エトドラク

DEA NFLIS-Drug Category -> Analgesics

Pharmaceuticals

Pharmaceuticals -> Used in Switzerland

2.5

2.75

Breast Feeding; Lactation; Milk, Human; Analgesic Agents; Anti-inflammatory Agents, Nonsteroidal

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Pharmaceuticals

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

163.36 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Danger

H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]

P203, P264, P264+P265, P270, P280, P301+P316, P305+P351+P338, P318, P321, P330, P337+P317, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 50 reports by companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Hazard Traits - Developmental Toxicity; Reproductive Toxicity

Etodolac: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right.

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 (greater than 3 fold elevated) occur in less than 1% of patients.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Etodolac

vMost-DILI-concern

8

Warnings & precautions

DOI:10.1016/j.drudis.2016.02.015

◉ Summary of Use during Lactation

◈ What is etodolac?

M - Musculo-skeletal system

QM - Musculo-skeletal system

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 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.

2M36281008

ETODOLAC

Mechanisms of Action [MoA] - Cyclooxygenase Inhibitors

Chemical Structure [CS] - Anti-Inflammatory Agents, Non-Steroidal

Established Pharmacologic Class [EPC] - Nonsteroidal Anti-inflammatory Drug

Etodolac is a Nonsteroidal Anti-inflammatory Drug. The mechanism of action of etodolac is as a Cyclooxygenase Inhibitor.

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.

A subclass of cyclooxygenase inhibitors with specificity for CYCLOOXYGENASE-2.

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]

Animal Drugs -> FDA Approved Animal Drug Products (Green Book) -> Active Ingredients

Pharmaceuticals