Nabumetone

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Nabumetone
Nabumetone.svg
Clinical data
AHFS/Drugs.com Monograph
MedlinePlus a692022
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
Pharmacokinetic data
Protein binding > 99% (active metabolite)
Metabolism Liver, to active metabolite 6-methoxy-2-naphthylacetic acid; 6-MNA
Elimination half-life 23 hours (active metabolite)
Excretion Kidney
Identifiers
  • 4-(6-methoxy-2-naphthyl)-2-butanone
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.169.752 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C15H16O2
Molar mass 228.291 g·mol−1
3D model (JSmol)
  • O=C(C)CCc1ccc2c(c1)ccc(OC)c2
  • InChI=1S/C15H16O2/c1-11(16)3-4-12-5-6-14-10-15(17-2)8-7-13(14)9-12/h5-10H,3-4H2,1-2H3 Yes check.svgY
  • Key:BLXXJMDCKKHMKV-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)
Three step CYP1A2 Mediated Metabolism of the prodrug Nabumetone to its active metabolite 6-MNA. Nabumetone Metabolism.gif
Three step CYP1A2 Mediated Metabolism of the prodrug Nabumetone to its active metabolite 6-MNA.

Nabumetone is a nonsteroidal anti-inflammatory drug (NSAID). [2] Nabumetone was developed by Beecham and first received regulatory approval in 1991. [3] It is available under numerous brand names, such as Relafen, Relifex, and Gambaran.

Contents

Nabumetone is a non-acidic NSAID prodrug that is rapidly metabolized in the liver to the active metabolite, 6-methoxy-2-naphthyl acetic acid. Nabumetone's active metabolite inhibits the cyclooxygenase enzyme and preferentially blocks COX-2 activity (which is indirectly responsible for the production of inflammation and pain during arthritis). The active metabolite of nabumetone is felt to be the compound primarily responsible for therapeutic effect. Comparatively, the parent drug is a poor inhibitor of COX-2 byproducts, particularly prostaglandins. It may be less nephrotoxic than indomethacin. [4] There are two known polymorphs of the compound. [5]

Nabumetone has little effect on renal prostaglandin secretion and less of an association with heart failure than other traditional drugs of the class. [6] Effects of nabumetone on blood pressure control in hypertensive patients on ACE inhibitors are also good,[ clarification needed ] equivalent to paracetamol. [7]

Medical uses

Nabumetone is used to treat pain and inflammation.[ citation needed ]

Side effects

It has been shown to have a slightly lower risk of gastrointestinal side effects than most other nonselective NSAIDs, since it is a non-acidic prodrug that is metabolized to its active 6-MNA (6-methoxy-2-naphthylacetic acid) form.[ citation needed ]

Side effects include bloody or black, tarry stools; change in color, frequency, or amount of urine; chest pain; shortness of breath; coughing up blood; pale stools; numbness; weakness; flu-like symptoms; leg pain; vision problems; speech problems; problems walking; weight gain; stomach pain; cold sweat; skin rash; blisters; headache; swelling; bleeding; bruising; vomiting blood; jaundice; diarrhea; constipation; dizziness; indigestion; gas; nausea; and ringing in the ears. [8]

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 unborn babies that result in low amniotic fluid. [9] [10] They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy. [9] [10]

Related Research Articles

<span class="mw-page-title-main">Ketoprofen</span> NSAID analgesic medication

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.

<span class="mw-page-title-main">Nonsteroidal anti-inflammatory drug</span> Class of therapeutic drug for relieving pain and inflammation

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 of use, but largely include an increased risk of gastrointestinal ulcers and bleeds, heart attack, and kidney disease.

<span class="mw-page-title-main">Ibuprofen</span> Medication used for treating pain, fever, and inflammation

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used to relieve pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus arteriosus in a premature baby. It can be used orally or intravenously. It typically begins working within an hour.

<span class="mw-page-title-main">Cyclooxygenase</span> Class of enzymes

Cyclooxygenase (COX), officially known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme that is responsible for biosynthesis of prostanoids, including thromboxane and prostaglandins such as prostacyclin, from arachidonic acid. A member of the animal-type heme peroxidase family, it is also known as prostaglandin G/H synthase. The specific reaction catalyzed is the conversion from arachidonic acid to prostaglandin H2 via a short-living prostaglandin G2 intermediate.

<span class="mw-page-title-main">Diclofenac</span> Nonsteroidal anti-inflammatory drug

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 applied to the skin. Improvements in pain last for as much as eight hours. It is also available in combination with misoprostol in an effort to decrease stomach problems.

<span class="mw-page-title-main">Naproxen</span> Nonsteroidal anti-inflammatory drug (NSAID) used to treat pain

Naproxen, sold under the brand name Aleve among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain, menstrual cramps, inflammatory diseases such as rheumatoid arthritis, gout and fever. It is taken orally. It is available in immediate and delayed release formulations. Onset of effects is within an hour and lasts for up to twelve hours.

<span class="mw-page-title-main">Indometacin</span> Anti-inflammatory drug

Indometacin, also known as indomethacin, is a nonsteroidal anti-inflammatory drug (NSAID) commonly used as a prescription medication to reduce fever, pain, stiffness, and swelling from inflammation. It works by inhibiting the production of prostaglandins, endogenous signaling molecules known to cause these symptoms. It does this by inhibiting cyclooxygenase, an enzyme that catalyzes the production of prostaglandins.

<span class="mw-page-title-main">Mefenamic acid</span> Chemical compound

Mefenamic acid is a member of the anthranilic acid derivatives class of nonsteroidal anti-inflammatory drugs (NSAIDs), and is used to treat mild to moderate pain.

<span class="mw-page-title-main">Meloxicam</span> Nonsteroidal anti-inflammatory drug (NSAID)

Meloxicam, sold under the brand name Mobic among others, is a nonsteroidal anti-inflammatory medication (NSAID) used to treat pain and inflammation in rheumatic diseases and osteoarthritis. It is used by mouth or by injection into a vein. It is recommended that it be used for as short a period as possible and at a low dose.

<span class="mw-page-title-main">Etodolac</span> Nonsteroidal anti-inflammatory drug

Etodolac is a nonsteroidal anti-inflammatory drug (NSAID).

<span class="mw-page-title-main">Diflunisal</span> NSAID analgesic and anti-inflammatory drug

Diflunisal is a salicylic acid derivative with analgesic and anti-inflammatory activity. It was developed by Merck Sharp & Dohme in 1971, as MK647, after showing promise in a research project studying more potent chemical analogs of aspirin. It was first sold under the brand name Dolobid, marketed by Merck & Co., but generic versions are now widely available. It is classed as a nonsteroidal anti-inflammatory drug (NSAID) and is available in 250 mg and 500 mg tablets.

<span class="mw-page-title-main">Flurbiprofen</span> Chemical compound

Flurbiprofen is a member of the phenylalkanoic acid derivative family of nonsteroidal anti-inflammatory drugs (NSAIDs). It is primarily indicated as a pre-operative anti-miotic as well as orally for arthritis or dental pain. Side effects are analogous to those of ibuprofen.

<span class="mw-page-title-main">Sulindac</span> Nonsteroidal anti-inflammatory drug (NSAID)

Sulindac is a nonsteroidal anti-inflammatory drug (NSAID) of the arylalkanoic acid class that is marketed as Clinoril. Imbaral is another name for this drug. Its name is derived from sul(finyl)+ ind(ene)+ ac(etic acid) It was patented in 1969 and approved for medical use in 1976.

<span class="mw-page-title-main">Tolmetin</span> NSAID analgesic medication

Tolmetin is a nonsteroidal anti-inflammatory drug (NSAID) of the heterocyclic acetic acid derivative class.

<span class="mw-page-title-main">Meclofenamic acid</span> Chemical compound

Meclofenamic acid is a drug used for joint, muscular pain, arthritis and dysmenorrhea. It is a member of the anthranilic acid derivatives class of nonsteroidal anti-inflammatory drugs (NSAIDs) and was approved by the US FDA in 1980. Like other members of the class, it is a cyclooxygenase (COX) inhibitor, preventing the formation of prostaglandins.

<span class="mw-page-title-main">Fenoprofen</span> NSAID analgesic and anti-inflammatory drug

Fenoprofen, sold under the brand name Nalfon among others, is a nonsteroidal anti-inflammatory drug (NSAID). Fenoprofen calcium is used for symptomatic relief for rheumatoid arthritis, osteoarthritis, and mild to moderate pain. It has also been used to treat postoperative pain. It is available as a generic medication.

<span class="mw-page-title-main">Acemetacin</span> NSAID analgesic medication

Acemetacin is a non-steroidal anti-inflammatory drug (NSAID) used for the treatment of osteoarthritis, rheumatoid arthritis, lower back pain, and relieving post-operative pain. It is manufactured by Merck KGaA under the tradename Emflex, and is available in the UK and other countries as a prescription-only drug.

<span class="mw-page-title-main">Bromfenac</span> Chemical compound

Bromfenac is a nonsteroidal anti-inflammatory drug (NSAID) marketed in the US as an ophthalmic solution by ISTA Pharmaceuticals for short-term, local use. Prolensa and Bromday are the once-daily formulation of bromfenac, while Xibrom was approved for twice-daily administration. In the European Union, the brand name is Yellox. Bromfenac is indicated for the treatment of ocular inflammation and pain after cataract surgery.

Cyclooxygenases are enzymes that take part in a complex biosynthetic cascade that results in the conversion of polyunsaturated fatty acids to prostaglandins and thromboxane(s). Their main role is to catalyze the transformation of arachidonic acid into the intermediate prostaglandin H2, which is the precursor of a variety of prostanoids with diverse and potent biological actions. Cyclooxygenases have two main isoforms that are called COX-1 and COX-2. COX-1 is responsible for the synthesis of prostaglandin and thromboxane in many types of cells, including the gastro-intestinal tract and blood platelets. COX-2 plays a major role in prostaglandin biosynthesis in inflammatory cells and in the central nervous system. Prostaglandin synthesis in these sites is a key factor in the development of inflammation and hyperalgesia. COX-2 inhibitors have analgesic and anti-inflammatory activity by blocking the transformation of arachidonic acid into prostaglandin H2 selectively.

Prostaglandin inhibitors are drugs that inhibit the synthesis of prostaglandin in human body. There are various types of prostaglandins responsible for different physiological reactions such as maintaining the blood flow in stomach and kidney, regulating the contraction of involuntary muscles and blood vessels, and act as a mediator of inflammation and pain. Cyclooxygenase (COX) and Phospholipase A2 are the major enzymes involved in prostaglandin production, and they are the drug targets for prostaglandin inhibitors. There are mainly 2 classes of prostaglandin inhibitors, namely non- steroidal anti- inflammatory drugs (NSAIDs) and glucocorticoids. In the following sections, the medical uses, side effects, contraindications, toxicity and the pharmacology of these prostaglandin inhibitors will be discussed.

References

  1. ↑ Varfaj F, Zulkifli SN, Park HG, Challinor VL, De Voss JJ, Ortiz de Montellano PR (May 2014). "Carbon-carbon bond cleavage in activation of the prodrug nabumetone". Drug Metabolism and Disposition. 42 (5): 828–838. doi:10.1124/dmd.114.056903. PMC   3989788 . PMID   24584631.
  2. ↑ Gonzalo-Garijo MA, Cordobés-Duran C, Lamilla-Yerga AM, Moreno-Gastón I (2007). "Severe immediate reaction to nabumetone". Journal of Investigational Allergology & Clinical Immunology. 17 (4): 274–276. PMID   17694703.
  3. ↑ "Nabumetone Page". RCSB Protein Data Bank. Retrieved 5 August 2021.
  4. ↑ Olsen NV, Jensen NG, Hansen JM, Christensen NJ, Fogh-Andersen N, Kanstrup IL (October 1999). "Non-steroidal anti-inflammatory drugs and renal response to exercise: a comparison of indomethacin and nabumetone". Clinical Science. 97 (4): 457–465. doi:10.1042/cs0970457. PMID   10491346. S2CID   33526598.
  5. ↑ Price CP, Grzesiak AL, Lang M, Matzger AJ (2002). "Polymorphism of Nabumetone". Crystal Growth & Design. 2 (6): 501–503. doi:10.1021/cg0255568.
  6. ↑ Donnan PT (2000). "098. A Drug-Safety Study to Examine the Possible Association of Congestive Heart Failure with Dispensed Nabumetone, Ibuprofen and other Non-Steroidal Anti-inflammatory Drugs". Pharmacoepidemiology and Drug Safety. 8 (S2): S115. doi:10.1002/(SICI)1099-1557(199908)8:2+<S79::AID-PDS429>3.0.CO;2-2.
  7. ↑ Palmer RH, Haig AE, Flavin SK, Iyengar MK (2001). "Effects of ibuprofen (IB), nabumetone (N) and celecoxib (C) on blood pressure (BP) control in hypertensive patients on ACE inhibitors". American Journal of Hypertension. 14 (S1): 85A. doi: 10.1016/S0895-7061(01)01811-8 .
  8. ↑ "Relafen (Nabumetone): Side Effects, Interactions, Warning, Dosage & Uses". RxList. Retrieved 9 March 2018.
  9. 1 2 "FDA Warns that Using a Type of Pain and Fever Medication in Second Half of Pregnancy Could Lead to Complications". U.S. Food and Drug Administration (FDA) (Press release). 15 October 2020. Retrieved 15 October 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  10. 1 2 "NSAIDs may cause rare kidney problems in unborn babies". U.S. Food and Drug Administration. 21 July 2017. Retrieved 15 October 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
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