Etodolac | 41340-25-4, Etodolac Formula

Description

Etodolac is a non-steroidal anti-inflammatory compound that is a non-selective inhibitor of COX (IC50=53.5 nM)IC50 value: 53.5 nMTarget: COX1; COX2Post-marketing studies demonstrated that etodolac inhibition of cyclooxygenase is somewhat COX-2 selective similar to celecoxib and other "COX-2 inhibitors." Unlike rofecoxib, both etodolac and celecoxib can fully inhibit COX-1 and are designated as having "preferential selectivity" toward COX-2. The (inactive against COX) r-enantiomer of etod

Solid

Etodolac is a monocarboxylic acid that is acetic acid in which one of the methyl hydrogens is substituted by a 1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-yl moiety. A preferential inhibitor of cyclo-oxygenase 2 and non-steroidal anti-inflammatory, it is used for the treatment of rheumatoid arthritis and osteoarthritis, and for the alleviation of postoperative pain. Administered as the racemate, only the (S)-enantiomer is active. It has a role as a non-steroidal anti-inflammatory drug, a cyclooxygenase 2 inhibitor, a non-narcotic analgesic and an antipyretic. It is a monocarboxylic acid and an organic heterotricyclic compound.|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.|Etodolac is a nonsteroidal antiinflammatory drug (NSAID) that is available by prescription only and is used long term for therapy of chronic arthritis and short term for acute pain. Etodolac has been linked to rare instances of clinically apparent drug induced liver disease.|A non-steroidal anti-inflammatory agent and cyclooxygenase-2 (COX-2) inhibitor with potent analgesic and anti-arthritic 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).

Etodolac Basic Attributes

Molecular Weight：

287.35

Exact Mass：

287.35

EC Number：

1312995-182-4

NSC Number：

757821|282126

DSSTox ID：

DTXSID9020615

ATC Code：

M - Musculo-skeletal system

HScode：

2934999090

Characteristics

PSA：

62.3

XLogP3：

2.8

Appearance：

crystalline solid

Density：

1.2±0.1 g/cm3

Melting Point：

146.5 °C

Boiling Point：

507.9ºC at 760 mmHg

Flash Point：

261.0±28.7 °C

Refractive Index：

1.597

Water Solubility：

40mg/L(37 ºC)

Storage Conditions：

2-8°C

Dissociation Constants：

4.65

Collision Cross Section：

164.4 Å² [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

Safety Information

Packing level：

III

Hazard category：

6.1(b)

Transport codes：

3249

wgk germany：

3

hazard class code：

23/24/25-40-36-25-36/37/38

safety instructions：

22-36-45-26-36/37

RTECS Number：

UQ0360000

Marks：

T,Xi

Stability/Shelf Life：

Stable at normal temperatures and pressures.

Precautionary statement(s)：

Missing Phrase - N15.00950417-P305 + P351 + P338

Hazard Statements：

H301-H319

GHS Classification：

|Danger|H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]|P201, P202, P264, P270, P280, P281, P301+P310, P305+P351+P338, P308+P313, P321, P330, P337+P313, P405, and P501|Aggregated GHS information provided by 49 companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Toxicity

Toxicity Summary：

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.

Hepatotoxicity：

Prospective studies show that 1% to 2% of patients taking etodolac experience at least transient serum aminotransferase elevations. These may resolve even with drug continuation. Marked aminotransferase elevations (>3 fold elevated) occur in

Protein Binding：

> 99% bound, primarily to albumin

Drug Information

Drug Indication：

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

LiverTox Summary：

Etodolac is a nonsteroidal antiinflammatory drug (NSAID) that is available by prescription only and is used long term for therapy of chronic arthritis and short term for acute pain. Etodolac has been linked to rare instances of clinically apparent drug induced liver disease.

Drug Classes：

Nonsteroidal Antiinflammatory Drugs

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_.

MeSH：

A subclass of cyclooxygenase inhibitors with specificity for CYCLOOXYGENASE-2. (See all compounds classified as Cyclooxygenase 2 Inhibitors.)|Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects. (See all compounds classified as Anti-Inflammatory Agents, Non-Steroidal.)

Absorption：

Based on mass balance studies, the systemic bioavailability of etodolac from either the tablet or capsule formulation is at least 80%.|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.|390 mL/kg|Oral cl=49.1 mL/h/kg [Normal healthy adults]

Metabolism/Metabolites：

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.|Etodolac has known human metabolites that include (2S,3S,4S,5R)-6-[2-(1,8-Diethyl-4,9-dihydro-3H-pyrano[3,4-b]indol-1-yl)acetyl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid.

Biological Half-Life：

Terminal t_1/2, 7.3 ± 4.0 hours. Distribution t_1/2, 0.71 ± 0.50 hours

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.

MeSH Entry Terms：

AY 24,236

Etodolac Use and Manufacturing

Methods of Manufacturing

O-Ethylaniline reacts with trichloroacetaldehyde hydrate and hydroxylamine to form oxime during acylation, then cyclizes under the catalysis of sulfuric acid, and reduces it with lithium aluminum hydride to generate indole derivatives, and reacts with oxalyl chloride and ethanol in 3 The 1, 2-dicarbonyl side chain is introduced at the position, lithium aluminum hydride is reduced to hydroxyethyl, and condensed and fused with ethyl propionyl acetate, and finally hydrolyzed to produce etodolac.

Uses

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

Use Classification：

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Animal Drugs -> FDA Approved Animal Drug Products (Green Book) -> Active Ingredients|Pharmaceuticals

Computed Properties

Molecular Weight:287.35
XLogP3:2.8
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:4
Exact Mass:287.15214353
Monoisotopic Mass:287.15214353
Topological Polar Surface Area:62.3
Heavy Atom Count:21
Complexity:400
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes

Drug Function and Efficacy

This product is a non-steroidal anti-inflammatory drug with anti-inflammatory, antipyretic and analgesic effects. Its mechanism of action may be to inhibit the synthesis of prostaglandins (PG) by blocking the activity of cyclooxygenase.

This ingredient has been used in drugs with the following functions (note: it does not mean that the ingredient itself has the following health functions)

Related Drugs

Etodolac Tablets
Ingredients	The main ingredient of this product is etodolac, whose chemical name is (plusmn;) 1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid.
Indication	Antacids: Taking antacids at the same time has no significant effect on the absorption of etodolac. However, antacids can reduce the peak concentration of etodolac by 15-20%, but it does not affect the time to peak. Aspirin: When etodolac is used together with aspirin, although the clearance of free etodolac does not change, its protein binding rate decreases. The clinical significance of this drug interaction is still unclear. However, due to the increased potential adverse reactions when the two are used together, this usage is not recommended clinically. Warfarin: The simultaneous use of etodolac and warfarin can reduce the protein binding rate of warfarin, but it does not affect the clearance of free warfarin and prothrombin. time, so the combination of the two drugs does not require adjustment of the dose of either drug. However, some post-marketing reports show that the combination of the two drugs prolongs the prothrombin time, so they should be used with caution. Phenytoin sodium: There is no obvious pharmacokinetic interaction between etodolac and phenytoin sodium. Glyburide: When etodolac is used in combination with glyburide, there is no significant change in pharmacokinetics and pharmacodynamics. Diuretics: In healthy volunteers, there is no obvious pharmacokinetic interaction between etodolac and furosemide or hydrochlorothiazide, and etodolac will not weaken the diuretic effect of diuretics. However, in patients who have taken diuretics or suffer from heart, kidney, or liver failure, the two Be careful when using these drugs together. Methotrexate: There is no obvious pharmacokinetic interaction between etodolac and methotrexate. Cyclosporine, digoxin and lithium: Etodolac inhibits the synthesis of prostaglandins, which changes the kidney's clearance of these drugs, increases drug concentrations and increases toxicity. Cyclosporine-related renal toxicity will also increase. Therefore, patients who have taken these drugs should be closely monitored for possible drug toxicity when receiving etodolac or other NSAIDs, especially those with impaired renal function. Protein binding: In vitro research data show that ibuprofen, acetaminophen, phenytoin, probenecid, indomethacin, chlorosulfuron Propionamide, glyburide, naproxen, glipizide, and piroxicam have no significant effect on the proportion of free etodolac. On the contrary, phenylbutazone increases the free concentration (about 80%). Although in vivo tests have not confirmed whether phenylbutazone changes the clearance of etodolac, its co-administration is not recommended clinically. Laboratory test interactions: Phenolic metabolites of etodolac will appear in the urine of patients taking etodolac, so false positive reactions may occur in the determination of urine bilirubin. Rapid diagnostic methods have found false positive reactions in urine ketone bodies in some patients taking etodolac. This phenomenon is not related to other clinical conditions and is unrelated to the dosage.
Specifications	0.4g
Manufacturer	Zhejiang Yatai Pharmaceutical Co., Ltd.

Etodolac Capsules
Ingredients	Etodolac.
Indication	1. Antacids: Taking antacids at the same time has no significant effect on the absorption of etodolac, but it can reduce the peak concentration of etodolac by 15%-20%, but it does not affect the time to peak. 2. Aspirin: When etodolac is used in combination with aspirin, although the clearance of free etodolac does not change, its protein binding rate decreases. The clinical significance of this drug interaction is still unclear, but due to the increased potential adverse reactions when the two are used together, this usage is not recommended clinically. 3. Warfarin: The simultaneous use of etodolac and warfarin can reduce the protein binding rate of warfarin, but does not affect the clearance of free warfarin and the prothrombin time. Therefore, there is no need to adjust the dose of either drug when the two drugs are used together. However, some post-marketing reports show that the combination of the two drugs prolongs the prothrombin time.
Specifications	0.2g

Etodolac Tablets
Ingredients	Active ingredient: Etodolac.
Indication	Antacids: Taking antacids at the same time has no significant effect on the absorption of etodolac. However, antacids can reduce the peak concentration of etodolac by 15-20%, but it does not affect the time to peak. Aspirin: When etodolac is used together with aspirin, although the clearance of free etodolac does not change, its protein binding rate decreases. The clinical significance of this drug interaction is still unclear. However, due to the increased potential adverse reactions when the two are used together, this usage is not recommended clinically. Warfarin: The simultaneous use of etodolac and warfarin can reduce the protein binding rate of warfarin, but it does not affect the clearance of free warfarin and prothrombin. time, so the combination of the two drugs does not require adjustment of the dose of either drug. However, some post-marketing reports show that the combination of the two drugs prolongs the prothrombin time, so they should be used with caution. Phenytoin sodium: There is no obvious pharmacokinetic interaction between etodolac and phenytoin sodium. Glyburide: When etodolac is used in combination with glyburide, there is no significant change in pharmacokinetics and pharmacodynamics. Diuretics: In healthy volunteers, there is no obvious pharmacokinetic interaction between etodolac and furosemide or hydrochlorothiazide, and etodolac will not weaken the diuretic effect of diuretics. However, in patients who have taken diuretics or suffer from heart, kidney, or liver failure, the two Be careful when using these drugs together. Methotrexate: There is no obvious pharmacokinetic interaction between etodolac and methotrexate. Cyclosporine, digoxin and lithium: Etodolac inhibits the synthesis of prostaglandins, which changes the kidney's clearance of these drugs, increases drug concentrations and increases toxicity. Cyclosporine-related renal toxicity will also increase. Therefore, patients who have taken these drugs should be closely monitored for possible drug toxicity when receiving etodolac or other NSAIDs, especially those with impaired renal function. Protein binding: In vitro research data show that ibuprofen, acetaminophen, phenytoin, probenecid, indomethacin, chlorosulfuron Propionamide, glyburide, naproxen, glipizide, and piroxicam have no significant effect on the proportion of free etodolac. On the contrary, phenylbutazone increases the free concentration (about 80%). Although in vivo tests have not confirmed whether phenylbutazone changes the clearance of etodolac, its co-administration is not recommended clinically. Laboratory test interactions: Phenolic metabolites of etodolac will appear in the urine of patients taking etodolac, so false positive reactions may occur in the determination of urine bilirubin. Rapid diagnostic methods have found false positive reactions in urine ketone bodies in some patients taking etodolac. This phenomenon is not related to other clinical conditions and is unrelated to the dosage.
Specifications	0.2g
Manufacturer	Zhejiang Yatai Pharmaceutical Co., Ltd.

See More Related Drugs

Registered Holders

ULKAR KIMYA SANAYII VE TICARET AS

United States
Active
Pharmaceutical Works Polpharma S.A.

Japan
Active
KREATIVE ACTIVES PRIVATE LIMITED

India
Active

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