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

Molecular Formula	C17H20NO3
Molecular Weight	286.3456
Charge	-1
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Molecular Formula	Na
Molecular Weight	22.9898
Charge	1
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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 76 Target ID: GO:0070527 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12511226	Inhibitor 8297	15.0 µM [IC50]
Cyclooxygenase-1 127 Target ID: CHEMBL221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9650852	Inhibitor 8297	122.0 µM [IC50]
Cyclooxygenase-2 196 Target ID: CHEMBL230 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18752957	Inhibitor 8297	2.0 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Osteoarthritis 157 Sources: https://www.drugs.com/pro/etodolac.html	Primary	Approved 8429	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 316 Sources: https://www.drugs.com/pro/etodolac.html	Primary	Approved 8429	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 8429	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

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

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

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) n = 493 Health Status: unhealthy Condition: osteoarthritis Age Group: 55.2 (31-64) Sex: M+F Population Size: 493 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 Page: 0654D-357-US, -358-US, -370-US, and -371-US.	unhealthy, 55.2 (31-64) n = 493 Health Status: unhealthy Condition: osteoarthritis Age Group: 55.2 (31-64) Sex: M+F Population Size: 493 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20-584S003_Lodine_medr.pdf Page: 0654D-357-US, -358-US, -370-US, and -371-US.	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 Page: 0654D-357-US, -358-US, -370-US, and -371-US.

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) n = 493 Health Status: unhealthy Condition: osteoarthritis Age Group: 55.2 (31-64) Sex: M+F Population Size: 493 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) n = 493 Health Status: unhealthy Condition: osteoarthritis Age Group: 55.2 (31-64) Sex: M+F Population Size: 493 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) n = 493 Health Status: unhealthy Condition: osteoarthritis Age Group: 55.2 (31-64) Sex: M+F Population Size: 493 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 Page: 0654D-357-US, -358-US, -370-US, and -371-US.	unhealthy, 55.2 (31-64) n = 493 Health Status: unhealthy Condition: osteoarthritis Age Group: 55.2 (31-64) Sex: M+F Population Size: 493 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20-584S003_Lodine_medr.pdf Page: 0654D-357-US, -358-US, -370-US, and -371-US.

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	substrate 1037 inhibitor 1767	substrate 1217 inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2A6 707 CYP2C19 1478 CYP2E1 882 PEPT1 20 OAT1 599	UGT1A10 291 UGT2B7 389 UGT2B15 203 CYP1A2 1054 CYP2A6 543 CYP2B6 664 CYP2C8 693 CYP2C19 991 CYP2E1 667 UGT1A1 418 UGT1A3 422 UGT1A4 347 UGT1A6 307 UGT1A7 236 UGT1A8 283 UGT1A9 380

Drug as perpetrator

Target	Modality	Activity
CYP2A6 739	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16430028/	no
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16430028/	no
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16430028/	no
CYP2E1 970	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16430028/	no
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16430028/	no
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16430028/	weak [IC50 122 uM]
OAT1 603	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22841915/	weak [IC50 50 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16430028/	yes [Ki 64 uM]
PEPT1 22	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20726987/	yes

Drug as victim

Target	Modality	Activity
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	major
UGT1A9 380	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	major
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	minor
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	minor
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	minor
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	minor
UGT1A1 418	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	no
UGT1A4 347	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	no
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	weak
CYP2A6 543	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	weak
CYP2B6 664	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	weak
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	weak
UGT1A10 291	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	yes
UGT1A3 422	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	yes
UGT1A6 307	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	yes
UGT1A7 236	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	yes
UGT1A8 283	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	yes
UGT2B15 203	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	yes
UGT2B7 389	substrate 3367 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
MolPort	MolPort-001-759-084	https://www.molport.com/shop/molecule-link/MolPort-001-759-084
eMolecules	537847	https://www.emolecules.com/cgi-bin/more?vid=537847

PubMed

Title	Date	PubMed
Efficacy and tolerability of etodolac in aged patients affected by degenerative joint disease (osteoarthritis) in its active phase.	1994	7927957
Fulminant hepatic failure associated with etodolac use.	1995 Apr	7717333
Nonsteroidal antiinflammatory drug induced hypersensitivity vasculitis clinically mimicking temporal arteritis.	1996 Jan	8838531
Biochemical and pharmacological profile of a tetrasubstituted furanone as a highly selective COX-2 inhibitor.	1997 May	9146894
Sulindac and a cyclooxygenase-2 inhibitor, etodolac, increase APC mRNA in the colon of rats treated with azoxymethane.	2000 Dec	11076880
Selective cyclooxygenase-2 inhibitors show a differential ability to inhibit proliferation and induce apoptosis of colon adenocarcinoma cells.	2002 Nov 6	12417326
Determination of expression of cyclooxygenase-1 and -2 isozymes in canine tissues and their differential sensitivity to nonsteroidal anti-inflammatory drugs.	2004 Jun	15198222
Etodolac inhibits EBER expression and induces Bcl-2-regulated apoptosis in Burkitt's lymphoma cells.	2005 Sep	16104877
Combination of cyclooxygenase-2 inhibitors and oxaliplatin increases the growth inhibition and death in human colon cancer cells.	2005 Sep 1	16004971
Etodolac induces apoptosis and inhibits cell adhesion to bone marrow stromal cells in human myeloma cells.	2006 Feb	16046235
One center's experience: the serology and drugs associated with drug-induced immune hemolytic anemia--a new paradigm.	2007 Apr	17381629
In vitro inhibition of CYP1A2 by model inhibitors, anti-inflammatory analgesics and female sex steroids: predictability of in vivo interactions.	2008 Aug	18816299
Dextran-etodolac conjugates: synthesis, in vitro and in vivo evaluation.	2009 Mar-Apr	19719056
Blurred vision and weakness in a 60-year-old woman.	2010 May	20466255
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.	2015 May 18	25811541

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)

Substance Class	Chemical Created by `admin` on `Sat Dec 16 01:54:21 GMT 2023` Edited by `admin` on `Sat Dec 16 01:54:21 GMT 2023`
Record UNII	VIQ282YI0V
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

ETODOLAC SODIUM

Common Name

English

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

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