Ketoprofen

Ketoprofen is one of the propionic acid class of nonsteroidal anti-inflammatory drugs (NSAID) with analgesic and antipyretic effects. It acts by inhibiting the body's production of prostaglandin.

Ketoprofen

Clinical data
Trade names	Oruvail, others
AHFS/Drugs.com	Monograph
MedlinePlus	a686014
License data	US DailyMed: Ketoprofen
Pregnancy category	AU: C
Routes of administration	By mouth, topical, intravenous
ATC code	M01AE03 (WHO) M01AE53 (WHO), M02AA10 (WHO)
Legal status
Legal status	AU: S3 (Pharmacist only) / S4 CA: ℞-only US: WARNINGRx-only Rx-only & OTC
Pharmacokinetic data
Protein binding	99%
Elimination half-life	2–2.5 hours
Identifiers
IUPAC name (RS)-2-(3-benzoylphenyl)propanoic acid
CAS Number	22071-15-4 Y
PubChem CID	3825
IUPHAR/BPS	4795
DrugBank	DB01009 Y
ChemSpider	3693 Y
UNII	90Y4QC304K
KEGG	D00132 Y
ChEBI	CHEBI:6128 N
ChEMBL	ChEMBL571 Y
CompTox Dashboard (EPA)	DTXSID6020771
ECHA InfoCard	100.040.676
Chemical and physical data
Formula	C16H14O3
Molar mass	254.285 g·mol−1
3D model (JSmol)	Interactive image
Chirality	Racemic mixture
SMILES CC(c1cccc(c1)C(=O)c2ccccc2)C(=O)O
InChI InChI=1S/C16H14O3/c1-11(16(18)19)13-8-5-9-14(10-13)15(17)12-6-3-2-4-7-12/h2-11H,1H3,(H,18,19) Y Key:DKYWVDODHFEZIM-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

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, postherpetic neuralgia and referred pain for radiculopathy, in the form of a cream, ointment, liquid, spray, or gel, which may also contain ketamine and lidocaine, along with other agents which may be useful, such as cyclobenzaprine, amitriptyline, acyclovir, gabapentin, orphenadrine and other drugs used as NSAIDs or adjuvant, atypical or potentiators for pain treatment.

Trials are going on for using this drug along with ibuprofen for management of lymphedema. Animal trial and some human trials have shown significant improvement over placebo control. Dr Stanley G Rockson, of Stanford University is leading these researches.

Efficacy

A 2013 systematic review 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 ibuprofen and/or diclofenac." 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 (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 (glucuronidation) by UGT enzymes, hydroxylation of the benzoyl ring by the CYP3A4 and CYP2C9 enzymes, and reduction of its ketone moiety (a carbonyl functional group, i.e. with carbon-oxygen double bond) by carbonyl reducing enzymes (CREs). 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 resides in the (S)-enantiomers with their (R)-enantiomer virtually inactive. An interesting observation about most profens including ketoprofen is that they undergo unidirectional metabolic inversion, chiral inversion, of the (R)- acid to its (S)-mirror-image version with no other change in the molecule. There have been concerns raised that Ketoprofen can break down into the parent benzophenone molecule in skin exposed to strong summer or tropical UV light and this could pose a theoretical cancer risk. Given such a risk it is better to use other pain killers in such circumstances.

History

The earliest report of therapeutic use in humans is in 1972.

Society and culture

Brand names

Brand names in Australia include Orudis and Oruvail. It is available in Japan in a transdermal patch Mohrus Tape, made by Hisamitsu Pharmaceutical. 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 Greece as Okitask; 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.

Veterinary medicine

Ketoprofen is a common NSAID, antipyretic, and analgesic used in horses and other equines. It is most commonly used for musculoskeletal pain, joint problems, and soft tissue injury, as well as laminitis. It is also used to control fevers and prevent endotoxemia. 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 and leukotriene B4, as originally claimed. It is therefore not considered superior to phenylbutazone 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.

Ecological problems

See also: Indian vulture crisis

Experiments have found ketoprofen, like diclofenac, is a veterinary drug causing lethal effects in red-headed vultures. Vultures feeding on the carcasses of recently treated livestock develop acute kidney failure within days of exposure.