KETOPROFEN
Chemistry - A propionic acid derivative nonsteroidal anti-inflammatory agent, ketoprofen occursas an off white to white, fine to granular powder. It is practically insoluble in water, but freelysoluble in alcohol at 20°C. Ketoprofen has a pKa of 5.9 in a 3:1 methanol:water solution.
Uses, Indications - Ketoprofen is labeled for use in horses for the alleviation of inflammation andpain associated with musculoskeletal disorders. Like flunixin (and other NSAIDs), ketoprofenpotentially has many other uses in a variety of species and conditions; however well controlledstudies for these uses are generally unavailable.
Oral absorption characteristics in horses was not located. It has been reported that when comparing IV vs. IM injections in horses, the areas under the curve are relatively equivalent.
While distribution characteristics are not well described, the drug does enter synovial fluid and ishighly bound to plasma proteins (99% in humans, and approximately 93% in horses). In horses, the manufacturer reports that the onset of activity is within 2 hours and peak effects 12 hours postdose.
Ketoprofen is eliminated via the kidneys both as a conjugated metabolite and unchanged drug. Theelimination half life in horses is approximately 1.5 hours.
The manufacturer cautions against ketoprofen's use in breeding animals, because effects onfertility, pregnancy or fetal health have not been established in horses. However, rat and micestudies have not demonstrated increased teratogenicity or embryotoxicity. Rabbits receiving twicethe human dose exhibited increased embryotoxicity, but not teratogenicity. Because non-steroidalantiinflammatory agents inhibit prostaglandin synthesis, adversely affecting neonatal cardiovascularsystems (premature closure of patent ductus), ketoprofen should not be used late in pregnancy.
Studies in male rats demonstrated no changes in fertility.
It is presently unknown whether ketoprofen enters equine milk. Ketoprofen does enter caninemilk.
Do not administer intra-arterially and avoid SubQ injections. While not labeled for IM use inhorses, it reportedly is effective and may only cause occasional inflammation at the injection site.
Humans have survived oral ingestions of up to 5 grams. The LD50 in dogs after oral ingestion hasbeen reported to be 2000 mg/kg. General drug removal and supportive measures have beenrecommended in cases of oral overdosage.
Because ketoprofen may inhibit platelet aggregation and also cause gastrointestinal ulceration, when used with other drugs that alter hemostasis (e.g., heparin, warfarin, etc.) and/or cause gastrointestinal erosion (e.g., aspirin, flunixin, phenylbutazone, corticosteroids, etc.), increased likelihood of bleeding or ulceration may occur.
Ketoprofen and probenecid are not recommended to be used together. Probenecid reduces renal clearance of ketoprofen and also reduces its protein binding; thereby increasing the risk of toxicity.
NSAIDs (including ketoprofen) may potentially significantly reduce the excretion ofmethotrexate and cause toxicity.
Laboratory Considerations - Ketoprofen may cause falsely elevated blood glucose values when using the glucose oxidase and peroxidase method using ABTS as a chromogen; falsely elevated serum bilirubin values when using DMSO as a reagent; falsely elevated serum iron concentrations using the Ramsey method, or falsely decreased serum iron concentrations when using bathophenanthroline disulfonate as a reagent.
Storage, Stability, Compatibility
Ketoprofen oral capsules should be stored at room temperature in tight, light resistant containers. The veterinary injection should be stored at room temperature. Compatibility studies with injectable ketoprofen and other compounds have apparently notbeen published.Pharmacology - KETOPROFEN
Ketoprofen exhibits actions similar to that of other nonsteroidal antiinflammatoryagents in that it possesses antipyretic, analgesic and antiinflammatory activity. Its purportedmechanism of action is the inhibition of cyclooxygenase catalysis of arachidonic acid toprostaglandin precursors (endoperoxides), thereby inhibiting the synthesis of prostaglandins intissues. Ketoprofen purportedly has inhibitory activity on lipoxygenase, whereas flunixin reportedlydoes not at therapeutic doses.Uses, Indications - Ketoprofen is labeled for use in horses for the alleviation of inflammation andpain associated with musculoskeletal disorders. Like flunixin (and other NSAIDs), ketoprofenpotentially has many other uses in a variety of species and conditions; however well controlledstudies for these uses are generally unavailable.
Pharmacokinetics - KETOPROFEN
In species studied (rats, dog, man), ketoprofen is rapidly and nearly completely absorbed after oral administration. The presence of food or milk decreases oral absorption.Oral absorption characteristics in horses was not located. It has been reported that when comparing IV vs. IM injections in horses, the areas under the curve are relatively equivalent.
While distribution characteristics are not well described, the drug does enter synovial fluid and ishighly bound to plasma proteins (99% in humans, and approximately 93% in horses). In horses, the manufacturer reports that the onset of activity is within 2 hours and peak effects 12 hours postdose.
Ketoprofen is eliminated via the kidneys both as a conjugated metabolite and unchanged drug. Theelimination half life in horses is approximately 1.5 hours.
Contraindications, Precautions, Reproductive Safety
While the manufacturer states that thereare no contraindications to the drug's use (other than previous hypersensitivity to ketoprofen), itshould be used only when the potential benefits outweigh the risks in cases where GI ulceration orbleeding is evident or in patients with significant renal or hepatic impairment. Ketoprofen may maskthe signs and symptoms (inflammation, hyperpyrexia) of infection. Because ketoprofen is highlyprotein bound, patients with hypoproteinemia may have increased levels of free drug, therebyincreasing the risks for toxicity.The manufacturer cautions against ketoprofen's use in breeding animals, because effects onfertility, pregnancy or fetal health have not been established in horses. However, rat and micestudies have not demonstrated increased teratogenicity or embryotoxicity. Rabbits receiving twicethe human dose exhibited increased embryotoxicity, but not teratogenicity. Because non-steroidalantiinflammatory agents inhibit prostaglandin synthesis, adversely affecting neonatal cardiovascularsystems (premature closure of patent ductus), ketoprofen should not be used late in pregnancy.
Studies in male rats demonstrated no changes in fertility.
It is presently unknown whether ketoprofen enters equine milk. Ketoprofen does enter caninemilk.
Adverse Effects, Warnings
Because ketoprofen is a relatively new agent, its adverse effectprofile in horses has not been clearly elucidated. Preliminary studies and reports indicate thatketoprofen appears relatively safe to use in horses and may have a lower incidence of adverse effects than either phenylbutazone or flunixin. Potentially, gastric mucosal damage and GI ulceration, renal crest necrosis, and mild hepatitis may occur.Do not administer intra-arterially and avoid SubQ injections. While not labeled for IM use inhorses, it reportedly is effective and may only cause occasional inflammation at the injection site.
Overdosage, Acute Toxicity
Horses given ketoprofen at doses up to 11 mg/kg administered IVonce daily for 15 days exhibited no signs of toxicity. Severe laminitis was observed in a horse given33 mg/kg/day (15X over labeled dosage) for 5 days. Anorexia, depression, icterus, and abdominalswelling was noted in horses given 55 mg/kg/day (25X labeled dose) for 5 days. Upon necropsy, gastritis, nephritis and hepatitis were diagnosed in this group.Humans have survived oral ingestions of up to 5 grams. The LD50 in dogs after oral ingestion hasbeen reported to be 2000 mg/kg. General drug removal and supportive measures have beenrecommended in cases of oral overdosage.
Drug Interactions
Because ketoprofen is highly bound to plasma proteins, it can displace or bedisplaced by other highly protein bound drugs, including warfarin, phenylbutazone, etc.Because ketoprofen may inhibit platelet aggregation and also cause gastrointestinal ulceration, when used with other drugs that alter hemostasis (e.g., heparin, warfarin, etc.) and/or cause gastrointestinal erosion (e.g., aspirin, flunixin, phenylbutazone, corticosteroids, etc.), increased likelihood of bleeding or ulceration may occur.
Ketoprofen and probenecid are not recommended to be used together. Probenecid reduces renal clearance of ketoprofen and also reduces its protein binding; thereby increasing the risk of toxicity.
NSAIDs (including ketoprofen) may potentially significantly reduce the excretion ofmethotrexate and cause toxicity.
Laboratory Considerations - Ketoprofen may cause falsely elevated blood glucose values when using the glucose oxidase and peroxidase method using ABTS as a chromogen; falsely elevated serum bilirubin values when using DMSO as a reagent; falsely elevated serum iron concentrations using the Ramsey method, or falsely decreased serum iron concentrations when using bathophenanthroline disulfonate as a reagent.