Ketoprofen

Ketoprofen
Systematic (IUPAC) name
(RS)-2-(3-benzoylphenyl)propanoic acid
Clinical data
AHFS/Drugs.com monograph
MedlinePlus a686014
Pregnancy
category
  • C (D in 3rd trimester)
Routes of
administration		 Oral, topical, intravenous (veterinary use)
Legal status
Legal status
  • AU: S3 (Pharmacist only)
  • Prescription-only medicine
Pharmacokinetic data
Protein binding 99%
Biological half-life 2-2.5 hours
Identifiers
CAS Number 22071-15-4 YesY
ATC code M01AE03 (WHO) M01AE17 (WHO), M02AA10 (WHO)
PubChem CID 3825
IUPHAR/BPS 4795
DrugBank DB01009 YesY
ChemSpider 3693 YesY
UNII 90Y4QC304K YesY
KEGG D00132 YesY
ChEBI CHEBI:6128 N
ChEMBL CHEMBL571 YesY
Chemical data
Formula C16H14O3
Molar mass 254.281 g/mol
Chirality Racemic mixture
 NYesY (what is this?)  (verify)

Ketoprofen, (RS)2-(3-benzoylphenyl)-propionic acid (chemical formula C16H14O3) is one of the propionic acid class of nonsteroidal anti-inflammatory drugs (NSAID) with analgesic and antipyretic effects.[1] It acts by inhibiting the body's production of prostaglandin.

As of 2015 the cost for a typical month of medication in the United States is 50 to 100 USD.[2]

Available forms

Ketoprofen was available over-the-counter 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 as 50, 75, 100, 150, and 200 mg capsules.

Ketoprofen is also available as a 2.5% gel for topical 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. It is available in the UK as Ketoflam and Oruvail, in Estonia as Keto, Ketonal, and Fastum Gel, in Finland as Ketorin, Keto, Ketomex, and Orudis; in France as Profénid, Bi-Profénid and Ketum; in Italy as Ketodol, Fastum Gel, Lasonil, Orudis and Oki; in Poland, Serbia, Slovenia and Croatia as Knavon and Ketonal; in Romania as Ketonal; in Mexico as Arthril; in Norway as Zon and Orudis; in Russia as ОКИ (OKI), Fastum Gel and Ketonal; in Spain as Actron; and in Venezuela as Ketoprofeno under an injectable solution of 100 mg and 150 mg capsules.

In Lithuania, ketoprofen is called Ketoprofenum and Ketoprofenas. For topical application: the name brands are Fastum with 2.5% (gel) which is over the counter, and Ketospray with 10% (liquid spray), which must be prescribed. In Switzerland, an innovative ketoprofen formulation based on transfersome technology for direct application on the skin above the site to be treated has been approved.

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 [3]

Indication

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 extensively used for treatment of musculoskeletal pain.[4][5][6] 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.[6][7] Ketoprofen undergoes metabolism in the liver via conjugation with glucoronic acid, CYP3A4 and CYP2C9 hydroxylation of the benzoyl ring, and reduction of its keto function.[8][9] 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.[8][10]

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.

Efficacy

A systematic review and meta-analysis 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."[11] A Cochrane review investigating ketoprofen as a single-dose oral analgesic in acute, moderate-to-severe postoperative pain concluded that its efficacy is equivalent to drugs such as ibuprofen and diclofenac.[12] In particular, after dental surgery, doses >25 mg provide at least 50% pain relief to more than 60% of people treated, giving relief for about 5 hours.[12]

Uses with other drugs

Ketoprofen should not be used in combination with other NSAIDs or corticosteroids, as this increases the risk of gastrointestinal (GI) ulceration. It should also be used with caution with other anticoagulants. It is commonly used with omeprazole, sucralfate, and cimetidine to help protect the GI tract.

Use in horses and other animals

Ketoprofen is a common NSAID, antipyretic, and analgesic used in horses and other equines.[13] 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 2.2mg/kg/day. Studies have shown that it does not inhibit 5-lipoxygenase and leukotriene B4,[14] as originally claimed.[15] It is therefore not considered superior to phenylbutazone as previously believed, although clinical signs of lameness are reduced with its use.[16] In fact, phenylbutazone was shown superior to ketoprofen in cases of experimentally-induced synovitis when both drugs were used at labeled dosages.[17]

Administration

Ketoprofen, when administered intravenously, 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 a tablet.

Ecological problems

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 suffer acute kidney failure within days of exposure.[18]

References

  1. ↑ Kantor, T. G. (1986). "Ketoprofen: a review of its pharmacologic and clinical properties". Pharmacotherapy 6 (3): 93–103. doi:10.1002/j.1875-9114.1986.tb03459.x. PMID 3526298.
  2. ↑ Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 9. ISBN 9781284057560.
  3. ↑ A. N. Gyory, M. Bloch, H. C. Burry, R. Grahame; Bloch; Burry; Grahame (1972). "Orudis in Management of Rheumatoid Arthritis and Osteoarthrosis of the Hip: Comparison with Indomethacin". British Medical Journal 4 (5837): 398–400. doi:10.1136/bmj.4.5837.398. PMID 4564764.
  4. ↑ Mazières, B; Rouanet, S; Guillon, Y; Scarsi, C; Reiner, V (2005). "Topical ketoprofen patch in the treatment of tendinitis: a randomized, double blind, placebo controlled study.". The Journal of rheumatology 32 (8): 1563–70. PMID 16078335.
  5. ↑ Mazières, B (2005). "Topical ketoprofen patch.". Drugs in R&D 6 (6): 337–44. doi:10.2165/00126839-200506060-00003. PMID 16274258.
  6. 1 2 Sekiya, I; Morito, T; Hara, K; Yamazaki, J; Ju, YJ; Yagishita, K; Mochizuki, T; Tsuji, K; Muneta, T (2010). "Ketoprofen Absorption by Muscle and Tendon after Topical or Oral Administration in Patients Undergoing Anterior Cruciate Ligament Reconstruction". AAPS PharmSciTech 11 (1): 154–58. doi:10.1208/s12249-009-9367-2. PMC 2850498. PMID 20087696.
  7. ↑ Gayman, MD; Turner, RJ; Cui, M (2008). "Physical Limitations and Depressive Symptoms: Exploring the Nature of the Association". The journals of gerontology. Series B, Psychological sciences and social sciences 63 (4): S219–S228. doi:10.1093/geronb/63.4.s219. PMC 2844725. PMID 18689771.
  8. 1 2 Ketoprofen. (n.d.). Millennium Web Catalog. Retrieved February 1, 2010, from http://0-online.lexi.com.library.touro.edu
  9. ↑ Lemke TL, Williams DA, Roche VF, Zito SW. Foyes Principles of Medical Chemistry. 6th ed. Philadelphia: Lippincott Williams and Wilkins; 2008.
  10. ↑ Ketoprofen. (n.d.). Micromedex. Retrieved February 1, 2010, from https://bb-tuc.touro.edu/webapps/portal/frameset.jsp?tab_id=_102_1
  11. ↑ Sarzi-Puttini, P; Atzeni, F; Lanata, L; Bagnasco, M (2013). "Efficacy of ketoprofen vs. ibuprofen and diclofenac: a systematic review of the literature and meta-analysis". Clinical and experimental rheumatology 31 (5): 731–8. PMID 23711416.
  12. 1 2 Barden, J; Derry, S; McQuay, HJ; Moore, RA; McQuay, H. J.; Moore, R. A. (2009). "Single dose oral ketoprofen and dexketoprofen for acute postoperative pain in adults". The Cochrane database of systematic reviews (4): CD007355. doi:10.1002/14651858.CD007355.pub2. PMID 19821407.
  13. ↑ Forney, Barbara C, MS, VMD. Equine Medications, Revised Edition. Blood Horse Publications. Lexington, KY. Copyright 2007.
  14. ↑ Salman JA, Tilling LC, Monscada S. Benoxaprofen does not inhibit formation of leukotriene B4 in a model of acute inflammation. Biochem Pharmacol 1984;33:28–2930.
  15. ↑ Betley M, Sutherland SF, Gregoricka MJ, Pollett RA. The analgesic effect of ketoprofen for use in treating equine colic as compared to flunixin meglumine. Equine Pract 1991;13: 11–16.
  16. ↑ Owens JG, Kamerling SG, Keowen ML. Anti-inflammatory effects and pharmacokinetics of ketoprofen in a model of equine synovitis, in Proceedings. 6th Int Cong Eur Assoc Vet Pharmacol Toxicol 1994;170–171.
  17. ↑ Owens JG, Kamerling SG, Stanton SR, et al. Effects of pretreatment with ketoprofen and phenylbutazone on experi- mentally induced synovitis in dogs. 866 – 872.
  18. ↑ Naidoo.V, Wolter.K, Cromarty.D, Diekmann.M, Duncan.N, Meharg.A.A, Taggart.M.A, Venter.L, Cuthbert.R (2009). "Toxicity of non-steroidal anti-inflammatory drugs to Gyps vultures: a new threat from ketoprofen". Biology Letters 6 (3): 339–341. doi:10.1098/rsbl.2009.0818. ISSN 1744-9561.
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