Identification
- Summary
Acemetacin is a NSAID indicated in the treatment of pain and inflammation.
- Generic Name
- Acemetacin
- DrugBank Accession Number
- DB13783
- Background
Acemetacin is a carboxymethyl ester of indometacin. It is a potent non-steroidal anti-inflammatory drug, derived from the indol-3-acetic acid, whose activity is thought to be mainly through its active metabolite indomethacin.1 In clinical trials, acemetacin exhibits a better gastric tolerability compared to its active metabolite indometacin.6 It was developed by E. Merck and Company in Germany as an attempt to provide a safer drug but other than the amelioration on the gastrointestinal effects, the metabolism of acetamicin led to the formation of indomethacin and it kept the same side effects.7
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Acemetacin (DB13783)
- Weight
- Average: 415.83
Monoisotopic: 415.082265 - Chemical Formula
- C21H18ClNO6
- Synonyms
- Acemetacin
- Acemetacina
- Acemetacine
- Acemetacinum
- indometacin carboxymethyl ester
- indometacin glycolic ester
- indomethacin carboxymethyl ester
- indomethacin glycolic ester
- External IDs
- K 708
- K-708
- TV-1322
- TVX 3322
Pharmacology
- Indication
Acemetacin is not FDA, Canada or EMA approved, but in the countries where it is marketed it is indicated for the symptomatic treatment of pain and swelling in acute inflammation of the joints in rheumathoid arthritis, osteoarthritis, low back pain and post-surgical pain.11 It is also indicated for the treatment of chronic inflammation of the joints in presence of rheumatoid arthritis, treatment of ankylosing spondylitis, treatment of irritation in the joints and spinal column caused by degenerative disorders, treatment of inflammatory soft-tissue rheumatism syndrome and painful swelling and inflammation caused by injury.10,12
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Symptomatic treatment of Pain, inflammatory •••••••••••• ••••• - Contraindications & Blackbox Warnings
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The effect of acemetacin causes a weak reduction of prostaglandin synthesis which generates an anti-inflammatory and analgesic effect. The weak inhibition of prostaglandin reduces significantly the damage caused in the mucous membrane of the gastrointestinal tract. Studies have shown that acemetacin strongly inhibits the release of histamine from mast cells and the generation of hyperthermia. Acemetacin effect also causes changes in systolic and diastolic blood pressure as well as inhibition of platelet aggregation.2
- Mechanism of action
Acemetacin is a non-selective inhibitor of the production of pro-inflammatory mediators derived from the action of the enzyme COX. COX is essential for the synthesis of prostaglandin E2 and F2 which are molecules derived from fatty acids and stored in the cell membrane.8 Acetometacine is metabolized and forms its major metabolite indometacin which is also a non-selective inhibitor of COX and exhibits the capacity to inhibit the motility of polymorphonuclear leukocytes and decreased cerebral flow by modulating the nitric oxide pathway and vasoconstriction.7
Target Actions Organism AProstaglandin G/H synthase 1 antagonistHumans AProstaglandin G/H synthase 2 antagonistHumans - Absorption
After 8 days of oral administration twice daily of acemetacin there was an age-dependant Cmax of 276.8 ng/ml in elderly compared to 187 ng/ml for younger individuals. There was also a Tmax of 2.5 h and AUC in a range of 483-712 ng h/ml.3 The bioavailability of acemetacin after repeated doses is aproximately 66% in plasma and 64% in urine.4
- Volume of distribution
The apparent volume of distribution of acemetacin is in a range of 0.5-0.7 L/kg.9
- Protein binding
Acemetacin is found highly bound to plasma proteins, reaching a percentage higher than 90% of the administered dose.9
- Metabolism
Acemetacin is highly metabolized and degraded by esterolytic cleavage to form its major and active metabolite indometacin. It presents other inactive metabolites made by reaction of O-demethylation, N-desacylation and part of them are also transformed by conjugation with glucuronic acid.9
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- Route of elimination
The elimination of acemetacin is divided in renal elimination that covers 40% of the complete administered dose and the restant 60% is excreted in feces.9
- Half-life
The elimination half-life of acemetacin after steady-state is 4.5 hours.4
- Clearance
Intravenous administration of acemetacin in healthy subjects reported a clearance rate of 4.59 ml min/kg.5
- Adverse Effects
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The pharmacological activity of acemetacin causes blockage of prostaglandin synthesis. Prostaglandin is one of the mediators of renal blood flow and glomerular filtration thus, acemetacin causes a decreased renal function, transient renal insufficiency, interstitial nephritis and papillary necrosis especially in elderly patients, patients with congestive heart failure, hepatic cirrhosis and impaired renal function.9
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Acemetacin may decrease the excretion rate of Abacavir which could result in a higher serum level. Abciximab The risk or severity of bleeding and hemorrhage can be increased when Abciximab is combined with Acemetacin. Acebutolol Acemetacin may decrease the antihypertensive activities of Acebutolol. Aceclofenac The risk or severity of adverse effects can be increased when Aceclofenac is combined with Acemetacin. Acenocoumarol The risk or severity of bleeding and hemorrhage can be increased when Acenocoumarol is combined with Acemetacin. - Food Interactions
- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Acemix (Bioprogress) / Emflex (Merck Serono) / Rantudil (Bayer or Bial) / Solart (Bioindustria)
Categories
- ATC Codes
- M01AB11 — Acemetacin
- Drug Categories
- Acetic Acid Derivatives and Related Substances
- Agents causing hyperkalemia
- Agents that produce hypertension
- Analgesics
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Antigout Preparations
- Antiinflammatory and Antirheumatic Products
- Antiinflammatory and Antirheumatic Products, Non-Steroids
- Antirheumatic Agents
- Heterocyclic Compounds, Fused-Ring
- Indoles
- Musculo-Skeletal System
- Nephrotoxic agents
- Non COX-2 selective NSAIDS
- Peripheral Nervous System Agents
- Sensory System Agents
- UGT2B7 substrates
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as benzoylindoles. These are organic compounds containing an indole attached to a benzoyl moiety through the acyl group.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Indoles and derivatives
- Sub Class
- Benzoylindoles
- Direct Parent
- Benzoylindoles
- Alternative Parents
- Indole-3-acetic acid derivatives / Indolecarboxylic acids and derivatives / 3-alkylindoles / 4-halobenzoic acids and derivatives / Anisoles / Benzoyl derivatives / Alkyl aryl ethers / Chlorobenzenes / Dicarboxylic acids and derivatives / Aryl chlorides show 11 more
- Substituents
- 3-alkylindole / 4-halobenzoic acid or derivatives / Alkyl aryl ether / Anisole / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid / Benzoic acid or derivatives show 27 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- monocarboxylic acid, carboxylic ester, monochlorobenzenes, N-acylindole, indol-3-yl carboxylic acid (CHEBI:31162)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 5V141XK28X
- CAS number
- 53164-05-9
- InChI Key
- FSQKKOOTNAMONP-UHFFFAOYSA-N
- InChI
- 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)
- IUPAC Name
- 2-({2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetyl}oxy)acetic acid
- SMILES
- COC1=CC2=C(C=C1)N(C(=O)C1=CC=C(Cl)C=C1)C(C)=C2CC(=O)OCC(O)=O
References
- General References
- Wada Y, Nakamura M, Kogo H, Aizawa Y: Inhibitory effect of acemetacin, a prodrug of indomethacin, on prostaglandin E2 release from inflamed synovial tissue. Jpn J Pharmacol. 1984 Apr;34(4):468-70. [Article]
- Jacobi H, Dell HD: [On the pharmacodynamics of acemetacin (author's transl)]. Arzneimittelforschung. 1980;30(8A):1348-62. [Article]
- Jones RW, Collins AJ, Notarianni LJ, Sedman E: The comparative pharmacokinetics of acemetacin in young subjects and elderly patients. Br J Clin Pharmacol. 1991 May;31(5):543-5. [Article]
- Dell HD, Doersing M, Fischer W, Jacobi H, Kamp R, Kohler G, Schollnhammer G: [Metabolism and pharmacokinetics of acemetacin in man (author's transl)]. Arzneimittelforschung. 1980;30(8A):1391-8. [Article]
- Ochs HR, Schuppan U, Greenblatt DJ, Abernethy DR: Reduced distribution and clearance of acetaminophen in patients with congestive heart failure. J Cardiovasc Pharmacol. 1983 Jul-Aug;5(4):697-9. [Article]
- Acton A. (2011). Issues in Pharmacology, Pharmacy, Drug Research and Drug Innovation . ScholarlyEditions.
- Sneader W. (2005). Drug discovery a history. Wiley.
- Chian R., Nargund G. and Huang J. (2017). Development of In vitro maturation for human oocytes. Springer.
- Seyffart G. (1992). Drug dosage in renal insufficiency (2nd ed.). Springer Science+Business Media Dordrecht.
- Rantudil label [Link]
- Emflex label [Link]
- Vademecum [Link]
- DIMDI Product Information: acemetacin oral capsule [Link]
- External Links
- KEGG Drug
- D01582
- PubChem Compound
- 1981
- PubChem Substance
- 347829316
- ChemSpider
- 1904
- BindingDB
- 50336272
- 16695
- ChEBI
- 31162
- ChEMBL
- CHEMBL189171
- ZINC
- ZINC000000601272
- PharmGKB
- PA166049184
- Wikipedia
- Acemetacin
- MSDS
- Download (32.4 KB)
Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral 30 MG Capsule Oral 60 MG Capsule, extended release Oral 90 mg Capsule Oral 90.000 mg Capsule, coated Oral 60 mg Capsule Oral 90 mg Capsule Oral 60.000 mg Capsule Oral Capsule, delayed release Oral Capsule Oral 90.00 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 151.5ºC 'MSDS' boiling point (°C) 637ºC 'MSDS' water solubility Slightly soluble 'MSDS' logP 4.49 Lead Optimization for Medicinal Chemists. Zaragoza Dorwald F. (2012). Wiley-VCH pKa 2.6 'MSDS' - Predicted Properties
Property Value Source Water Solubility 0.00229 mg/mL ALOGPS logP 3.71 ALOGPS logP 3.15 Chemaxon logS -5.3 ALOGPS pKa (Strongest Acidic) 3.26 Chemaxon pKa (Strongest Basic) -2.3 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 94.83 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 105.66 m3·mol-1 Chemaxon Polarizability 41.23 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 190.35493 predictedDeepCCS 1.0 (2019) [M+H]+ 192.71294 predictedDeepCCS 1.0 (2019) [M+Na]+ 199.08537 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Prostaglandin-endoperoxide synthase activity
- Specific Function
- Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
- Gene Name
- PTGS1
- Uniprot ID
- P23219
- Uniprot Name
- Prostaglandin G/H synthase 1
- Molecular Weight
- 68685.82 Da
References
- Sneader W. (2005). Drug discovery a history. Wiley.
- Chian R., Nargund G. and Huang J. (2017). Development of In vitro maturation for human oocytes. Springer.
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Prostaglandin-endoperoxide synthase activity
- Specific Function
- Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
- Gene Name
- PTGS2
- Uniprot ID
- P35354
- Uniprot Name
- Prostaglandin G/H synthase 2
- Molecular Weight
- 68995.625 Da
References
- Sneader W. (2005). Drug discovery a history. Wiley.
- Chian R., Nargund G. and Huang J. (2017). Development of In vitro maturation for human oocytes. Springer.
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Glucuronosyltransferase activity
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.Its unique specificity for 3,4-catechol estrogens and estriol su...
- Gene Name
- UGT2B7
- Uniprot ID
- P16662
- Uniprot Name
- UDP-glucuronosyltransferase 2B7
- Molecular Weight
- 60694.12 Da
References
- Seyffart G. (1992). Drug dosage in renal insufficiency (2nd ed.). Springer Science+Business Media Dordrecht.
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Transporter activity
- Specific Function
- Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotre...
- Gene Name
- ABCC1
- Uniprot ID
- P33527
- Uniprot Name
- Multidrug resistance-associated protein 1
- Molecular Weight
- 171589.5 Da
References
- Dittmar T. and Zanker K. (2009). Stem cell biology in health and disease. Springer.
Drug created at June 23, 2017 20:48 / Updated at May 22, 2021 06:01