U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula C17H21NO3
Molecular Weight 287.3542
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ETODOLAC

SMILES

CCc1cccc2c3CCOC(CC)(CC(=O)O)c3[nH]c12

InChI

InChIKey=NNYBQONXHNTVIJ-UHFFFAOYSA-N
InChI=1S/C17H21NO3/c1-3-11-6-5-7-12-13-8-9-21-17(4-2,10-14(19)20)16(13)18-15(11)12/h5-7,18H,3-4,8-10H2,1-2H3,(H,19,20)

HIDE SMILES / InChI

Description
Curator's Comment:: https://www.drugs.com/pro/etodolac.html

Etodolac is an anti-inflammatory agent with analgesic and antipyretic properties. It is used to treat osteoarthritis, rheumatoid arthritis and control acute pain. The therapeutic effects of etodolac are achieved via inhibition of the synthesis of prostaglandins involved in fever, pain, swelling and inflammation. Etodolac is administered as a racemate. As with other NSAIDs, the S-form has been shown to be active while the R-form is inactive. Both enantiomers are stable and there is no evidence of R- to S- conversion in vivo. Similar to other NSAIDs, the anti-inflammatory effects of etodolac result from inhibition of the enzyme cycooxygenase (COX). This decreases the synthesis of peripheral prostaglandins involved in mediating inflammation. Etodolac binds to the upper portion of the COX enzyme active site and prevents its substrate, arachidonic acid, from entering the active site. Etodolac was previously thought to be a non-selective COX inhibitor, but it is now known to be 5 – 50 times more selective for COX-2 than COX-1. Antipyresis may occur by central action on the hypothalamus, resulting in peripheral dilation, increased cutaneous blood flow, and subsequent heat loss. Etodolac is used for acute and long-term management of signs and symptoms of osteoarthritis and rheumatoid arthritis, as well as for the management of pain. Lodine, the brand-name formulation of the drug, has been discontinued in the United States, and only the generic form of etodolac is available.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
15 µM [IC50]
122 µM [IC50]
2 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Etodolac

Approved Use

Etodolac Capsules and Tablets, USP are indicated: For acute and long-term use in the management of signs and symptoms of the following: Osteoarthritis Rheumatoid arthritis For the management of acute pain

Launch Date

880416000000
Primary
Etodolac

Approved Use

Etodolac Capsules and Tablets, USP are indicated: For acute and long-term use in the management of signs and symptoms of the following: Osteoarthritis Rheumatoid arthritis For the management of acute pain

Launch Date

880416000000
Palliative
Etodolac

Approved Use

Etodolac Capsules and Tablets, USP are indicated: For acute and long-term use in the management of signs and symptoms of the following: Osteoarthritis Rheumatoid arthritis For the management of acute pain

Launch Date

880416000000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
15.9 μg/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ETODOLAC serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
17.8 μg/mL
200 mg 2 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ETODOLAC serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
14.5 μg/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ETODOLAC serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
65.8 μg × h/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ETODOLAC serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
81 μg × h/mL
200 mg 2 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ETODOLAC serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
84 μg × h/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ETODOLAC serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
6 h
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ETODOLAC serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
6.5 h
200 mg 2 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ETODOLAC serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
6.1 h
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ETODOLAC serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
1200 mg 1 times / day multiple, oral
Highest studied dose
dose: 1200 mg 1 times / day
route: oral
experiment_type: multiple
dose_type: Highest studied dose
co-adm with
    data_source:
    https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20-584S003_Lodine_medr.pdf
    unhealthy, 55.2 (31-64)
    population: unhealthy
    age: 55.2 (31-64)
    sex: M+F
    food_status:
    n:
    data_source:
    https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20-584S003_Lodine_medr.pdf
    Disc. AE: Abdominal pain, Diarrhea...
    AEs leading to
    discontinuation/dose reduction:​
    Abdominal pain (2%)
    Diarrhea (2%)
    Flatulence (1%)

    data_source:
    https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20-584S003_Lodine_medr.pdf
    1200 mg 1 times / day multiple, oral
    Highest studied dose
    dose: 1200 mg 1 times / day
    route: oral
    experiment_type: multiple
    dose_type: Highest studied dose
    co-adm with
      data_source:
      https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20-584S003_Lodine_medr.pdf
      unhealthy, 55.2 (31-64)
      population: unhealthy
      age: 55.2 (31-64)
      sex: M+F
      food_status:
      n:
      data_source:
      https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20-584S003_Lodine_medr.pdf
      Disc. AE: Insomnia...
      AEs leading to
      discontinuation/dose reduction:​
      Insomnia (<1)

      data_source:
      https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20-584S003_Lodine_medr.pdf
      AEs

      AEs

      AESignificanceDosePopulation
      Flatulence 1%
      Disc. AE
      1200 mg 1 times / day multiple, oral
      Highest studied dose
      dose: 1200 mg 1 times / day
      route: oral
      experiment_type: multiple
      dose_type: Highest studied dose
      co-adm with
        data_source:
        https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20-584S003_Lodine_medr.pdf
        unhealthy, 55.2 (31-64)
        Abdominal pain 2%
        Disc. AE
        1200 mg 1 times / day multiple, oral
        Highest studied dose
        dose: 1200 mg 1 times / day
        route: oral
        experiment_type: multiple
        dose_type: Highest studied dose
        co-adm with
          data_source:
          https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20-584S003_Lodine_medr.pdf
          unhealthy, 55.2 (31-64)
          Diarrhea 2%
          Disc. AE
          1200 mg 1 times / day multiple, oral
          Highest studied dose
          dose: 1200 mg 1 times / day
          route: oral
          experiment_type: multiple
          dose_type: Highest studied dose
          co-adm with
            data_source:
            https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20-584S003_Lodine_medr.pdf
            unhealthy, 55.2 (31-64)
            Insomnia <1%
            Disc. AE
            1200 mg 1 times / day multiple, oral
            Highest studied dose
            dose: 1200 mg 1 times / day
            route: oral
            experiment_type: multiple
            dose_type: Highest studied dose
            co-adm with
              data_source:
              https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20-584S003_Lodine_medr.pdf
              unhealthy, 55.2 (31-64)
              OverviewDrug as perpetrator​Drug as victim

              Drug as victim

              TargetModalityActivityMetaboliteClinical evidence
              major
              major
              minor
              minor
              minor
              minor
              no
              no
              weak
              weak
              weak
              weak
              yes
              yes
              yes
              yes
              yes
              yes
              yes
              PubMed

              PubMed

              TitleDatePubMed
              [Allergic vasculitis caused by etodolac. The first case].
              1989
              Efficacy and tolerability of etodolac in aged patients affected by degenerative joint disease (osteoarthritis) in its active phase.
              1994
              Anti-inflammatory effects of etodolac: comparison with other non-steroidal anti-inflammatory drugs.
              1994 Dec
              Fulminant hepatic failure associated with etodolac use.
              1995 Apr
              Nonsteroidal antiinflammatory drug induced hypersensitivity vasculitis clinically mimicking temporal arteritis.
              1996 Jan
              Biochemical and pharmacological profile of a tetrasubstituted furanone as a highly selective COX-2 inhibitor.
              1997 May
              Reactive oxygen species are involved in the apoptosis induced by nonsteroidal anti-inflammatory drugs in cultured gastric cells.
              1999 Nov 3
              The effect of NSAIDs and a COX-2 specific inhibitor on Helicobacter pylori-induced PGE2 and HGF in human gastric fibroblasts.
              2000 Apr
              Sulindac and a cyclooxygenase-2 inhibitor, etodolac, increase APC mRNA in the colon of rats treated with azoxymethane.
              2000 Dec
              Immune hemolytic anemia caused by sensitivity to a metabolite of etodolac, a nonsteroidal anti-inflammatory drug.
              2000 Jun
              Cyclooxygenase-1 and cyclooxygenase-2 selectivity of non-steroidal anti-inflammatory drugs: investigation using human peripheral monocytes.
              2001 Dec
              Selective cyclooxygenase-2 inhibitors show a differential ability to inhibit proliferation and induce apoptosis of colon adenocarcinoma cells.
              2002 Nov 6
              Search of antimicrobial activity of selected non-antibiotic drugs.
              2002 Nov-Dec
              Determination of expression of cyclooxygenase-1 and -2 isozymes in canine tissues and their differential sensitivity to nonsteroidal anti-inflammatory drugs.
              2004 Jun
              Carboxyl nonsteroidal anti-inflammatory drugs are efficiently glucuronidated by microsomes of the human gastrointestinal tract.
              2004 Nov 18
              The R-enantiomer of the nonsteroidal antiinflammatory drug etodolac binds retinoid X receptor and induces tumor-selective apoptosis.
              2005 Feb 15
              Etodolac inhibits EBER expression and induces Bcl-2-regulated apoptosis in Burkitt's lymphoma cells.
              2005 Sep
              Combination of cyclooxygenase-2 inhibitors and oxaliplatin increases the growth inhibition and death in human colon cancer cells.
              2005 Sep 1
              Ocular adverse effects associated with cyclooxygenase-2 inhibitors.
              2006 Feb
              Etodolac, a selective cyclooxygenase-2 inhibitor, inhibits liver metastasis of colorectal cancer cells via the suppression of MMP-9 activity.
              2006 Feb
              Etodolac induces apoptosis and inhibits cell adhesion to bone marrow stromal cells in human myeloma cells.
              2006 Feb
              Involvement of cyclooxygenase-2 in allergic nasal inflammation in rats.
              2006 Nov
              Membranous nephropathy associated with the relatively selective cyclooxygenase-2 inhibitor, etodolac, in a patient with early rheumatoid arthritis.
              2007
              One center's experience: the serology and drugs associated with drug-induced immune hemolytic anemia--a new paradigm.
              2007 Apr
              Safety of selective cyclooxygenase-2 inhibitors and a basic non-steroidal anti-inflammatory drug (NSAID) in Japanese patients with NSAID-induced urticaria and/or angioedema: Comparison of meloxicam, etodolac and tiaramide.
              2007 Mar
              Spectrophotometric determination of etodolac in pure form and pharmaceutical formulations.
              2008 Apr 14
              In vitro inhibition of CYP1A2 by model inhibitors, anti-inflammatory analgesics and female sex steroids: predictability of in vivo interactions.
              2008 Aug
              Dextran-etodolac conjugates: synthesis, in vitro and in vivo evaluation.
              2009 Mar-Apr
              Blurred vision and weakness in a 60-year-old woman.
              2010 May
              Sacroiliitis and severe disability due to isotretinoin therapy.
              2010 May
              Assessing the cardiovascular risk between celecoxib and nonselective nonsteroidal antiinflammatory drugs in patients with rheumatoid arthritis and osteoarthritis.
              2014
              Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.
              2015 May 18
              Patents

              Sample Use Guides

              In Vivo Use Guide
              Usual Adult Dose for Osteoarthritis or Rheumatoid Arthritis
              Route of Administration: Oral
              Etodolac significantly reduced cell viability of FMS-1 cells in a dosedependent
              Name Type Language
              ETODOLAC
              EP   GREEN BOOK   INN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
              USAN   INN  
              Official Name English
              ETODOLAC [USP MONOGRAPH]
              Common Name English
              NAPILAC
              Brand Name English
              (+/-)-1,8-DIETHYL-1,3,4,9-TETRAHYDROPYRANO(3,4-B)INDOLE-1-ACETIC ACID
              Systematic Name English
              EDOLAN
              Brand Name English
              ETODOLAC [USAN]
              Common Name English
              ETODOLAC [USP-RS]
              Common Name English
              ZEDOLAC
              Brand Name English
              AY-24,236
              Code English
              TEDOLAN
              Brand Name English
              LODIN XL
              Brand Name English
              AY-24236
              Code English
              ETODOLIC ACID
              Common Name English
              ETODOLAC [MI]
              Common Name English
              PYRANO(3,4-B)INDOLE-1-ACETIC ACID, 1,8-DIETHYL-1,3,4,9-TETRAHYDRO-(+/-)-
              Common Name English
              1,8-DIETHYL-1,3,4,9-TETRAHYDROPYRANO(3,4-B)INDOL-1-ACETIC ACID
              Systematic Name English
              ETODOLAC [INN]
              Common Name English
              (+/-)-ETODOLAC
              Common Name English
              ETODOLAC [VANDF]
              Common Name English
              FLANCOX
              Brand Name English
              PYRANO(3,4-B)INDOLE-1-ACETIC ACID, 1,8-DIETHYL-1,3,4,9-TETRAHYDRO-
              Systematic Name English
              1,8-DIETHYL-1,3,4,9-TETRAHYDROPYRANO(3,4-B)INDOLE-1-ACETIC ACID
              Systematic Name English
              RAMODAR
              Brand Name English
              LODINE
              Brand Name English
              ETODOLAC [MART.]
              Common Name English
              (RS)-ETODOLIC ACID
              Common Name English
              NIH-9918
              Code English
              NSC-282126
              Code English
              ETODOLAC [EP MONOGRAPH]
              Common Name English
              ULTRADOL
              Brand Name English
              ETODOLAC [GREEN BOOK]
              Common Name English
              ECCOXOLAC
              Brand Name English
              AY-24-236
              Code English
              ETODOLAC [WHO-DD]
              Common Name English
              ETODOLAC [ORANGE BOOK]
              Common Name English
              Classification Tree Code System Code
              NCI_THESAURUS C257
              Created by admin on Fri Jun 25 20:56:09 UTC 2021 , Edited by admin on Fri Jun 25 20:56:09 UTC 2021
              FDA ORPHAN DRUG 454614
              Created by admin on Fri Jun 25 20:56:09 UTC 2021 , Edited by admin on Fri Jun 25 20:56:09 UTC 2021
              WHO-VATC QM01AB08
              Created by admin on Fri Jun 25 20:56:09 UTC 2021 , Edited by admin on Fri Jun 25 20:56:09 UTC 2021
              FDA ORPHAN DRUG 475715
              Created by admin on Fri Jun 25 20:56:09 UTC 2021 , Edited by admin on Fri Jun 25 20:56:09 UTC 2021
              NDF-RT N0000175722
              Created by admin on Fri Jun 25 20:56:09 UTC 2021 , Edited by admin on Fri Jun 25 20:56:09 UTC 2021
              CFR 21 CFR 520.870
              Created by admin on Fri Jun 25 20:56:09 UTC 2021 , Edited by admin on Fri Jun 25 20:56:09 UTC 2021
              LIVERTOX 387
              Created by admin on Fri Jun 25 20:56:09 UTC 2021 , Edited by admin on Fri Jun 25 20:56:09 UTC 2021
              CFR 21 CFR 522.870
              Created by admin on Fri Jun 25 20:56:09 UTC 2021 , Edited by admin on Fri Jun 25 20:56:09 UTC 2021
              FDA ORPHAN DRUG 484315
              Created by admin on Fri Jun 25 20:56:09 UTC 2021 , Edited by admin on Fri Jun 25 20:56:09 UTC 2021
              WHO-ATC M01AB08
              Created by admin on Fri Jun 25 20:56:09 UTC 2021 , Edited by admin on Fri Jun 25 20:56:09 UTC 2021
              NDF-RT N0000000160
              Created by admin on Fri Jun 25 20:56:09 UTC 2021 , Edited by admin on Fri Jun 25 20:56:09 UTC 2021
              NDF-RT N0000175721
              Created by admin on Fri Jun 25 20:56:09 UTC 2021 , Edited by admin on Fri Jun 25 20:56:09 UTC 2021
              Code System Code Type Description
              PUBCHEM
              3308
              Created by admin on Fri Jun 25 20:56:09 UTC 2021 , Edited by admin on Fri Jun 25 20:56:09 UTC 2021
              PRIMARY
              WIKIPEDIA
              ETODOLAC
              Created by admin on Fri Jun 25 20:56:09 UTC 2021 , Edited by admin on Fri Jun 25 20:56:09 UTC 2021
              PRIMARY
              RXCUI
              24605
              Created by admin on Fri Jun 25 20:56:09 UTC 2021 , Edited by admin on Fri Jun 25 20:56:09 UTC 2021
              PRIMARY RxNorm
              DRUG BANK
              DB00749
              Created by admin on Fri Jun 25 20:56:09 UTC 2021 , Edited by admin on Fri Jun 25 20:56:09 UTC 2021
              PRIMARY
              NCI_THESAURUS
              C47526
              Created by admin on Fri Jun 25 20:56:09 UTC 2021 , Edited by admin on Fri Jun 25 20:56:09 UTC 2021
              PRIMARY
              LACTMED
              Etodolac
              Created by admin on Fri Jun 25 20:56:09 UTC 2021 , Edited by admin on Fri Jun 25 20:56:09 UTC 2021
              PRIMARY
              EVMPD
              SUB07316MIG
              Created by admin on Fri Jun 25 20:56:09 UTC 2021 , Edited by admin on Fri Jun 25 20:56:09 UTC 2021
              PRIMARY
              IUPHAR
              7185
              Created by admin on Fri Jun 25 20:56:09 UTC 2021 , Edited by admin on Fri Jun 25 20:56:09 UTC 2021
              PRIMARY
              DRUG CENTRAL
              1103
              Created by admin on Fri Jun 25 20:56:09 UTC 2021 , Edited by admin on Fri Jun 25 20:56:09 UTC 2021
              PRIMARY
              INN
              3715
              Created by admin on Fri Jun 25 20:56:09 UTC 2021 , Edited by admin on Fri Jun 25 20:56:09 UTC 2021
              PRIMARY
              CAS
              41340-25-4
              Created by admin on Fri Jun 25 20:56:09 UTC 2021 , Edited by admin on Fri Jun 25 20:56:09 UTC 2021
              PRIMARY
              MESH
              D017308
              Created by admin on Fri Jun 25 20:56:09 UTC 2021 , Edited by admin on Fri Jun 25 20:56:09 UTC 2021
              PRIMARY
              FDA UNII
              2M36281008
              Created by admin on Fri Jun 25 20:56:09 UTC 2021 , Edited by admin on Fri Jun 25 20:56:09 UTC 2021
              PRIMARY
              ChEMBL
              CHEMBL622
              Created by admin on Fri Jun 25 20:56:09 UTC 2021 , Edited by admin on Fri Jun 25 20:56:09 UTC 2021
              PRIMARY
              MERCK INDEX
              M5190
              Created by admin on Fri Jun 25 20:56:09 UTC 2021 , Edited by admin on Fri Jun 25 20:56:09 UTC 2021
              PRIMARY Merck Index
              USP_CATALOG
              1268706
              Created by admin on Fri Jun 25 20:56:09 UTC 2021 , Edited by admin on Fri Jun 25 20:56:09 UTC 2021
              PRIMARY USP-RS
              CAS
              87226-38-8
              Created by admin on Fri Jun 25 20:56:09 UTC 2021 , Edited by admin on Fri Jun 25 20:56:09 UTC 2021
              SUPERSEDED
              EPA CompTox
              41340-25-4
              Created by admin on Fri Jun 25 20:56:09 UTC 2021 , Edited by admin on Fri Jun 25 20:56:09 UTC 2021
              PRIMARY