Ketoprofen is one of the

propionic acid Propionic acid (, from the Greek words πρῶτος : ''prōtos'', meaning "first", and πίων : ''píōn'', meaning "fat"; also known as propanoic acid) is a naturally occurring carboxylic acid with chemical formula CH3CH2CO2H. It is a li ...

class of

nonsteroidal anti-inflammatory drug Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration o ...

s (NSAID) with

analgesic An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...

and

antipyretic An antipyretic (, from ''anti-'' 'against' and ' 'feverish') is a substance that reduces fever. Antipyretics cause the hypothalamus to override a prostaglandin-induced increase in temperature. The body then works to lower the temperature, which r ...

effects. It acts by inhibiting the body's production of

prostaglandin The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are deriv ...

. It was patented in 1967 and approved for medical use in 1980.

Medical uses

Ketoprofen is generally prescribed for arthritis-related inflammatory pains or severe toothaches that result in the inflammation of the gums. Ketoprofen topical patches are being used for treatment of musculoskeletal pain. Ketoprofen can also be used for treatment of some pain, especially nerve pain such as

sciatica Sciatica is pain going down the leg from the lower back. This pain may go down the back, outside, or front of the leg. Onset is often sudden following activities like heavy lifting, though gradual onset may also occur. The pain is often described ...

postherpetic neuralgia Postherpetic neuralgia (PHN) is neuropathic pain that occurs due to damage to a peripheral nerve caused by the reactivation of the varicella zoster virus (herpes zoster, also known as shingles). Typically, the nerve pain (neuralgia) is confined ...

and referred pain for

radiculopathy Radiculopathy, also commonly referred to as pinched nerve, refers to a set of conditions in which one or more nerves are affected and do not work properly (a neuropathy). Radiculopathy can result in pain ( radicular pain), weakness, altered sen ...

, in the form of a cream, ointment, liquid, spray, or gel, which may also contain

ketamine Ketamine is a dissociative anesthetic used medically for induction and maintenance of anesthesia. It is also used as a recreational drug. It is one of the safest anesthetics, as, in contrast with opiates, ether, and propofol, it suppress ...

and

lidocaine Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic of the amino amide type. It is also used to treat ventricular tachycardia. When used for local anaesthesia or in nerve blocks, lid ...

, along with other agents which may be useful, such as

cyclobenzaprine Cyclobenzaprine (sold under the brand name Flexeril, among others) is a medication used for muscle spasms from musculoskeletal conditions of sudden onset. It is not useful in cerebral palsy. It is taken by mouth. Use is not recommended for mor ...

amitriptyline Amitriptyline, sold under the brand name Elavil among others, is a tricyclic antidepressant primarily used to treat cyclic vomiting syndrome (CVS), major depressive disorder and a variety of pain syndromes from neuropathic pain to fibromyalgi ...

, acyclovir,

gabapentin Gabapentin, sold under the brand name Neurontin among others, is an anticonvulsant medication primarily used to treat partial seizures and neuropathic pain. It is a first-line medication for the treatment of neuropathic pain caused by diabeti ...

orphenadrine Orphenadrine (sold under many brand names) is an anticholinergic drug of the ethanolamine antihistamine class; it is closely related to diphenhydramine. It is a muscle relaxant that is used to treat muscle pain and to help with motor control i ...

and other drugs used as NSAIDs or adjuvant, atypical or potentiators for pain treatment. Trial is been going on for using this drug along with

ibuprofen Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used for treating pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus ar ...

for management of lymphedema . Animal trial and some human trials has been shown significant improvement over placebo control. Dr Stanley G Rockson, of

Stanford University Stanford University, officially Leland Stanford Junior University, is a private research university in Stanford, California. The campus occupies , among the largest in the United States, and enrolls over 17,000 students. Stanford is conside ...

is leading these researches.

Efficacy

A 2013

systematic review A systematic review is a scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from published studies on t ...

indicated "The efficacy of orally administered ketoprofen in relieving moderate-severe pain and improving functional status and general condition was significantly better than that of

and/or

diclofenac Diclofenac, sold under the brand name Voltaren, among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain and inflammatory diseases such as gout. It is taken by mouth or rectally in a suppository, used by injection, or ...

." A 2017 Cochrane systematic review investigating ketoprofen as a single-dose by mouth in acute, moderate-to-severe postoperative pain concluded that its efficacy is equivalent to drugs such as ibuprofen and diclofenac. There is evidence supporting topical ketoprofen for osteoarthritis but not other chronic musculoskeletal pain.

Adverse effects

In October 2020, the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(FDA) required the drug label to be updated for all nonsteroidal anti-inflammatory medications to describe the risk of kidney problems in fetuses that result in low amniotic fluid. They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy.

Mechanism

Ketoprofen undergoes metabolism in the liver via conjugation with

glucuronic acid Glucuronic acid (from Greek γλεῦκος "''wine, must''" and οὖρον "''urine''") is a uronic acid that was first isolated from urine (hence the name). It is found in many gums such as gum arabic (c. 18%), xanthan, and kombucha tea ...

(

glucuronidation Glucuronidation is often involved in drug metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve gl ...

) by UGT enzymes, hydroxylation of the benzoyl ring by the

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules ( xenobiotics), such as toxins or drugs, so that they can be removed from ...

and

CYP2C9 Cytochrome P450 family 2 subfamily C member 9 (abbreviated CYP2C9) is an enzyme protein. The enzyme is involved in metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, the pro ...

enzymes, and reduction of its

ketone In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double b ...

moiety Moiety may refer to: Chemistry * Moiety (chemistry), a part or functional group of a molecule ** Moiety conservation, conservation of a subgroup in a chemical species Anthropology * Moiety (kinship), either of two groups into which a society is ...

(a carbonyl

functional group In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the r ...

, i.e. with carbon-oxygen double bond) by carbonyl reducing enzymes (CREs).Ketoprofen. (n.d.). Millennium Web Catalog. Retrieved February 1, 2010, from http://0-online.lexi.com.library.touro.edu Ketoprofen is used for its antipyretic, analgesic, and anti-inflammatory properties by inhibiting cyclooxygenase-1 and -2 (COX-1 and COX-2) enzymes reversibly, which decreases production of proinflammatory prostaglandin precursors. The patches have been shown to provide rapid and sustained delivery to underlying tissues without significantly increasing levels of drug concentration in the blood when compared to the traditional oral administration.

Chirality and biological activity

Ketoprofen has one stereogenic center in the side chain and hence exists as mirror-image twins. Majority of the profens are marketed as racemic mixtures. For most of the NSAIDs the pharmacological activity reside in the (S)-enantiomers with their (R)-enantiomer of virtually inactive. An interesting observation about most profens including ketoprofen is that they undergo unidirectional metabolic inversion,

chiral inversion Chiral inversion is the process of conversion of one enantiomer of a chiral molecule to its mirror-image version with no other change in the molecule. Chiral inversion happens depending on various factors (viz. biological-, solvent-, light-, temper ...

, of the (R)- acid to its (S)-mirror-image version with no other change in the molecule.

Available forms

Ketoprofen was available

over-the-counter Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid prescr ...

in the United States in the form of 12.5 mg coated tablets (Orudis KT and Actron), but this form has been discontinued. It is available by prescription capsules. Ketoprofen is also available as a 2.5%

gel A gel is a semi-solid that can have properties ranging from soft and weak to hard and tough. Gels are defined as a substantially dilute cross-linked system, which exhibits no flow when in the steady-state, although the liquid phase may still di ...

for

topical A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes ...

application, and it is also available as a patch for topical analgesia and anti-inflammatory action. However, the gel is not sold in the United States. Brand names in Australia are Orudis and Oruvail. It is available in Japan in a transdermal patch Mohrus Tape, made by

Hisamitsu Pharmaceutical , headquartered in Saga and Tokyo, is a Japanese multinational pharmaceutical corporation that develops and markets prescription and over-the-counter drug (OTC) products, especially external pain relieving products such as the transdermal patc ...

. It is available in the UK as Ketoflam and Oruvail, in Ireland as Fastum Gel, in Estonia as Keto, Ketonal, and Fastum Gel, in Finland as Ketorin, Keto, Ketomex, and Orudis; in France as Profénid, Bi-Profénid, Toprec, and Ketum; in Italy as Ketodol, Fastum Gel, Lasonil, Orudis and Oki; in Poland as Ketonal, Ketonal active, Ketolek, in Serbia, Slovenia and Croatia as Knavon and Ketonal; in Romania as Ketonal and Fastum Gel; in Mexico as Arthril; in Norway as Zon and Orudis; in Russia as ОКИ (OKI), Fastum Gel and Ketonal; in Spain as Actron and Fastum Gel; in Albania as Oki and Fastum Gel and in Venezuela as Ketoprofeno as an injectable solution of 100 mg and 150 mg capsules. In some countries, the optically pure (''S'')-enantiomer ( dexketoprofen) is available; its trometamol salt is said to be particularly rapidly reabsorbed from the gastrointestinal tract, having a rapid onset of effects. The earliest report of therapeutic use in humans was in 1972.

Veterinary medicine

Ketoprofen is a common NSAID,

, and

used in horses and other equines. It is most commonly used for musculoskeletal pain, joint problems, and soft tissue injury, as well as

laminitis Laminitis is a disease that affects the feet of ungulates and is found mostly in horses and cattle. Clinical signs include foot tenderness progressing to inability to walk, increased digital pulses, and increased temperature in the hooves. Seve ...

. It is also used to control fevers and prevent

endotoxemia Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer m ...

. It is also used as a mild painkiller in smaller animals, generally following surgical procedures. In horses, it is given at a dose of 2.2 mg/kg/day. Studies have shown that it does not inhibit

5-lipoxygenase Arachidonate 5-lipoxygenase, also known as ALOX5, 5-lipoxygenase, 5-LOX, or 5-LO, is a non-heme iron-containing enzyme (EC 1.13.11.34) that in humans is encoded by the ''ALOX5'' gene. Arachidonate 5-lipoxygenase is a member of the lipoxygenase fa ...

and leukotriene B4, as originally claimed. It is therefore not considered superior to

phenylbutazone Phenylbutazone, often referred to as "bute", is a nonsteroidal anti-inflammatory drug (NSAID) for the short-term treatment of pain and fever in animals. In the United States and United Kingdom, it is no longer approved for human use (except in th ...

as previously believed, although clinical signs of lameness are reduced with its use. In fact, phenylbutazone was shown superior to ketoprofen in cases of experimentally-induced synovitis when both drugs were used at labeled dosages.Owens JG, Kamerling SG, Stanton SR, et al. Effects of pretreatment with ketoprofen and phenylbutazone on experi- mentally induced synovitis in dogs. 866 – 872.

Administration

Ketoprofen, when administered

intravenously Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...

, is recommended for a maximum of five days of use. Its analgesic and antipyretic effects begin to occur one to two hours following administration. The most common dosage is 1 mg/ lb, once per day, although this dosage may be lowered for ponies, which are most susceptible to NSAID side effects. It is also available as a capsule dosage form and tablet.

Ecological problems

Experiments have found ketoprofen, like

, is a veterinary drug causing lethal effects in

red-headed vulture The red-headed vulture (''Sarcogyps calvus''), also known as the Asian king vulture, Indian black vulture or Pondicherry vulture, is an Old World vulture mainly found in the Indian subcontinent, with small disjunct populations in some parts of So ...

s. Vultures feeding on the carcasses of recently treated livestock develop acute kidney failure within days of exposure.

References

External links

* {{Authority control Nonsteroidal anti-inflammatory drugs Equine medications Benzophenones Hepatotoxins