아세메타신-D4

Pharmaceuticals -> Analgesics and anti-inflammatories

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Used in Switzerland

Pharmaceuticals

Slightly soluble

>62.4 [ug/mL] (The mean of the results at pH 7.4)

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

Pharmaceuticals

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

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

Danger

H300 (100%): Fatal if swallowed [Danger Acute toxicity, oral]

P260, P262, P264, P270, P271, P280, P284, P301+P316, P302+P352, P304+P340, P316, P320, P321, P330, P361+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 65 reports by companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

ACEMETACIN

DILI Positive

DOI:10.1016/j.drudis.2019.09.022

M01AB11

M - Musculo-skeletal system

QM - Musculo-skeletal system

The effect of acemetacin causes a weak reduction of prostaglandin synthesis which generates an anti-inflammatory and analgesic effect. The weak inhibition of prostaglandin reduces significantly the damage caused in the mucous membrane of the gastrointestinal tract. Studies have shown that acemetacin strongly inhibits the release of histamine from mast cells and the generation of hyperthermia. Acemetacin effect also causes changes in systolic and diastolic blood pressure as well as inhibition of platelet aggregation.

Acemetacin is a non-selective inhibitor of the production of pro-inflammatory mediators derived from the action of the enzyme COX. COX is essential for the synthesis of prostaglandin E2 and F2 which are molecules derived from fatty acids and stored in the cell membrane. Acetometacine is metabolized and forms its major metabolite indometacin which is also a non-selective inhibitor of COX and exhibits the capacity to inhibit the motility of polymorphonuclear leukocytes and decreased cerebral flow by modulating the nitric oxide pathway and vasoconstriction.

Acemetacin is highly metabolized and degraded by esterolytic cleavage to form its major and active metabolite indometacin. It presents other inactive metabolites made by reaction of O-demethylation, N-desacylation and part of them are also transformed by conjugation with glucuronic acid.

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.

After 8 days of oral administration twice daily of acemetacin there was an age-dependant Cmax of 276.8 ng/ml in elderly compared to 187 ng/ml for younger individuals. There was also a Tmax of 2.5 h and AUC in a range of 483-712 ng h/ml. The bioavailability of acemetacin after repeated doses is aproximately 66% in plasma and 64% in urine.

The elimination of acemetacin is divided in renal elimination that covers 40% of the complete administered dose and the restant 60% is excreted in feces.

The apparent volume of distribution of acemetacin is in a range of 0.5-0.7 L/kg.

Intravenous administration of acemetacin in healthy subjects reported a clearance rate of 4.59 ml min/kg.