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| Name | Etodolac | ||||||||||||||||||||||||||||||||||||
| Accession Number | DB00749 (APRD00067) | ||||||||||||||||||||||||||||||||||||
| Type | small molecule | ||||||||||||||||||||||||||||||||||||
| Groups | approved | ||||||||||||||||||||||||||||||||||||
| 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. |
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| Structure |
Download: MOL | SDF | SMILES | InChI Display: 2D Structure | 3D Structure |
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| Synonyms |
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| Brand name mixtures | Not Available | ||||||||||||||||||||||||||||||||||||
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| CAS number | 41340-25-4 | ||||||||||||||||||||||||||||||||||||
| Weight |
Average: 287.3535 Monoisotopic: 287.152143543 |
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| Chemical Formula | C17H21NO3 | ||||||||||||||||||||||||||||||||||||
| InChI Key | InChIKey=NNYBQONXHNTVIJ-UHFFFAOYSA-N | ||||||||||||||||||||||||||||||||||||
| InChI |
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)
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| IUPAC Name |
2-{1,8-diethyl-1H,3H,4H,9H-pyrano[3,4-b]indol-1-yl}acetic acid
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| SMILES |
CCC1=CC=CC2=C1NC1=C2CCOC1(CC)CC(O)=O
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| Mass Spec | Not Available | ||||||||||||||||||||||||||||||||||||
| Taxonomy | |||||||||||||||||||||||||||||||||||||
| Kingdom | Organic | ||||||||||||||||||||||||||||||||||||
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| Substructures |
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| Pharmacology | |||||||||||||||||||||||||||||||||||||
| Indication | For acute and long-term management of signs and symptoms of osteoarthritis and rheumatoid arthritis, as well as for the management of pain. | ||||||||||||||||||||||||||||||||||||
| Pharmacodynamics | 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. | ||||||||||||||||||||||||||||||||||||
| 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. | ||||||||||||||||||||||||||||||||||||
| Absorption | Based on mass balance studies, the systemic bioavailability of etodolac from either the tablet or capsule formulation is at least 80%. | ||||||||||||||||||||||||||||||||||||
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| Protein binding | > 99% bound, primarily to albumin | ||||||||||||||||||||||||||||||||||||
| Metabolism |
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.
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| 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. | ||||||||||||||||||||||||||||||||||||
| Half life | Terminal t1/2, 7.3 ± 4.0 hours. Distribution t1/2, 0.71 ± 0.50 hours | ||||||||||||||||||||||||||||||||||||
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| 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. | ||||||||||||||||||||||||||||||||||||
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| Patents | Not Available | ||||||||||||||||||||||||||||||||||||
| Properties | |||||||||||||||||||||||||||||||||||||
| State | solid | ||||||||||||||||||||||||||||||||||||
| Melting point | 145-148 oC | ||||||||||||||||||||||||||||||||||||
| Experimental Properties |
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| Predicted Properties |
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| Synthesis Reference | Not Available | ||||||||||||||||||||||||||||||||||||
| General Reference | Not Available | ||||||||||||||||||||||||||||||||||||
| External Links |
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| ATC Codes |
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| PDB Entries | Not Available | ||||||||||||||||||||||||||||||||||||
| FDA label | show (289.6 KB) | ||||||||||||||||||||||||||||||||||||
| MSDS | Not Available | ||||||||||||||||||||||||||||||||||||
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| Drug Interactions | Not Available | ||||||||||||||||||||||||||||||||||||
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| Targets |
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1. Prostaglandin G/H synthase 2 Pharmacological action: yesActions: inhibitor May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity Organism class: humanUniProt ID: P35354 ![]() Gene: PTGS2 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
2. Prostaglandin G/H synthase 1 Pharmacological action: unknownActions: inhibitor May play an important role in regulating or promoting cell proliferation in some normal and neoplastically transformed cells Organism class: humanUniProt ID: P23219 ![]() Gene: PTGS1 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
3. Retinoic acid receptor RXR-alpha Pharmacological action: unknownActions: other Nuclear hormone receptor. Involved in the retinoic acid response pathway. Binds 9-cis retinoic acid (9C-RA). ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer Organism class: humanUniProt ID: P19793 ![]() Gene: RXRA ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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| Enzymes |
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Actions: substrate, inhibitor
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan UniProt ID: P11712![]() Gene: CYP2C9 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
2. UDP-glucuronosyltransferase 1-9 Actions: substrateUDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols UniProt ID: O60656![]() Gene: UGT1A9 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
3. UDP-glucuronosyltransferase 1-3 Actions: substrateUDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds UniProt ID: P35503![]() Gene: UGT1A3 ![]() Protein Sequence: FASTA SNPs: SNPJam Report ![]() References:
4. UDP-glucuronosyltransferase 1-10 Actions: substrateUDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds UniProt ID: Q9HAW8![]() Gene: UGT1A10 ![]() Protein Sequence: FASTA SNPs: SNPJam Report ![]() References:
5. UDP-glucuronosyltransferase 2B7 Actions: substrateIts unique specificity for 3,4-catechol estrogens and estriol suggests it may play an important role in regulating the level and activity of these potent and active estrogen metabolites UniProt ID: P16662![]() Gene: UGT2B7 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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| Transporters |
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1. Solute carrier family 22 member 6 Actions: inhibitorUniProt ID: Q4U2R8 ![]() Gene: hROAT1 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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| Carriers |
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Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood UniProt ID: P02768![]() Gene: ALB ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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| Comments |
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This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.