Chemicals / Complex Chemical Agents/ Chemical:

Ketoprofen (with special reference to Elephants, Ruminants, Hedgehogs, Bears, Lagomorphs, Ferrets and Great Apes)

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 

Non-steroidal anti-inflammatory drug with anti-inflammatory, analgesic and antipyretic activity (B201.10.w10, B263, J289.27S1.w1)

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Names and Formulae

Type Phenylpropionic acid derivative NSAID. (B135, B263, B266); in the 2-arylpropionic acid class. (J13.62.w1)
Alternative Names "2-(meta-Benzoylphenyl) propionic acid; Orudis; Oruvail; Alrheumat." (W324); Ketofen (Merial Animal Health Ltd) (B266), "benzeneacetic acid, 3-benzoyl-alpha-methyl-, (+)-" (J289.27S1.w1)
Chemical Formula C16H14O3 (W324, J289.27S1.w1)
Chemical Structure

Contains a single asymmetic carbon atom, therefore has two enantiomers, R (-) ketoprofen and S(+) ketoprofen. (J13.62.w1, J289.20.w2)

Available forms are a racemic (50:50) mixture of the R (-) enantiomer and the S (+) enantiomer. (B263, B201.10.w10)

The S(+) enantiomer is responsible for blockage of cyclooxygenase enzymes and is considered to be responsible for the analgesic and anti-inflammatory properties of ketoprofen. (J13.62.w1)

Molecular Weight 254.2848. (W324)
Related Chemicals --

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Physical Properties / Chemistry

Appearance
  • White to off-white fine to granular powder, odourless and nonhygroscopic. (B263, J289.27S1.w1)

Melting point
  • About 95C. (J289.27S1.w1)
Boiling point --
Density --
Water solubility
  • Practically insoluble. (B263)
  • 0.3 g/mL at pH 7.0. (W324)
Other solubility
  • Freely soluble in alcohol (ethanol) at 20C. (B263, J289.27S1.w1)
  • Freely soluble in chloroform, acetone and ether. (J289.27S1.w1)
  • Soluble in strong alkali. (J289.27S1.w1)
Acid/Base
  • Weak acid. (B135)
  • pKa 5.9 (in a 3:1 methanol:water solution). (B263)
  • pKa 5.02 (J289.27S1.w1)

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Pharmacology & General Information

Pharmacology
  • Reversible inhibition of the enzyme cyclooxygenase (prostaglandin synthetase) thereby decreasing the formation of prostaglandins and thromboxane A2. (B135, J289.27S1.w1)
    • Considered to be one of the more potent inhibitors of prostaglandin synthesis. (J289.27S1.w1)
    • Relatively nonselective: inhibits COX-1 slightly more than COX-2 in some species, but this is reversed in other species. (J289.27S1.w1)
  • Reduces inflammation by decreasing the release of mediators from granulocytes, basophils and mast cells, decreasing sensitivity of vessels to bradykinin and histamine, affecting lymphokine production from T -lymphocytes and reversing vasodilatation. (B135)
  • Also some ability to inhibit lipoxygenase enzyme. (B135)
    • In vivo tests have not confirmed the in vitro finding of lipoxygenase inhibition. (J289.27S1.w1)
  • S (+) enantiomer has greater anti-inflammatory potency than the R (-) enantiomer. (B263)
  • Chiral inversion from R(-) to S(+) occurs to various extents depending on the species: e.g. 49% in horses and 41% in calves. (J289.20.w2)
  • Chiral inversion from R(-) to S(+) occurs in sheep. (J13.62.w1)
  • Antithrombotic: inhibits production of thromboxane B2 (platelet aggregation promoter). (J289.27S1.w1)
  • Antipyrexic: "believed to occur by inhibition of prostaglandins in the hypothalamus." (J289.27S1.w1)
Storage / Stability Store below 25C and protect from light. Use within 28 days after withdrawing the first dose from the bottle. Keep out of reach of children. (B266 - Data sheet information for Ketofen 10%, Merial Animal Health Ltd.)
  • Protect from direct sunlight. (J289.27S1.w1)
  • Store between 15 and 30 C (59-86 F) unless otherwise specified by the manufacturer. (J289.27S1.w1)
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

--
Authors Debra Bourne (V.w5)
Referees Suzanne I. Boardman (V.w6); A.B.Forbes BVM&S.,CBiol.,MIBiol.,DipEVPC.,MRCVS (V.w66)

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Therapeutic Information

Uses/Indications

Activity
  • NSAID general: analgesic, antipyretic, with both peripheral and central anti-inflammatory activity; also inhibits platelet aggregation. (B135)
    • Antithrombotic: inhibits production of thromboxane B2 (platelet aggregation promotor). (J289.27S1.w1)
    • Antipyrexic: "believed to occur by inhibition of prostaglandins in the hypothalamus." (J289.27S1.w1)
    • Analgesic: by interruption of the mediators of inflammation such as bradykinin, and possibly by central mechanisms. (J289.27S1.w1)
    • Analgesic, anti-inflammatory, antipyretic, antiendotoxic. (J13.62.w1)

Specific studies:

  • Following administration of ketoprofen (racemic mixture) at 3 mg/kg in calves (20 weeks old, 118.9 +/- 4.2 kg bodyweight) ketoprofen significantly inhibited serum thromboxane (TxB2), exudate prostaglandin (PGE2), β-glucuronidase (β-glu) and bradykinin-induced oedematous tissue swelling, with the mean EC50 being 0.118 g/mL, 0.08 g/mL, 0.06 g/mL and 0.00029 g/mL respectively. There was no significant inhibition of leukotriene (LTB4)(J289.18.w1)
  • Ketoprofen at 6 mg/kg intravenously in calves at one hour before and three hours after administration of Escherichia coli heat-stable endotoxin to induce diarrhoea, reduced fecal output measured at eight and 24 hours. No effect of fecal output was seen with a dose of 3 mg/kg. (J13.54.w4)
Appropriate Use

In cattle:

UK:

  • "The supportive treatment of parturient paresis associated with calving;
  • Reducing the pyrexia and distress associated with bacterial respiratory disease when used in conjunction with antimicrobial therapy as appropriate;
  • Improving the recovery rate in acute clinical mastitis, including acute endotoxic mastitis, caused by gram negative microorganisms, in conjunction with antimicrobial therapy;
  • Reducing oedema of the udder associated with calving"

(B266 - UK data sheet information for use of Ketofen 10% in the UK, Merial Animal Health Ltd.)

Canada:

  • Alleviation of inflammation and pain associated with musculoskeletal disorders. (J289.27S1.w1)
  • Symptomatic treatment of fever. (J289.27S1.w1)
  • Alleviation of inflammation and pain associated with a variety of nonmusculoskeletal conditions. (J289.27S1.w1)
  • Alleviation of fever, pain and inflammation associated with acute clinical mastitis. Note: should be given in conjunction with primary therapy including antimicrobials, and supportive treatment. (J289.27S1.w1)
Limitations
  • Not labelled for use in food-producing animals in the USA. (J289.27S1.w1)
  • Not labelled for use in small ruminants (sheep, goats) in the UK or Canada or USA. (J289.27S1.w1)
Notes --

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Pharmacokinetics and Drug Interactions

Absorption /Bioavailability
  • Rapid absorption. (B135)
  • In humans, dogs and rats absorption following oral administration is rapid and nearly complete, but is decreased by the presence of food or milk. (B263)
  • Onset of activity in horses within two hours of administration and peak activity at 12 hours. (B263)
Distribution
  • Ketoprofen is known to enter synovial fluid. (B263)

In cattle:

  • Following administration of ketoprofen (racemic mixture) at 3 mg/kg in calves (20 weeks old, 118.9 +/- 4.2 kg bodyweight) distribution was rapid, with a distribution half-life of 0.03 h and the volume of distribution was low, being 0.20 +/- 0.06 L/kg for R(-) and 0.22 +/- 0.06 L/kg for S(+) ketoprofen. (J289.18.w1)
  • Following administration of ketoprofen intravenously at 3.31 mg/kg in lactating Holstein dairy cows, mean retention peaked at 3.6 minutes with a distribution half-life of 4.25 minutes. The calculated steady state volume of distribution was 0.106 L/kg (harmonic mean, range 0.0947-0.125 L/kg). (J13.57.w3)

In sheep:

  • In sheep following intravenous injection of 3 mg/kg of the racemate, distribution was rapid; distribution half-life was  0.127 +/- 0.032 for R(-) and 0.138 +/- 0.013 h for S(+). volume of distribution (Vdss) was 0.168 +/- 0.015 L/kg for R(-) and 0.256 +/- 0.021 L/kg for S(+). Rapid penetration into exudate; concentrations in exudate were relatively low but persistence in exudate was prolonged. (J289.22.w1)
  • In Dorset cross sheep following administration of 3 mg/kg racemic ketoprofen intravenously, distribution half-life t1/2α was 0.11 +/- 0.02 h (mean +/- SEM) for S(+) and 0.10 +/- 0.02h for R(-) ketoprofen. The volume of distribution at steady state (Vss) was low: 0.18 +/- 0.02 L/kg for S(+) and 0.11 +/- 0.01 L/kg for R(-). Following intravenous administration of 1.5 mg/kg of S(+) ketoprofen, t1/2α was 0.13 +/- 0.02 h and Vss was 0.23 +/- 0.02 L/kg. Following intravenous administration of 1.5 mg/kg of R(-) ketoprofen, t1/2α was 0.17 +/- 0.03 h and Vss was 0.18 +/- 0.04 L/kg. Following administration of the racemate, exudate concentration of S(+) was 0.19 g/mL at one hour increasing to 0.29 g/mL at six hours and was still present in measurable concentrations at 12 hours and the mean exudate AUC was about two thirds that for plasma; the mean R(-) ketoprofen concentration rose from -.24 g/mL at one hour to 0.50 g/mL at six hours and was still found in measurable concentrations at 24 hours; the AUC was about two thirds that for plasma. R(-) predominated in plasma; mean penetration half life was 2.23 h for S(+) and 1.59 h for R(-) ketoprofen. When S(+) was administered the mean concentration in exudate was constant between one and six hours with concentrations then decreasing to undetectable levels by nine hours; the mean AUC and the maximum concentration were similar to those seen following racemate administration. When R(-) was administered the concentration of R(-) in exudate increase, from 0.34 g/mL at one hour to 0.52 g/mL at nine hours after administration with a maximum concentration of 0.59 g/mL. The area under the curve was higher for R(-) than for S(+) (6 gh/mL versus 3.12 gh/mL)  indicating predeominence of R(-) in the exudate. S(+) was not detected in exudate after administration of R(-). (J13.62.w1)

In goats:

  • In goats (lactating Togenberg does, 1-4 years old, 49-59 kg) following intravenous administration of 2.2mg/kg ketoprofen, the volume of distribution at steady state was 0.23 +/- 0.051 L/kg. (J289.21.w1)
  • In goats following intravenous administration of 3 mg/kg of the racemate t1/2 for distribution was 0.19 +/- 0.01 (mean and SEM) hrs for R(-) and 0.18 +/- 0.01 h (mean and SEM) for S(+). Volume of distribution (Vdss) was 0.29 +/- 0.05 L/kg for R(-) and 0.39 +/- 0.07 L/kg for S(+); differences in pharmacokinetic parameters between entantiomers were not statistically significant. Penetration of both enantiomers was greater into exudate than into transudate. R(-) showed greater penetration than S(+) into both exudate and transudate. (J289.26.w1)

Milk:

  • Minimal distribution into milk:
    • In cattle: Following administration of ketoprofen intravenously at 3.31 mg/kg in lactating Holstein dairy cows, although ketoprofen was detectable (detection limit >27 ng/mL) in samples taken at 10-120 minutes post injection, it was always less than the quantification limit of 90 ng/mL. (J13.57.w3)
    • In goats: In goats (lactating Togenberg does, 1-4 years old, 49-59 kg) following intravenous administration of 2.2mg/kg ketoprofen, levels in milk, sampled at 5-21 minutes and at 4-24 hours, were undetectable at all times (detection limit 25 ng/mL). (J289.21.w1)

Note:

  • Conversion of R(-) to S(+) occurs following injection. The extent of conversion may vary between individuals as well as between species. (J289.27S1.w1)
Plasma Protein binding / Storage
Elimination Route
  • Less than 1% excreted as unchanged drug. (B135)
  • Biotransformation is mainly hepatic. (J289.27S1.w1)
  • Eliminated via the kidneys, as a conjugated metabolite and also as unchanged drug. (B263)
  • Following parenteral administration 80% eliminated within 24 hours, mainly as conjugated metabolite. (J289.27S1.w1)
  • Minimal elimination in milk. 
    • Following administration of ketoprofen intravenously at 3.31 mg/kg in lactating Holstein dairy cows, although ketoprofen was detectable (detection limit >27 ng/mL) in some samples taken at 10 to 120 minutes post injection, it was always less than the quantification limit of 90 ng/mL. (J13.57.w3)
    • In goats (lactating Togenberg does, 1 to 4 years old, 49 to 59 kg) following intravenous administration of 2.2mg/kg ketoprofen, levels in milk, sampled at 5 to 21 minutes and at 4 to 24 hours, were undetectable at all times (detection limit 25 ng/mL). (J289.21.w1)
Elimination half-life / Clearance Rate Half-life is short. (B135)
  • Human: elimination half-life 1.8 hours. (B135)
  • Horse: elimination half-life for S(+) 1.0 hours; R (-) 0.7 hours. (B340.10.w10); approximately 1.5 hours. (B263)
  • Dog: elimination half-life of mixed drug 3.5 hours. (B340.10.w10)
  • Cat: elimination half-life of mixed drug 1.6 hours. (B340.10.w10)

In cattle:

  • Elimination half-life for S(+) 0.4 hours; R (-) 0.4 hours. (B340.10.w10)
  • Following administration of ketoprofen (racemic mixture) at 3 mg/kg in calves (20 weeks old, 118.9 +/- 4.2 kg bodyweight) the elimination half life was 0.42 hours and clearance was 0.33 L/kg/h. (J289.18.w1)
  • Following administration of ketoprofen intravenously at 3.31 mg/kg in lactating Holstein dairy cows, the elimination half-life was 29.6 minutes (0.49 h) and total clearance was 0.17 L/kg/h (range 0.14-0.19 K/kg/h). (J13.57.w3)

In sheep

  • In sheep following intravenous injection of 3 mg/kg of the racemate, clearance ClB was 0.196 +/- 0.032 L/kg/h for R(-) and 0.351 +/- 0.050 L/kg/h for S(+); elimination half-life t1/2β was 0.866 h for R(-) and 0.856 h for S(+). (J289.22.w1)
  • In Dorset cross sheep following administration of 3 mg/kg racemic ketoprofen intravenously, the elimination half- life t1/2β was 0.63 +/- 0.05 h (mean +/- SEM) for both S(+) and R(-) ketoprofen.  Clearance was rapid: ClB was 0.28 +/- 0.04 L/kg/h for S(+) and 0.16 +/- 0.02 L/kg/h for R(-). Following intravenous administration of 1.5 mg/kg of S(+) ketoprofen, t1/2β was 0.94 +/- 0.14 h and ClB was 0.32 +/- 0.02 L/kg/h. Following intravenous administration of 1.5 mg/kg of R(-) ketoprofen, t1/2β was 1.02 +/- 0.23 h and ClB was 0.16 +/- 0.01 L/kg/h. The elimination half-life from exudate was 7.44 h for S(+) and 10.32 h for R(-). (J13.62.w1)

In goats:

  • In goats (lactating Togenberg does, 1-4 years old, 49-59 kg) following intravenous administration of 2.2mg/kg ketoprofen, the elimination half-life was 0.32 +/- 0.14 h and the systemic clearance was 0.74 +/- 0.12 L/kg/h. (J289.21.w1)
  • In goats following intravenous injection of 3 mg/kg of the racemate, clearence ClB was 0.23 +/- 0.02 L/kg/h (mean +/- SEM) for R(-) and 0.30 +/- 0.03 L/kg/h for S(+); elimination half-life t1/2β was 1.87 +/- 0.28 h (mean +/- SEM) for R(-) and 1.79 +/- 0.24 h for S(+); differences in pharmacokinetic parameters between entantiomers were not statistically significant. (J289.22.w1)
Drug Interactions
  • Despite high level of binding to plasma proteins, ketoprofen does not alter the activity of warfarin or digoxin. (B135)
  • Not recommended for use concurrently with probenicid: concurrent administration of probenicid elevates the level of ketoprofen (decreases protein binding) and prolongs its plasma half-life (reduces renal clearance) therefore the risk of ketoprofen toxicity may be increased. (B135, J289.27S1.w1)
  • Do not mix injectable products with other drugs in the same syringe. (B266, J289.27S1.w1)
  • May displace or be displaced by other drugs that are highly plasma protein bound such as warfarin and phenylbutazone. (B263)
  • May inhibit platelet aggregation and also may cause gastric ulceration, therefore there is an increased likelihood of bleeding or ulceration if used with other drugs which alter haemostasis (such as heparin or warfarin) or with other drugs which cause gastrointestinal erosion, such as Aspirin, Flunixin meglumine, Phenylbutazone, corticosteroids etc. (B263)
  • May decrease the efficacy of furosamide if used concurrently. (B263)
  • As with other NSAIDs, has the potential to significantly reduce excretion of methotrexate and thus cause toxicity. (B263)
  • "Concurrent use of more than one NSAID may greatly increase the risk of gastrointestinal ulceration and renal papillary necrosis." (J289.27S1.w1)
  • "Concurrent administration of corticosteroids with NSAIDs can exacerbate injury to the gastrointestinal tract caused by these medications." (J289.27S1.w1)

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Administration

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 may also vary between different pharmaceutical formulations and depending on route of administration. In Europe the prescription cascade must be followed. In the USA FARAD may be consulted regarding residues and meat and milk withdrawal times.
Formulations available UK:
  • Tablets, ketoprofen 5mg, 20mg (Ketofen, Merial Animal Health Ltd.)
  • Injection, ketoprofen 10mg/mL (Ketofen 1%, Merial Animal Health); ketoprofen 100 mg/mL (Ketofen 10%, Merial Animal Health).

Canada:

  • Injection, ketoprofen 100 mg/mL (Rx) (Anafen) labelled for use in cattle and horses, injection 10 mg/mL (Rx) (Anafen) labelled for use in cats and dogs. (J289.27S1.w1)

USA:

  • Injection, 100 mg/mL (Rx) (Ketofen). Not labelled for use in food-producing animals. (J289.27S1.w1)
Note: Commercially available preparations contain racemic mixture of R (-) and S (+) enantiomers (i.e. mixed 50:50). (B340.10.w10, J289.27S1.w1)
Doses / Administration Routes / Frequencies

Cattle:

  • 3 mg/kg once daily, intramuscular or intravenous injection, for up to three days. (B340.10.w10, J289.27S1.w1)
    • For musculoskeletal inflammation or pain, fever, acute mastitis, general inflammation or pain. (J289.27S1.w1)
  • 3.3 mg/kg intravenously or intramuscularly every 24 hours for up to three days. (J4.211.w1)
  • In calves:
    • 2.2-6 mg/kg intramuscularly or intravenously, has been used for treatment of endotoxaemia. Note: Based on efficacy in experimentally induced disease; safety and efficacy not established for this purpose. (J289.27S1.w1)
    • 3 mg/kg intravenously suggested for treatment of postoperative pain, based on controlled studies associated with certain elective surgical procedures. (J289.27S1.w1)

Experimental data:

  • Following intravenous administration of 3 mg/kg ketoprofen, the drug inhibited the oedema produced by intradermal injection of bradykinin (AUCeff 1159.2 +/- 195.6 (SEM) percent x h), similar to tolfenamic acid given at 2 mg/kg (1167.4 +/- 178.2 percent x h) and more effective than flunixine at 2.2. mg/kg (692.3 +/- 223.2 percent x h). The drug inhibited synthesis of PGE2 in exudate (in a tissue cage) over 24 hours (AUCeff 1653 +/- 91 percent x h; values for tolfenamic acid and flunixin were similar at 1279 +/- 179 and 1651 +/- 116 percent x h respectively). Synthesis of LTB4 in exudate was not significantly inhibited by ketoprofen or the other two drugs. Ketoprofen inhibited release of β-glucuronidase for up to 24 hours (AUCeff 1197 +/- 209 percent x hour; flunixine inhibited release for 30 hours (significantly longer than tolfenamic acid or ketoprofen), AUC 2129 +/- 143 percent x hour and tolfenamic acid inhibited release for up to 12 hours with AUCeff of 671 +/- 66 percent x h. Concentrations of the exudate enzymes lactate dehydrogenase, acid phosphatase, serein protease, cysteine protease and mettaloproteases were not affected by any of the three drugs. Generation of O2- ions was affected in a dose dependent manner by all three drugs, with a significantly larger (P<0.05) inhibition for tolfenamic acid than for flunixin or ketoprofen. (J3.137.w7)
  • In calves given 6 mg/kg ketoprofen one hour before and three hours after oral administration of heat-stable Escherichia coli enterotoxin, fecal output at eight and 24 hours was less (P = 0.0588) than in calves not given ketoprofen; ketoprofen at 3 mg/kg did not reduce fecal output. (J13.54.w4)
  • Intramuscular injection in cows at 3 mg/kg produced no pain reaction although 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 higher than that seen following injection of saline (no rise) but significantly lower than that seen following injection of flunixin meglumine or phenylbutazone. (J307.40.w1)

Sheep:

  • 3 mg/kg intravenously once pre-operatively before caesarean section. (Note: not licensed for use in sheep in the UK).(J15.22.w2)
  • 3.3 mg/kg intravenously or intramuscularly every 24 hours for up to three days. (J4.211.w1)
  • 3 mg/kg intramuscularly or intravenously once daily for up to three days has been suggested based on pharmacokinetic data. Note: safety and efficacy for treatment of inflammatory conditions in sheep have not been established. (J289.27S1.w1)

Experimental data:

  • Following intravenous administration of ketoprofen to Dorset cross sheep at 3 mg/kg (racemate ketoprofen) or 1.5 mg/kg of S(+) or R(-) ketoprofen, synthesis of thromboxane (TXB2) was initially "virtually abolished" although it had returned to control values by 24 hours. Exudate prostaglandin (PGE2) concentrations were inhibited following injection of racemic ketoprofen, with maximal inhibition of 72% at six hours decreasing to 61% inhibition at 12 hours and remaining inhibited, compared to control placebo-treated sheep, at all time to 48 hours, although differences were statistically significant only to 12 hours. With the S(+) enantiomer, inhibition of PGE2 was significant at six, nine and 12 hours, but with administration of R(-) ketoprofen there was no significant inhibition of exudate PGE2. Increases in skin temperature over tissue cages following carrageenan administration were not significantly affected by any of the ketoprofen forms, nor was exudate WBC count significantly changed although following R(-) administration cell counts were consistently lower than with placebo. The EC50 (concentration producing half maximum effect) for inhibition of TXB2 in serum was 0.133 +/- 0.52 g/mL for racemate and 0.075 +/- 0.059 g/mL for S(+) ketoprofen; the EC50 for inhibition of PGE2 in exudate was 0.0065 +/- 0.0027 g/mL for racemate and 0.019 +/- 0.011 g/mL for S(+). (J13.62.w1)

Goats:

  • 3.3 mg/kg intravenously or intramuscularly every 24 hours for up to three days. (J4.211.w1)
  • 3 mg/kg intramuscularly or intravenously once daily for up to three days has been suggested based on pharmacokinetic data. Note: safety and efficacy for treatment of inflammatory conditions in goats have not been established. (J289.27S1.w1)

Cervus elaphus - Red deer:

  • Ketoprofen has been used at 2 mg/kg bodyweight for analgesia following velvet antler removal. (J290.32.w1, J290.32.w2)

Erinaceus europaeus - West European Hedgehog:

  • 2 to 4 mg/kg. Safe and effective. (V.w61)

Elephants:

The following information is taken with permission directly from the Elephant Care International website (W580.Aug2005.w18):

Elephants:
a) 1 mg/kg every 48 hours to 2 mg/kg every 24 hours in Asian elephants (Hunter et al. 2003).

Elephant references:
a) Hunter,R.P., Isaza,R., and Koch,D.E. 2003. Oral bioavailability and pharmacokinetic characteristics of ketoprofen enantiomers after oral and intravenous administration in Asian elephants (Elephas maximus). Am J Vet Res 64:(1):109-114 Abstract: OBJECTIVE: To assess oral bioavailability (F) and pharmacokinetic characteristics of the R- and S-enantiomers of ketoprofen administered IV and orally to captive Asian elephants (Elephas maximus). ANIMALS: 5 adult Asian elephants. PROCEDURE: Elephants received single treatments of racemic ketoprofen at a dose of 2.2 mg/kg, administered IV and orally, in a complete crossover design. Blood samples were collected at intervals during the 24 hours following treatment. At least 4 weeks elapsed between drug administrations. Samples were analyzed for R- and S-ketoprofen with a validated liquid chromatography-mass spectroscopic assay. Pharmacokinetic parameters were determined by use of noncompartmental analysis. RESULTS: The enantiomers of ketoprofen were absorbed well after oral administration, with median F of 101% for R-ketoprofen and 85% for S-ketoprofen. Harmonic mean half-life ranged from 3.8 to 5.5 hours, depending on route of administration and enantiomer. The area under the concentration-time curve, mean residence time, apparent volume of distribution, plasma clearance, and maximum plasma concentration values were all significantly different between the 2 enantiomers for both routes of administration. CONCLUSIONS AND CLINICAL RELEVANCE: Ketoprofen has a long terminal half-life and complete absorption in this species. Based on the pharmacokinetic data, a dosage of ketoprofen of 1 mg/kg every 48 hours to 2 mg/kg every 24 hours, PO or IV, is recommended for use in Asian elephants, although the safety and efficacy of ketoprofen during long-term administration in elephants have not been determined.

Bears:

  • Ketoprofen has been used for pain relief in a Ursus maritimus - Polar bear: a 14-month-old male polar bear being treated for a fractured lateral humeral condyl was given ketoprofen once during surgery at 2 mg/kg intramuscularly. Post-surgery, ketoprofen was given at 1 mg/kg daily for three days orally in food. (P507.2005.w6)
Lagomorphs - Oryctolagus cuniculus domesticus - Domestic rabbit:
  • 3 mg/kg intramuscularly. (B373.Guide.w41)
  • 1.0 - 3.0 mg/kg intramuscularly or subcutaneously every 24 hours. (B546)
  • 1.0 - 3.0 mg/kg orally twice daily. For analgesia. (B600.4.w4)
    • Note: Use with care in hypotensive individuals. (B600.4.w4)
  • 1.0 - 3.0 mg/kg orally every 12 hours. (B601.15.w15)
  • 1 mg/kg intramuscularly every 12 - 24 hours. (B602.41.w41)
  • 1.0 - 3.0 mg/kg orally every 12 hours. (B603.5.w5)

Ferrets - Mustela putorius furo - Ferret:

  • 1 mg/kg orally, subcutaneously or intramuscularly every 24 hours. (B602.41.w41)
  • (B626.App.w22)
  • (B631.21.w21)

Great Apes

Monitoring parameters --

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Withdrawal period / Withholding time

Notes 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 mandatory meat and milk withdrawal times for food-producing animals vary between countries and change with time. Withdrawal times may also vary between different pharmaceutical formulations and depending on route of administration. In the USA FARAD may be consulted regarding residues and meat and milk withdrawal times.

For Ketofen 10% (Merial Animal Health Ltd.) in the UK, Eire and New Zealand, 

  • Cattle: 
    • Milk nil withdrawal period, slaughter one day following intravenous injection, four days following intramuscular injection. (UK)(B201.10.w10); milk zero days, meat one day following intravenous administration, four days following intramuscular administration (B266 - Data sheet information for use in the UK of Ketofen 10%, Merial Animal Health Ltd.)
    • Milk withdrawal nil, slaughter four days. (New Zealand) (B201.10.w10)
    • Milk, established withdrawal time of zero hours, meat one day (Canada). Note: for a dose of 3 mg/kg administered every 24 hours for up to three days). (J289.27S1.w1)
  • Horses slaughter one day (following intravenous injection). (UK, Eire)(B201.10.w10)
  • Slaughter 28 days (Ketoprofen Injection (Parnell)) (New Zealand, Australia). (B201.10.w10)
  • Horses: should not be used in horses intended for human consumption. (B201.10.w10)

USA:

  • Cattle:
    • FARAD recommended withdrawal times, following use at up to 3.3 mg/kg intravenously or intramuscularly every 24 hours for up to three days: milk 24 hours, meat seven days. [1997](J4.211.w1)
  • Goats:
    • FARAD recommended withdrawal times, following use at up to 3.3 mg/kg intravenously or intramuscularly every 24 hours for up to three days: milk 24 hours, meat seven days. [1997](J4.211.w1)
  • Sheep:
    • FARAD recommended withdrawal times, following use at up to 3.3 mg/kg intravenously or intramuscularly every 24 hours for up to three days: milk 24 hours, meat seven days. [1997](J4.211.w1)

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Toxic Information

Toxic effects of Pharmaceutical Products

Contraindications / Precautions
  • Contraindicated in individuals with a history of hypersensitivity to this drug or to other propionic-class NSAIDs. (B201.10.w10, B263, B266)
  • Contraindicated following general anaesthesia until the patient has regained consciousness. (B201.10.w10)
  • Contraindicated in individuals with cardiac, renal or hepatic disease. (B201.10.w10, B266)
  • Contraindicated in individuals in which there is a possibility of gastro-intestinal ulceration or bleeding. (B201.10.w10, B266)
  • Contraindicated as a treatment concurrent with, or within 24 hours of, other NSAIDs. (B201.10.w10, B266)
  • Contraindicated in individuals with evidence of a blood dyscrasia. (B266)
  • Horses: contraindicated in racehorses prior to racing within 15 days. (B201.10.w10)
  • Horses: contraindicated in mares during pregnancy. (B201.10.w10, B266)
  • Dogs and cats: contra-indicated during pregnancy. (B266)
  • Caution in individuals with gastrointestinal ulceration or bleeding. (B263)
  • Caution in individuals with hypoproteinaemia since the levels of free drug may be increased with an increased risk of toxicity. (B263)
  • Caution in breeding animals, particularly late in pregnancy. (B263)
  • Caution in animals with significant renal or hepatic impairment. (B263)
  • Note: use may mask signs of infection such as inflammation and pyrexia. (B263)
Adverse Effects / Side Effects / Warnings
  • Can cause gastrointestinal irritation and this may lead to ulceration. (J289.27S1.w1)
  • In animals with haemodynamic compromise there may be an increased risk of ischaemia and renal damage from inhibition of prostaglandins (which produce/maintain kidney vasodilatation). (J289.27S1.w1)
  • Use with care in very young (less than six weeks old) or old animals as this may involve additional risk. Dose reduction and careful clinical management may be required. (B201.10.w10, B266)
  • Avoid using in individuals with dehydration, hypovolaemia or hypotension due to potentially increased risk of renal toxicity. (B201.10.w10, B266)
  • Avoid using concurrently with potentially nephrotoxic drugs. (B201.10.w10, B266)
  • Avoid injecting intra-arterially. (B201.10.w10)
  • Do not inject intra-arterially. (B263)
  • Avoid injecting subcutaneously. (B263)
  • Intramuscular injection in horses (off-label) is reported to be effective but may occasionally cause inflammation at the site of injection. (B263)
  • Dog and cat: rare side effects of vomiting and diarrhoea. (B266)
  • Dog and cat: following subcutaneous or intramuscular injection, slight transient swelling/local oedema may occur. (B266)
  • Potential for damage to the gastric mucosa, gastrointestinal ulceration, renal crest necrosis and mild hepatitis. However in horses the incidence of adverse effects may be lower than with Phenylbutazone or Flunixin meglumine. (B263)
Operator Warnings
  • Avoid splashes of injectable agent onto the skin or into the eyes; irrigate with copious quantity of water as required. (B266)
Overdose / Acute Toxicity
  • Main adverse effects are on the central nervous system and the gastrointestinal tract. (B135)

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Detailed Toxicological Information

Classification --
Acute Toxicity
  • Horses: up to 11.0 mg/kg intravenously for 15 consecutive days (five times recommended dose for three times the recommended duration) was tolerated without evidence of toxic effects. (B263, B266)
  • Cattle: up to 15 mg/kg per day for five consecutive days resulted in no significant adverse effects. (B266)
  • Cattle: has been administered safely to pregnant and lactating animals and to calves as young as five days old. (B266)
    • In nonruminating calves a dose of 9 mg/kg daily for six days has resulted in abomasal erosions. (J289.27S1.w1)
  • Pigs: up to 9.0 mg/kg per day (three times recommended dose) for three consecutive days resulted in no adverse effects. (B266)
Chronic Toxicity
  • Chronic administration of NSAIDs in haemodynamically compromised individuals may increase susceptibility to renal papillary necrosis. (J289.27S1.w1)
Reproductive effects
  • In rats and mice, no increased embryotoxicity reported. (B263)
  • In rabbits given twice the human dose, increased embrytoxicity was reported. (B263)
  • In male rats, no changes in fertility were reported. (B263)
  • In cattle: No effect on fetal development, gestation length, parturition or calf viability following administration of 6 mg/kg bodyweight during the sixth week of gestation or between the second month and ninth month of gestation. (J289.27S1.w1)
  • "Effect on fertility of bulls has not been evaluated." (J289.27S1.w1)
Teratogenic effects
  • In rats and mice, no increased teratogenicity reported. (B263)
  • In rabbits given twice the human dose, no increased teratogenicity was reported. (B263)
Mutagenic effects --
Carcinogenic effects

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Organ toxicity --
Bird Toxicity --
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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