Acemetacin: Difference between revisions

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== Medical uses ==
== Medical uses ==
Acemetacin has proven effective in the treatment of osteoarthritis, rheumatoid arthritis, [[ankylosing spondylitis]], and other kinds of rheumathoid inflammation, as well as in post-operative and post-traumatic pain and attack of [[gout]].<ref name="AC" /><ref name="Dinnendahl" />
Acemetacin has proven effective in the treatment of osteoarthritis, rheumatoid arthritis, [[ankylosing spondylitis]], and other kinds of rheumathoid inflammation, as well as in post-operative and post-traumatic pain and attack of [[gout]].<ref name="AC" /><ref name="Dinnendahl" /> Application of a single dose of acemetacin for post-operative pain is not well supported by studies.<ref>{{cite journal|pmid=19588437}}</ref>


== Contraindications ==
== Contraindications ==
Line 79: Line 79:
== Pharmacology ==
== Pharmacology ==
{{main article|Non-steroidal anti-inflammatory drug#Mechanism of action}}
{{main article|Non-steroidal anti-inflammatory drug#Mechanism of action}}
Acemetacin, a [[glycolic acid]] [[ester]] of [[indometacin]], acts as an inhibitor of [[cyclooxygenase]] (COX), producing the anti-inflammatory and [[analgetic]] (pain relieving) effects. In the body, it is partly metabolized to indometacin, which also acts as a COX inhibitor. The same mechanism is responsible for the [[antipyretic]] and [[Antiplatelet drug|antiplatelet]] effects, which are however not clinically used, as well as for the typical NDAID adverse effects.<ref name="AC">{{cite book|title=Austria-Codex|editor=Haberfeld, H|publisher=Österreichischer Apothekerverlag|location=Vienna|year=2015|language=German}}</ref><ref name="Dinnendahl">{{cite book|title=Arzneistoff-Profile|editor1=Dinnendahl, V |editor2=Fricke, U |publisher=Govi Pharmazeutischer Verlag|location=Eschborn, Germany|date=2003|edition=18|volume=1|isbn=978-3-7741-9846-3|language=German}}</ref> An advantage of acemetacin is that it reduces gastric damage when compared to indometacin.{{fact|date=September 2016}}
Acemetacin, a [[glycolic acid]] [[ester]] of [[indometacin]], acts as an inhibitor of [[cyclooxygenase]] (COX), producing the anti-inflammatory and [[analgetic]] (pain relieving) effects. In the body, it is partly metabolized to indometacin, which also acts as a COX inhibitor. The same mechanism is responsible for the [[antipyretic]] and [[Antiplatelet drug|antiplatelet]] effects, which are however not clinically used, as well as for the typical NDAID adverse effects.<ref name="AC">{{cite book|title=Austria-Codex|editor=Haberfeld, H|publisher=Österreichischer Apothekerverlag|location=Vienna|year=2015|language=German}}</ref><ref name="Dinnendahl">{{cite book|title=Arzneistoff-Profile|editor1=Dinnendahl, V |editor2=Fricke, U |publisher=Govi Pharmazeutischer Verlag|location=Eschborn, Germany|date=2003|edition=18|volume=1|isbn=978-3-7741-9846-3|language=German}}</ref>

An advantage of acemetacin is that it reduces gastric damage as compared to indometacin, possibly because acemetacin has less effect on the increase of [[leukotriene B4]] synthesis and [[tumor necrosis factor]] (TNF) expression, leading to less induction of [[leukocyte]]-endothelial adherence.<ref>{{cite journal|pmid=17876306}}</ref><ref>{{cite journal|pmid=18695646}}</ref>


=== Pharmacokinetics ===
=== Pharmacokinetics ===
[[File:Acemetacin metabolism.svg|thumb|left|Metabolism of acemetacin. Cleaving of the glycolic acid ester (green) activates the substance to indometacin, cleaving of the methoxy ether or the chlorobenzoate (orange) inactivate it.]]
[[File:Acemetacin metabolism.svg|thumb|left|Metabolism of acemetacin. Cleaving of the glycolic acid ester (green) activates the substance to indometacin, cleaving of the methoxy ether or the 4-chlorobenzoate (orange) inactivate it.]]


The substance is quickly and almost completely absorbed from the gut. Highest [[blood plasma]] concentrations are reached after two hours. It is bound to [[plasma protein]]s to 80–90%.<ref name="AC" />
The substance is quickly and almost completely absorbed from the gut. Highest [[blood plasma]] concentrations are reached after two hours. It is bound to [[plasma protein]]s to 80–90%.<ref name="AC" />


Apart from the active [[metabolite]] indometacin, a number of inactive metabolites are found after application of acemetacin: the O-desmethyl-, deschlorobenzoyl-, and O-desmethyl-deschlorobenzoyl-derivatives of both indometacin and acemetacin, as well as all of these substances' [[glucuronide]]s. [[Elimination half-life]] is 4.5±2.8 hours (in some individuals up to 16 hours) under [[steady state]] conditions. 40% are eliminated via the kidney, and 50% vie the faeces.<ref name="AC" /><ref name="Dinnendahl" />
Apart from the active [[metabolite]] indometacin, a number of inactive metabolites are found after application of acemetacin: the O-desmethyl-, des-4-chlorobenzoyl-, and O-desmethyl-des-4-chlorobenzoyl derivatives of both indometacin and acemetacin, as well as all of these substances' [[glucuronide]]s. [[Elimination half-life]] is 4.5±2.8 hours (in some individuals up to 16 hours) under [[steady state]] conditions. 40% are eliminated via the kidney, and 50% vie the faeces.<ref name="AC" /><ref name="Dinnendahl" />


== Chemistry ==
== Chemistry ==

Revision as of 11:35, 16 September 2016

Acemetacin
Clinical data
Trade namesEmflex, many others
AHFS/Drugs.comInternational Drug Names
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • UK: POM (Prescription only)
Pharmacokinetic data
Bioavailability~100%
Protein binding80–90%
Elimination half-life4.5±2.8 hrs
Excretion40% renal, 50% biliary
Identifiers
  • 2-[2-[1-(4-Chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetyl]oxyacetic acid
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.053.077 Edit this at Wikidata
Chemical and physical data
FormulaC21H18ClNO6
Molar mass415.82372 g/mol g·mol−1
3D model (JSmol)
Melting point150 to 153 °C (302 to 307 °F)
  • Clc1ccc(cc1)C(=O)n3c2ccc(OC)cc2c(c3C)CC(=O)OCC(=O)O
  • InChI=1S/C21H18ClNO6/c1-12-16(10-20(26)29-11-19(24)25)17-9-15(28-2)7-8-18(17)23(12)21(27)13-3-5-14(22)6-4-13/h3-9H,10-11H2,1-2H3,(H,24,25) checkY
  • Key:FSQKKOOTNAMONP-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

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 as a prescription-only drug.[1]

Medical uses

Acemetacin has proven effective in the treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and other kinds of rheumathoid inflammation, as well as in post-operative and post-traumatic pain and attack of gout.[2][3] Application of a single dose of acemetacin for post-operative pain is not well supported by studies.[4]

Contraindications

Contraindications are basically the same as with other NSAIDs: hypersensitivity reactions to NSAIDs in the past (typically asthma or skin reactions), gastrointestinal or cerebral bleeding, peptic ulcer, haematopoietic disorders, and during the third trimester of pregnancy.[2][5]

Interactions

The following interactions, typical of NSAIDs, have been described:[2][3]

Pharmacology

Main article: Non-steroidal anti-inflammatory drug § Mechanism of action

Acemetacin, a glycolic acid ester of indometacin, acts as an inhibitor of cyclooxygenase (COX), producing the anti-inflammatory and analgetic (pain relieving) effects. In the body, it is partly metabolized to indometacin, which also acts as a COX inhibitor. The same mechanism is responsible for the antipyretic and antiplatelet effects, which are however not clinically used, as well as for the typical NDAID adverse effects.[2][3]

An advantage of acemetacin is that it reduces gastric damage as compared to indometacin, possibly because acemetacin has less effect on the increase of leukotriene B4 synthesis and tumor necrosis factor (TNF) expression, leading to less induction of leukocyte-endothelial adherence.[6][7]

Pharmacokinetics

Metabolism of acemetacin. Cleaving of the glycolic acid ester (green) activates the substance to indometacin, cleaving of the methoxy ether or the 4-chlorobenzoate (orange) inactivate it.

The substance is quickly and almost completely absorbed from the gut. Highest blood plasma concentrations are reached after two hours. It is bound to plasma proteins to 80–90%.[2]

Apart from the active metabolite indometacin, a number of inactive metabolites are found after application of acemetacin: the O-desmethyl-, des-4-chlorobenzoyl-, and O-desmethyl-des-4-chlorobenzoyl derivatives of both indometacin and acemetacin, as well as all of these substances' glucuronides. Elimination half-life is 4.5±2.8 hours (in some individuals up to 16 hours) under steady state conditions. 40% are eliminated via the kidney, and 50% vie the faeces.[2][3]

Chemistry

Acemetacin is a fine, slightly yellowish, crystalline powder that melts at 150 to 153 °C (302 to 307 °F). It is polymorphic, with four known anhydrous (water-free) and two monohydrate crystalline forms.[3]

Society and culture

Brand names

Other brand names for acemetacin include Zadex (Hungary), Rheutrop (Austria), Acemetadoc, Acephlogont, Azeat, Rantudil (Germany, Hungary, Mexico, Portugal, Turkey), Gamespir (Greece), Oldan, Reudol (Spain), Tilur (Switzerland), Ost-map (Egypt).

References

  1. ^ International Drug Names: Acemetacin.
  2. ^ a b c d e f Haberfeld, H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.
  3. ^ a b c d e Dinnendahl, V; Fricke, U, eds. (2003). Arzneistoff-Profile (in German). Vol. 1 (18 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3.
  4. ^ . PMID 19588437. {{cite journal}}: Cite journal requires |journal= (help); Missing or empty |title= (help)
  5. ^ UK Drug Information on Emflex.
  6. ^ . PMID 17876306. {{cite journal}}: Cite journal requires |journal= (help); Missing or empty |title= (help)
  7. ^ . PMID 18695646. {{cite journal}}: Cite journal requires |journal= (help); Missing or empty |title= (help)
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