Drug/Small Molecule:
etodolac

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This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Gene?
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • etodolac
Trade Names
  • Etodolac [Usan:Ban:Inn]
  • Etodolacetodolic acid
  • Etodolaco [INN-Spanish]
  • Etodolacum [INN-Latin]
  • Etodolic Acid
  • Lodine
  • Lodine XL
  • Ultradol
Brand Mixture Names

PharmGKB Accession Id:
PA449550

Description

Etodolac is a non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic and antipyretic properties. Its therapeutic effects are due to its ability to inhibit prostaglandin synthesis. It is indicated for relief of signs and symptoms of rheumatoid arthritis and osteoarthritis.

Source: Drug Bank

Indication

For acute and long-term management of signs and symptoms of osteoarthritis and rheumatoid arthritis, as well as for the management of pain.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

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.

Source: Drug Bank

Pharmacology

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.

Source: Drug Bank

Food Interaction

Avoid alcohol.|Food increases the peak plasma concentration of extended-release tablets with no effect on extent of absorption.|Take with food to reduce gastric irritation.|Food increases the time to peak concentration of regular release oral formulations by 1.4 to 3.8 hours with no effect on extent of absorption.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Etodolac is extensively metabolized in the liver. Renal elimination of etodolac and its metabolites is the primary route of excretion (72%). Metabolites found in urine (with percents of the administered dose) are: unchanged etodolac (1%), etodolac glucuronide (13%), hydroxylated metabolites (6-, 7-, and 8-OH; 5%), hydroxylated metabolite glucuronides (20%), and unidentified metabolites (33%). Fecal excretion accounts for 16% of its elimination.

Source: Drug Bank

Protein Binding

> 99% bound, primarily to albumin

Source: Drug Bank

Absorption

Based on mass balance studies, the systemic bioavailability of etodolac from either the tablet or capsule formulation is at least 80%.

Source: Drug Bank

Half-Life

Terminal t 1/2, 7.3 +/- 4.0 hours. Distribution t 1/2, 0.71 +/- 0.50 hours

Source: Drug Bank

Toxicity

Selective COX-2 inhibitors have been associated with increased risk of serious cardiovascular events (e.g. myocardial infarction, stroke) in some patients. Current data is insufficient to assess the cardiovascular risk of etodolac. Etodolac may increase blood pressure and/or cause fluid retention and edema. Risk of GI toxicity including bleeding, ulceration and perforation. Risk of direct renal injury, including renal papillary necrosis. Anaphylactoid and serious skin reactions (e.g. exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported. Common adverse events include abdominal pain, constipation, diarrhea, dyspepsia, flatulence, GI bleeding, GI perforation, nausea, peptic ulcer, vomiting, renal function abnormalities, anemia, dizziness, edema, liver function test abnormalities, headache, prolonged bleeding time, pruritus, rash, tinnitus. Symptoms of overdose include lethargy, drowsiness, nausea, vomiting, and epigastric pain.

Source: Drug Bank

Clearance

Source: Drug Bank

Route of Elimination

It is not known whether etodolac is excreted in human milk; however, based on its physical-chemical properties, excretion into breast milk is expected. Etodolac is extensively metabolized in the liver. The hydroxylated-etodolac metabolites undergo further glucuronidation followed by renal excretion and partial elimination in the feces (16% of dose). Approximately 1% of a etodolac dose is excreted unchanged in the urine with 72% of the dose excreted into urine as parent drug plus metabolite.

Source: Drug Bank

Volume of Distribution

  • 390 mL/kg

Source: Drug Bank

Chemical Properties

Chemical Formula

C17H21NO3

Source: Drug Bank

Isomeric SMILES

CCc1cccc2c1[nH]c3c2CCOC3(CC)CC(=O)O

Source: OpenEye

Canonical SMILES

CCC1=C2NC3=C(CCOC3(CC)CC(O)=O)C2=CC=C1

Source: Drug Bank

Average Molecular Weight

287.3535

Source: Drug Bank

Monoisotopic Molecular Weight

287.152143543

Source: Drug Bank

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Drug Targets

Gene Description
ALB (source: Drug Bank)
PTGS1 (source: Drug Bank)
PTGS2 (source: Drug Bank)
RXRA (source: Drug Bank)

Drug Interactions

Drug Description
etodolac Monitor for nephrotoxicity (source: Drug Bank)
etodolac Monitor for nephrotoxicity (source: Drug Bank)
acenocoumarol The NSAID increases the anticoagulant effect (source: Drug Bank)
acenocoumarol The NSAID, etodolac, may increase the anticoagulant effect or acenocoumarol. (source: Drug Bank)
alendronate Increased risk of gastric toxicity (source: Drug Bank)
alendronate Increased risk of gastric toxicity (source: Drug Bank)
anisindione The NSAID, etodolac, may increase the anticoagulant effect of anisindione. (source: Drug Bank)
cyclosporine Monitor for nephrotoxicity (source: Drug Bank)
cyclosporine Monitor for nephrotoxicity (source: Drug Bank)
dicumarol The NSAID increases the anticoagulant effect (source: Drug Bank)
dicumarol The NSAID, etodolac, may increase the anticoagulant effect of dicumarol. (source: Drug Bank)
methotrexate The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The NSAID, etodolac, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity. (source: Drug Bank)
warfarin The NSAID increases the anticoagulant effect (source: Drug Bank)
warfarin The NSAID, etodolac, may increase the anticoagulant effect of warfarin. (source: Drug Bank)
etodolac Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided. (source: Drug Bank)
etodolac The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
etodolac The NSAID, etodolac, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity. (source: Drug Bank)
etodolac The NSAID, Etodolac, may antagonize the antihypertensive effect of Timolol. (source: Drug Bank)
etodolac The NSAID, Etodolac, may antagonize the antihypertensive effect of Timolol. (source: Drug Bank)
etodolac The NSAID, Etodolac, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Etodolac is initiated, discontinued or dose changed. (source: Drug Bank)
etodolac The prostacyclin analogue, Treprostinil, may increase the risk of bleeding when combined with the NSAID, Etodolac. Monitor for increased bleeding during concomitant thearpy. (source: Drug Bank)
etodolac The antiplatelet effects of etodolac may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy. (source: Drug Bank)

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
Contraindicated With

Publications related to etodolac: 1

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation. Analytical and bioanalytical chemistry. 2008. Zanger Ulrich M, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0228-2599-11
DrugBank:
DB00749
ChEBI:
4909
KEGG Drug:
D00315
PubChem Compound:
3308
PubChem Substance:
179980
46505184
Drugs Product Database (DPD):
2242915
BindingDB:
50016799
ChemSpider:
3192
Therapeutic Targets Database:
DAP000778
FDA Drug Label at DailyMed:
a8984705-a43a-4977-808a-44df42930de1

Clinical Trials

These are trials that mention etodolac and are related to either pharmacogenetics or pharmacogenomics.

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Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.