in the Environment
Natural sources --
Human-associated sources --

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Effects on the Environment
Effects in the aquatic environment

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Effects on land --

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Persistence in the Environment
Breakdown in soil and groundwater

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Breakdown in water --
Breakdown in vegetation --

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