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	Na
Molecular Weight	22.9898
Charge	1
Count

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

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	( + / - )

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 75 Target ID: GO:0070527 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12511226	Inhibitor 8146	15.0 µM [IC50]
Cyclooxygenase-1 125 Target ID: CHEMBL221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9650852	Inhibitor 8146	122.0 µM [IC50]
Cyclooxygenase-2 191 Target ID: CHEMBL230 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18752957	Inhibitor 8146	2.0 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Osteoarthritis 155 Sources: https://www.drugs.com/pro/etodolac.html	Primary	Approved 8307	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 8.80416E11
Rheumatoid arthritis 310 Sources: https://www.drugs.com/pro/etodolac.html	Primary	Approved 8307	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 8.80416E11
Acute pain 17 Sources: https://www.drugs.com/pro/etodolac.html	Palliative	Approved 8307	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 8.80416E11

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 1670 inhibitor 1532	substrate 985 inhibitor 1695	substrate 1168 inhibitor 1789

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1463 CYP2A6 670 CYP2C19 1410 CYP2E1 846 PEPT1 20 OAT1 584	UGT1A10 289 UGT2B7 387 UGT2B15 202 CYP1A2 1013 CYP2A6 510 CYP2B6 648 CYP2C8 670 CYP2C19 955 CYP2E1 633 UGT1A1 417 UGT1A3 421 UGT1A4 345 UGT1A6 306 UGT1A7 235 UGT1A8 282 UGT1A9 378

Drug as perpetrator

Target	Modality	Activity
CYP2A6 702	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/16430028/	no
CYP2C19 1484	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/16430028/	no
CYP2D6 1826	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/16430028/	no
CYP2E1 929	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/16430028/	no
CYP3A4 1857	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/16430028/	no
CYP1A2 1620	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/16430028/	weak [IC50 122 uM]
OAT1 588	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/22841915/	weak [IC50 50 uM]
CYP2C9 1747	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/16430028/	yes [Ki 64 uM]
PEPT1 22	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/20726987/	yes

Drug as victim

Target	Modality	Activity
CYP2C9 985	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	major
UGT1A9 378	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	major
CYP2C19 955	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	minor
CYP2C8 670	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	minor
CYP2D6 1168	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	minor
CYP3A4 1670	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	minor
UGT1A1 417	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	no
UGT1A4 345	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	no
CYP1A2 1013	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	weak
CYP2A6 510	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	weak
CYP2B6 648	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	weak
CYP2E1 633	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	weak
UGT1A10 289	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	yes
UGT1A3 421	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	yes
UGT1A6 306	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	yes
UGT1A7 235	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	yes
UGT1A8 282	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	yes
UGT2B15 202	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/15370961/	yes
UGT2B7 387	substrate 3264 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
Fulminant hepatic failure associated with etodolac use.	1995 Apr	7717333
Reactive oxygen species are involved in the apoptosis induced by nonsteroidal anti-inflammatory drugs in cultured gastric cells.	1999 Nov 3	10594327
Immune hemolytic anemia caused by sensitivity to a metabolite of etodolac, a nonsteroidal anti-inflammatory drug.	2000 Jun	10864985
Cyclooxygenase-1 and cyclooxygenase-2 selectivity of non-steroidal anti-inflammatory drugs: investigation using human peripheral monocytes.	2001 Dec	11804398
Search of antimicrobial activity of selected non-antibiotic drugs.	2002 Nov-Dec	12669766
Etodolac inhibits EBER expression and induces Bcl-2-regulated apoptosis in Burkitt's lymphoma cells.	2005 Sep	16104877
Ocular adverse effects associated with cyclooxygenase-2 inhibitors.	2006 Feb	16476901
Etodolac, a selective cyclooxygenase-2 inhibitor, inhibits liver metastasis of colorectal cancer cells via the suppression of MMP-9 activity.	2006 Feb	16391837
Membranous nephropathy associated with the relatively selective cyclooxygenase-2 inhibitor, etodolac, in a patient with early rheumatoid arthritis.	2007	17603251
One center's experience: the serology and drugs associated with drug-induced immune hemolytic anemia--a new paradigm.	2007 Apr	17381629
Assessing the cardiovascular risk between celecoxib and nonselective nonsteroidal antiinflammatory drugs in patients with rheumatoid arthritis and osteoarthritis.	2014	24152722
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 17 13:08:45 UTC 2022` Edited by `admin` on `Sat Dec 17 13:08:45 UTC 2022`
Record UNII	VIQ282YI0V
Record Status	`Validated (UNII)`
Record Version

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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