ETODOLAC SODIUM

Details

Stereochemistry	RACEMIC
Molecular Formula	C17H20NO3.Na
Molecular Weight	309.3354
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].CCC1=CC=CC2=C1NC3=C2CCOC3(CC)CC([O-])=O

InChI

InChIKey=OYVVSFKYBAVZJZ-UHFFFAOYSA-M

InChI=1S/C17H21NO3.Na/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);/q;+1/p-1

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00749
Curator's Comment: Description was created based on several sources, including 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

Primary Target	Pharmacology	Potency
platelet aggregation 80 Target ID: GO:0070527 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12511226	Inhibitor 8504	15.0 µM [IC50]
Cyclooxygenase-1 131 Target ID: CHEMBL221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9650852	Inhibitor 8504	122.0 µM [IC50]
Cyclooxygenase-2 201 Target ID: CHEMBL230 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18752957	Inhibitor 8504	2.0 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Osteoarthritis 157 Sources: https://www.drugs.com/pro/etodolac.html	Primary	Approved 8583	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 1997
Rheumatoid arthritis 320 Sources: https://www.drugs.com/pro/etodolac.html	Primary	Approved 8583	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 1997
Acute pain 17 Sources: https://www.drugs.com/pro/etodolac.html	Palliative	Approved 8583	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 1997

C_max

Value	Dose	Analyte	Population
15.9 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2525981/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2525981/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2938343/	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
14.2 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28875479/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	ETODOLAC, (R)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28875479/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	ETODOLAC, (S)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
65.8 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2525981/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2525981/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2938343/	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
90.4 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28875479/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	ETODOLAC, (R)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
7.53 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28875479/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	ETODOLAC, (S)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2525981/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2525981/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2938343/	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
7.68 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28875479/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	ETODOLAC, (R)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
4.89 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28875479/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	ETODOLAC, (S)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
1200 mg 1 times / day multiple, oral Highest studied dose Dose: 1200 mg, 1 times / day Route: oral Route: multiple Dose: 1200 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20-584S003_Lodine_medr.pdf	unhealthy, 55.2 (31-64) Health Status: unhealthy Age Group: 55.2 (31-64) Sex: M+F Sources: 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%) Sources: 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 Route: multiple Dose: 1200 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20-584S003_Lodine_medr.pdf	unhealthy, 55.2 (31-64) Health Status: unhealthy Age Group: 55.2 (31-64) Sex: M+F Sources: 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%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20-584S003_Lodine_medr.pdf

AEs

AE	Significance	Dose	Population
Flatulence	1% Disc. AE	1200 mg 1 times / day multiple, oral Highest studied dose Dose: 1200 mg, 1 times / day Route: oral Route: multiple Dose: 1200 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20-584S003_Lodine_medr.pdf	unhealthy, 55.2 (31-64) Health Status: unhealthy Age Group: 55.2 (31-64) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20-584S003_Lodine_medr.pdf
Abdominal pain	2% Disc. AE	1200 mg 1 times / day multiple, oral Highest studied dose Dose: 1200 mg, 1 times / day Route: oral Route: multiple Dose: 1200 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20-584S003_Lodine_medr.pdf	unhealthy, 55.2 (31-64) Health Status: unhealthy Age Group: 55.2 (31-64) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20-584S003_Lodine_medr.pdf
Diarrhea	2% Disc. AE	1200 mg 1 times / day multiple, oral Highest studied dose Dose: 1200 mg, 1 times / day Route: oral Route: multiple Dose: 1200 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20-584S003_Lodine_medr.pdf	unhealthy, 55.2 (31-64) Health Status: unhealthy Age Group: 55.2 (31-64) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20-584S003_Lodine_medr.pdf
Insomnia	<1% Disc. AE	1200 mg 1 times / day multiple, oral Highest studied dose Dose: 1200 mg, 1 times / day Route: oral Route: multiple Dose: 1200 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20-584S003_Lodine_medr.pdf	unhealthy, 55.2 (31-64) Health Status: unhealthy Age Group: 55.2 (31-64) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20-584S003_Lodine_medr.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252	substrate 1193 inhibitor 2438	substrate 1388 inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2A6 879 CYP2C19 2057 CYP2E1 1060 PEPT1 27 OAT1 725	UGT1A10 331 UGT2B7 456 UGT2B15 236 CYP1A2 1197 CYP2A6 626 CYP2B6 776 CYP2C8 810 CYP2C19 1119 CYP2E1 729 UGT1A1 479 UGT1A3 470 UGT1A4 399 UGT1A6 343 UGT1A7 249 UGT1A8 323 UGT1A9 423

Drug as perpetrator

Target	Modality	Activity
CYP2A6 911	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/16430028/	no
CYP2C19 2141	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/16430028/	no
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/16430028/	no
CYP2E1 1146	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/16430028/	no
CYP3A4 2633	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/16430028/	no
CYP1A2 2333	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/16430028/	weak [IC50 122 uM]
OAT1 730	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22841915/	weak [IC50 50 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/16430028/	yes [Ki 64 uM]
PEPT1 29	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/20726987/	yes

Drug as victim

Target	Modality	Activity
CYP2C9 1193	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	major
UGT1A9 423	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	major
CYP2C19 1119	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	minor
CYP2C8 810	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	minor
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	minor
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	minor
UGT1A1 479	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	no
UGT1A4 399	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	no
CYP1A2 1197	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	weak
CYP2A6 626	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	weak
CYP2B6 776	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	weak
CYP2E1 729	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	weak
UGT1A10 331	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	yes
UGT1A3 470	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	yes
UGT1A6 343	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	yes
UGT1A7 249	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	yes
UGT1A8 323	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	yes
UGT2B15 236	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	yes
UGT2B7 456	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4909	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4909
eMolecules	537847	https://www.emolecules.com/cgi-bin/more?vid=537847
MolPort	MolPort-001-759-084	https://www.molport.com/shop/molecule-link/MolPort-001-759-084

PubMed

Title	Date	PubMed
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.	2015-05-18	25811541
Assessing the cardiovascular risk between celecoxib and nonselective nonsteroidal antiinflammatory drugs in patients with rheumatoid arthritis and osteoarthritis.	2014	24152722
Blurred vision and weakness in a 60-year-old woman.	2010-05	20466255
Sacroiliitis and severe disability due to isotretinoin therapy.	2010-05	19533139
Dextran-etodolac conjugates: synthesis, in vitro and in vivo evaluation.	2009-09-02	19719056
In vitro inhibition of CYP1A2 by model inhibitors, anti-inflammatory analgesics and female sex steroids: predictability of in vivo interactions.	2008-08	18816299
Spectrophotometric determination of etodolac in pure form and pharmaceutical formulations.	2008-04-14	18410679
One center's experience: the serology and drugs associated with drug-induced immune hemolytic anemia--a new paradigm.	2007-04	17381629
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.	2007-03	17291297
Membranous nephropathy associated with the relatively selective cyclooxygenase-2 inhibitor, etodolac, in a patient with early rheumatoid arthritis.	2007	17603251
Involvement of cyclooxygenase-2 in allergic nasal inflammation in rats.	2006-11	16979129
Ocular adverse effects associated with cyclooxygenase-2 inhibitors.	2006-02	16476901
Etodolac, a selective cyclooxygenase-2 inhibitor, inhibits liver metastasis of colorectal cancer cells via the suppression of MMP-9 activity.	2006-02	16391837
Etodolac induces apoptosis and inhibits cell adhesion to bone marrow stromal cells in human myeloma cells.	2006-02	16046235
Combination of cyclooxygenase-2 inhibitors and oxaliplatin increases the growth inhibition and death in human colon cancer cells.	2005-09-01	16004971
Etodolac inhibits EBER expression and induces Bcl-2-regulated apoptosis in Burkitt's lymphoma cells.	2005-09	16104877
The R-enantiomer of the nonsteroidal antiinflammatory drug etodolac binds retinoid X receptor and induces tumor-selective apoptosis.	2005-02-15	15699354
Carboxyl nonsteroidal anti-inflammatory drugs are efficiently glucuronidated by microsomes of the human gastrointestinal tract.	2004-11-18	15535975
Determination of expression of cyclooxygenase-1 and -2 isozymes in canine tissues and their differential sensitivity to nonsteroidal anti-inflammatory drugs.	2004-06	15198222
Search of antimicrobial activity of selected non-antibiotic drugs.	2003-04-03	12669766
Selective cyclooxygenase-2 inhibitors show a differential ability to inhibit proliferation and induce apoptosis of colon adenocarcinoma cells.	2002-11-06	12417326
Cyclooxygenase-1 and cyclooxygenase-2 selectivity of non-steroidal anti-inflammatory drugs: investigation using human peripheral monocytes.	2001-12	11804398
Sulindac and a cyclooxygenase-2 inhibitor, etodolac, increase APC mRNA in the colon of rats treated with azoxymethane.	2000-12	11076880
Immune hemolytic anemia caused by sensitivity to a metabolite of etodolac, a nonsteroidal anti-inflammatory drug.	2000-06	10864985
The effect of NSAIDs and a COX-2 specific inhibitor on Helicobacter pylori-induced PGE2 and HGF in human gastric fibroblasts.	2000-04	10807402
Reactive oxygen species are involved in the apoptosis induced by nonsteroidal anti-inflammatory drugs in cultured gastric cells.	1999-11-03	10594327
Biochemical and pharmacological profile of a tetrasubstituted furanone as a highly selective COX-2 inhibitor.	1997-05	9146894
Nonsteroidal antiinflammatory drug induced hypersensitivity vasculitis clinically mimicking temporal arteritis.	1996-01	8838531
Fulminant hepatic failure associated with etodolac use.	1995-04	7717333
Anti-inflammatory effects of etodolac: comparison with other non-steroidal anti-inflammatory drugs.	1994-12	7735198
Efficacy and tolerability of etodolac in aged patients affected by degenerative joint disease (osteoarthritis) in its active phase.	1994	7927957
[Allergic vasculitis caused by etodolac. The first case].	1989	2533855

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Osteoarthritis or Rheumatoid Arthritis Capsules or tablets: 300 mg orally 2 to 3 times a day or 400 mg orally twice a day or 500 mg orally twice a day. Total daily dose should not exceed 1200 mg.

Route of Administration: Oral

In Vitro Use Guide

Etodolac significantly reduced cell viability of FMS-1 cells in a dosedependent manner (0.125 mM - 1 mM)

Name

Type

Language

PYRANO(3,4-B)INDOLE-1-ACETIC ACID, 1,8-DIETHYL-1,3,4,9-TETRAHYDRO-, MONOSODIUM SALT

Preferred Name

English

ETODOLAC SODIUM

Common Name

English

SODIUM ETODOLATE

Common Name

English

PYRANO(3,4-B)INDOLE-1-ACETIC ACID, 1,8-DIETHYL-1,3,4,9-TETRAHYDRO-, SODIUM SALT (1:1)

Systematic Name

English

Code System Code Type Description

EPA CompTox

DTXSID50911859