QuickView for Etodolac (compound)

Summary
General Info

PubChem

PubChem Compound 174620

Name:	Etodolac
PubChem Compound ID:	174620
Description:	A nonsteroidal anti-inflammatory agent with potent analgesic and antiarthritic properties. It has been shown to be effective in the treatment of OSTEOARTHRITIS; RHEUMATOID ARTHRITIS; ankylosing SPONDYLITIS; and in the alleviation of postoperative pain (PAIN, POSTOPERATIVE).
Molecular formula:	C₁₇H₂₁NO₃
Molecular weight:	287.354 g/mol
Synonyms:	Pyrano(3,4-b)indole-1-acetic acid, 1,3,4,9-tetrahydro-1,8-diethyl-, (R)-; 87226-41-3; (-)-Etodolic acid; BRN 5761989; (-)-1,8-Diethyl-1,3,4,9-tetrahydropyrano(3,4-b)indole-1-acetic acid; RAK-593

DrugBank

Identification

Name:	Etodolac
Name (isomeric):	DB00749
Drug Type:	small molecule
Description:	A nonsteroidal anti-inflammatory agent with potent analgesic and antiarthritic properties. It has been shown to be effective in the treatment of OSTEOARTHRITIS; RHEUMATOID ARTHRITIS; ankylosing SPONDYLITIS; and in the alleviation of postoperative pain (PAIN, POSTOPERATIVE).
Brand:	Lodine, Lodine XL, Etodolacum [INN-Latin], Etodolacetodolic acid, Etodolac [Usan:Ban:Inn], Etodolaco [INN-Spanish], Ultradol, Etodolic Acid
Category:	Analgesics, Non-Narcotic, Antipyretics, Cyclooxygenase Inhibitors, Analgesics, Anti-inflammatory Agents, Nonsteroidal Anti-inflammatory Agents (NSAIAs)
CAS number:	41340-25-4

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.
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 racema... show more » 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. show less «
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 a... show more » 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. show less «
Absorption:	Based on mass balance studies, the systemic bioavailability of etodolac from either the tablet or capsule formulation is at least 80%.
Protein binding:	> 99% bound, primarily to albumin
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.
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 t_1/2, 7.3 ± 4.0 hours. Distribution t_1/2, 0.71 ± 0.50 hours
Clearance:	Oral cl=49.1 mL/h/kg [Normal healthy adults] Oral cl=49.4 mL/h/kg [Healthy males (18-65 years)] Oral cl=35.7 mL/h/kg [Healthy females (27-65 years)] Oral cl=45.7 mL/h/kg [Eldery (>65 years)] Oral cl=58.3 mL/h/kg [Renal impairement (46-73 years)] Oral cl=42.0 mL/h/kg [Hepatic impairement (34-60 years)]
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.
Affected organisms:	Humans and other mammals

Interactions

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.

Drug interaction:

Acenocoumarol	The NSAID, etodolac, may increase the anticoagulant effect or acenocoumarol.
Trandolapril	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.
Anisindione	The NSAID, etodolac, may increase the anticoagulant effect of anisindione.
Methotrexate	The NSAID, etodolac, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Ginkgo biloba	Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.

Targets

Prostaglandin G/H synthase 2

Prostaglandin G/H synthase 1

Retinoic acid receptor RXR-alpha

Enzymes

Cytochrome P450 2C9

UDP-glucuronosyltransferase 1-9

UDP-glucuronosyltransferase 1-3

UDP-glucuronosyltransferase 1-10

UDP-glucuronosyltransferase 2B7

Transporters

Solute carrier family 22 member 6

Carriers

Serum albumin