Identification
- Generic Name
- Aceclofenac
- DrugBank Accession Number
- DB06736
- Background
Aceclofenac is an oral non-steroidal anti-inflammatory drug (NSAID) with marked anti-inflammatory and analgesic properties used to treat osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. It is reported to have a higher anti-inflammatory action or at least comparable effects than conventional NSAIDs in double-blind studies 2,3,5. Aceclofenac potently inhibits the cyclo-oxygenase enzyme (COX) that is involved in the synthesis of prostaglandins, which are inflammatory mediators that cause pain, swelling, inflammation, and fever. Aceclofenac belongs to BCS Class II as it possesses poor aqueous solubility 2. It displays high permeability to penetrate into synovial joints where in patients with osteoarthritis and related conditions, the loss of articular cartilage in the area causes joint pain, tenderness, stiffness, crepitus, and local inflammation 1. Aceclofenac is also reported to be effective in other painful conditions such as dental and gynaecological conditions 7. In 1991, aceclofenac was developed as an analog of a commonly prescribed NSAID, Diclofenac, via chemical modification in effort to improve the gastrointestinal tolerability of the drug. It is a more commonly prescribed drug in Europe.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Aceclofenac (DB06736)
- Weight
- Average: 354.18
Monoisotopic: 353.0221633 - Chemical Formula
- C16H13Cl2NO4
- Synonyms
- 2-[(2,6-dichlorophenyl)amino]benzeneacetic acid carboxymethyl ester
- 2-[(2,6-dichlorophenyl)amino]phenylacetoxyacetic acid
- 2-[(2',6'-dichlorophenyl)amino]phenylacetoxyacetic acid
- Aceclofenac
- Acéclofénac
- Aceclofenac betadex
- Aceclofenaco
- Aceclofenacum
- glycolic acid [o-(2,6-dichloroanilino)phenyl]acetate ester
Pharmacology
- Indication
Aceclofenac is indicated for the relief of pain and inflammation in osteoarthritis, rheumatoid arthritis and ankylosing spondylitis.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Symptomatic treatment of Ankylosing spondylitis (as) •••••••••••• Symptomatic treatment of Osteoarthritis (oa) •••••••••••• Symptomatic treatment of Rheumatoid arthritis •••••••••••• - Contraindications & Blackbox Warnings
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Aceclofenac is a NSAID that inhibits both isoforms of COX enzyme, a key enzyme involved in the inflammatory cascade. COX-1 enzyme is a constitutive enzyme involved in prostacyclin production and protective functions of gastric mucosa whereas COX-2 is an inducible enzyme involved in the production of inflammatory mediators in response to inflammatory stimuli. Aceclofenac displays more selectivity towards COX-2 (IC50 of 0.77uM) than COX-1 (IC50 of >100uM), which promotes its gastric tolerance compared to other NSAIDs. The primary metabolite, 4'-hydroxyaceclofenac, also minimally inhibits COX-2 with IC50 value of 36uM 2. Although the mode of action of aceclofenac is thought to mainly arise from the inhibition of synthesis of prostaglandins (PGE2), aceclofenac also inhibits the production of inflammatory cytokines, interleukins (IL-1β, IL-6), and tumor necrosis factors (TNF) 1,2. It is also reported that aceclofenac also affects the cell adhesion molecules from neutrophils 8. Aceclofenac also targets the synthesis of glycosaminoglycan and mediates chrondroprotective effects 1.
- Mechanism of action
Through COX-2 inhibition, aceclofenac downregulates the production of various inflammatory mediators including prostaglandin E2 (PGE2), IL-1β, and TNF from the arachidonic acid (AA) pathway. Inhibition of IL-6 is thought to be mediated by diclofenac converted from aceclofenac 6. Suppressed action of inflammatory cytokines decreases the production of reactive oxygen species. Aceclofenac is shown to decreased production of nitrous oxide in human articular chondrocytes 2. In addition, aceclofenac interferes with neutrophil adhesion to endothelium by decreasing the expression of L-selectin (CD62L), which is a cell adhesion molecule expressed on lymphocytes 8. Aceclofenac is proposed to stimulate the synthesis of glycosaminoglycan in human osteoarthritic cartilage which may be mediated through its inhibitory action on IL-1 production and activity 1. The chrondroprotective effects are generated by 4'-hydroxyaceclofenac which suppresses IL-1 mediated production of promatrix metalloproteinase-1 and metalloproteinase-3 and interferes with the release of proteoglycan from chrondrocytes 1,2,7.
Target Actions Organism AProstaglandin G/H synthase 2 inhibitorHumans AProstaglandin G/H synthase 1 inhibitorHumans - Absorption
Aceclofenac is rapidly and completely absorbed from the gastrointestinal tract and circulates mainly as unchanged drug following oral administration. Peak plasma concentrations are reached around 1.25 to 3 hours post-ingestion, and the drug penetrates into the synovial fluid where the concentration may reach up to 60% of that in the plasma 11. There is no accumulation in regular dosing, with similar maximum plasma concentration (Cmax) and time to reach peak plasma concentration (Tmax) after single and multiple doses 2.
- Volume of distribution
The volume of distribution is approximately 25 L 11.
- Protein binding
It is reported to be highly protein-bound (>99%) 11.
- Metabolism
4'-hydroxyaceclofenac is the main metabolite detected in plasma however other minor metabolites include diclofenac, 5-hydroxyaceclofenac, 5-hydroxydiclofenac, and 4'-hydroxydiclofenac 2. It is probable that the metabolism of aceclofenac is mediated by CYP2C9 9.
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- Route of elimination
The main route of elimination is via the urine where the elimination accounts for 70-80% of clearance of the drug 2. Approximately two thirds of the administered dose is excreted via the urine, mainly as glucuronidated and hydroxylated forms of aceclofenac 11. About 20% of the dose is excreted into feces 6.
- Half-life
The mean plasma elimination half-life is approximately 4 hours 11.
- Clearance
The mean clearance rate is approximately 5 L/h 9.
- Adverse Effects
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Some common adverse effects include gastro-intestinal disorders (dyspepsia, abdominal pain, nausea), rash, ruber, urticaria, symptoms of enuresis, headache, dizziness, and drowsiness 12. Oral LD50 value in rats is 130 mg/kg MSDS.
- 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 Aceclofenac 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 Aceclofenac is combined with Abciximab. Acebutolol Aceclofenac may decrease the antihypertensive activities of Acebutolol. Acemetacin 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 Aceclofenac is combined with Acenocoumarol. - Food Interactions
- Take with or without food.
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
- Cincofen / Clanza / Hifenac
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Clanza CR Tablet, film coated 200 mg/1 Oral United Douglas Pharm., Inc. 2011-05-12 Not applicable US 
Categories
- ATC Codes
- M01AB16 — Aceclofenac
- M01AB — Acetic acid derivatives and related substances
- M01A — ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS, NON-STEROIDS
- M01 — ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS
- M — MUSCULO-SKELETAL SYSTEM
- Drug Categories
- Acetic Acid Derivatives and Related Substances
- Acids, Carbocyclic
- Agents causing hyperkalemia
- Agents that produce hypertension
- Analgesics
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)
- Antiinflammatory and Antirheumatic Products
- Antiinflammatory and Antirheumatic Products, Non-Steroids
- Antiinflammatory Preparations, Non-Steroids for Topical Use
- Antirheumatic Agents
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 Substrates
- Drugs that are Mainly Renally Excreted
- Musculo-Skeletal System
- Nephrotoxic agents
- Peripheral Nervous System Agents
- Phenylacetates
- Selective Cyclooxygenase 2 Inhibitors (NSAIDs)
- Sensory System Agents
- Topical Products for Joint and Muscular Pain
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as dichlorobenzenes. These are compounds containing a benzene with exactly two chlorine atoms attached to it.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Halobenzenes
- Direct Parent
- Dichlorobenzenes
- Alternative Parents
- Aniline and substituted anilines / Dicarboxylic acids and derivatives / Aryl chlorides / Carboxylic acid esters / Amino acids / Secondary amines / Carboxylic acids / Organopnictogen compounds / Organochlorides / Organic oxides show 2 more
- Substituents
- 1,3-dichlorobenzene / Amine / Amino acid / Amino acid or derivatives / Aniline or substituted anilines / Aromatic homomonocyclic compound / Aryl chloride / Aryl halide / Carbonyl group / Carboxylic acid show 13 more
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- monocarboxylic acid, carboxylic ester, secondary amino compound, dichlorobenzene, amino acid (CHEBI:31159)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- RPK779R03H
- CAS number
- 89796-99-6
- InChI Key
- MNIPYSSQXLZQLJ-UHFFFAOYSA-N
- InChI
- InChI=1S/C16H13Cl2NO4/c17-11-5-3-6-12(18)16(11)19-13-7-2-1-4-10(13)8-15(22)23-9-14(20)21/h1-7,19H,8-9H2,(H,20,21)
- IUPAC Name
- 2-[(2-{2-[(2,6-dichlorophenyl)amino]phenyl}acetyl)oxy]acetic acid
- SMILES
- OC(=O)COC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl
References
- General References
- Raza K, Kumar M, Kumar P, Malik R, Sharma G, Kaur M, Katare OP: Topical delivery of aceclofenac: challenges and promises of novel drug delivery systems. Biomed Res Int. 2014;2014:406731. doi: 10.1155/2014/406731. Epub 2014 Jun 18. [Article]
- Legrand E: Aceclofenac in the management of inflammatory pain. Expert Opin Pharmacother. 2004 Jun;5(6):1347-57. [Article]
- Pareek A, Chandurkar N: Comparison of gastrointestinal safety and tolerability of aceclofenac with diclofenac: a multicenter, randomized, double-blind study in patients with knee osteoarthritis. Curr Med Res Opin. 2013 Jul;29(7):849-59. doi: 10.1185/03007995.2013.795139. Epub 2013 Apr 30. [Article]
- Moore RA, Derry S, McQuay HJ: Single dose oral aceclofenac for postoperative pain in adults. Cochrane Database Syst Rev. 2009 Jul 8;(3):CD007588. doi: 10.1002/14651858.CD007588.pub2. [Article]
- Pareek A, Chandurkar N, Gupta A, Sirsikar A, Dalal B, Jesalpura B, Mehrotra A, Mukherjee A: Efficacy and safety of aceclofenac-cr and aceclofenac in the treatment of knee osteoarthritis: a 6-week, comparative, randomized, multicentric, double-blind study. J Pain. 2011 May;12(5):546-53. doi: 10.1016/j.jpain.2010.10.013. Epub 2011 Feb 1. [Article]
- Brogden RN, Wiseman LR: Aceclofenac. A review of its pharmacodynamic properties and therapeutic potential in the treatment of rheumatic disorders and in pain management. Drugs. 1996 Jul;52(1):113-24. doi: 10.2165/00003495-199652010-00008. [Article]
- Dooley M, Spencer CM, Dunn CJ: Aceclofenac: a reappraisal of its use in the management of pain and rheumatic disease. Drugs. 2001;61(9):1351-78. [Article]
- Gonzalez-Alvaro I, Carmona L, Diaz-Gonzalez F, Gonzalez-Amaro R, Mollinedo F, Sanchez-Madrid F, Laffon A, Garcia-Vicuna R: Aceclofenac, a new nonsteroidal antiinflammatory drug, decreases the expression and function of some adhesion molecules on human neutrophils. J Rheumatol. 1996 Apr;23(4):723-9. [Article]
- Ghosh S, Barik BB: A Comparative Study of the Pharmacokinetics of Conventional and Sustained-release Tablet Formulations of Aceclofenac in Healthy Male Subjects Tropical Journal of Pharmaceutical Research. 2010 September 1;9(4):395-399. [Article]
- Dahiya S, Kaushik A, Pathak K: Improved Pharmacokinetics of Aceclofenac Immediate Release Tablets Incorporating its Inclusion Complex with Hydroxypropyl-beta-Cyclodextrin. Sci Pharm. 2015 Feb 2;83(3):501-10. doi: 10.3797/scipharm.1509-07. Print 2015 Jul-Sep. [Article]
- UK Medicines and Healthcare products Regulatory Agency: ACECLOFENAC 100MG TABLETS product information [Link]
- DailyMed Label: Clanza CR (Aceclofenac) Oral Tablets [Link]
- External Links
- KEGG Drug
- D01545
- PubChem Compound
- 71771
- PubChem Substance
- 347827785
- ChemSpider
- 64809
- BindingDB
- 50109016
- 16689
- ChEBI
- 31159
- ChEMBL
- CHEMBL93645
- ZINC
- ZINC000003805798
- PharmGKB
- PA166049185
- Wikipedia
- Aceclofenac
- MSDS
- Download (45.6 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Basic Science Rheumatoid Arthritis 1 4 Completed Prevention NSAID-associated Gastroduodenal Injury 1 4 Completed Treatment Osteoarthritis (OA) 1 4 Completed Treatment Osteoarthritis of the Knee 1 3 Completed Treatment Disorder of Urinary Stent 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 100 mg Tablet, film coated Oral 100 mg Injection, powder, lyophilized, for solution Parenteral 0.15 g Tablet, film coated Oral 0.1 g Tablet, film coated Oral 100 mg/1 Cream Topical 1.5 g Drug delivery system Oral 100.000 mg Tablet Oral 100.00 mg Tablet, film coated Oral 200 mg/1 Cream Cutaneous 1.5 g Cream Topical 1.5 % Cream Topical 1.5 G/100G Injection, powder, for solution Intramuscular 150 MG/4ML Powder, for suspension Oral 100 MG Suppository 200 MG Cream Cutaneous 1.500 g Tablet, film coated Oral Tablet, extended release Oral 200 mg Tablet, coated Oral 100 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 149-153 MSDS water solubility Insoluble Wikipedia logP 2.170 Dahiya S, Kaushik A, and Pathak K, 2015 - Predicted Properties
Property Value Source Water Solubility 0.00199 mg/mL ALOGPS logP 4.88 ALOGPS logP 3.88 Chemaxon logS -5.2 ALOGPS pKa (Strongest Acidic) 3.44 Chemaxon pKa (Strongest Basic) -2.1 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 75.63 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 86.32 m3·mol-1 Chemaxon Polarizability 32.76 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No 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]- 165.80246 predictedDeepCCS 1.0 (2019) [M+H]+ 168.16045 predictedDeepCCS 1.0 (2019) [M+Na]+ 174.25362 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- 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
- Legrand E: Aceclofenac in the management of inflammatory pain. Expert Opin Pharmacother. 2004 Jun;5(6):1347-57. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- 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
- Legrand E: Aceclofenac in the management of inflammatory pain. Expert Opin Pharmacother. 2004 Jun;5(6):1347-57. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
- Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
Drug created at August 31, 2010 20:49 / Updated at February 03, 2022 21:01