化合物信息

Drug Groups

approved; investigational

Description

Indomethacin is a non-steroidal antiinflammatory agent (NSAIA) with antiinflammatory, analgesic and antipyretic activity. Its pharmacological effect is thought to be mediated through inhibition of the enzyme cyclooxygenase (COX), the enzyme responsible for catalyzes the rate-limiting step in prostaglandin synthesis via the arachidonic acid pathway.

Indication

For moderate to severe rheumatoid arthritis including acute flares of chronic disease, ankylosing spondylitis, osteoarthritis, acute painful shoulder (bursitis and/or tendinitis) and acute gouty arthritis.

Pharmacology

Indomethacin, a NSAIA, with analgesic and antipyretic properties exerts its pharmacological effects by inhibiting the synthesis of prostaglandins involved in pain, fever, and inflammation. Indomethacin inhibits the catalytic activity of the COX enzymes, the enzymes responsible for catalyzing the rate-limiting step in prostaglandin synthesis via the arachidonic acid pathway. Indomethacin is known to inhibit two well-characterized isoforms of COX, COX-1 and COX-2, with greater selectivity for COX-1. COX-1 is a constitutively expressed enzyme that is involved in gastric mucosal protection, platelet and kidney function. It catalyzes the conversion of arachidonic acid to prostaglandin (PG) G2 and PGG2 to PGH2. COX-1 is involved in the synthesis pathways of PGE2, PGD2, PDF2a, PGI2 (also known as prostacyclin) and thromboxane A2 (TXA2). COX-2 is constitutively expressed and highly inducible by inflammatory stimuli. It is found in the central nervous system, kidneys, uterus and other organs. It also catalyzes the conversion of arachidonic acid to PGG2 and PGG2 to PGH2. In the COX-2-mediated pathway, PGH2 is subsequently converted to PGE2 and PGI2 (also known as prostacyclin). PGE2 is involved in mediating inflammation, pain and fever. Decreasing levels of PGE2 leads to decreased inflammation.

Toxicity

The following symptoms may be observed following overdosage: nausea, vomiting, intense headache, dizziness, mental confusion, disorientation, or lethargy. There have been reports of paresthesias, numbness, and convulsions. The oral LD₅₀ of indomethacin in mice and rats (based on 14 day mortality response) was 50 and 12 mg/kg, respectively.

Affected Organisms

Biotransformation

Hepatic.

Absorption

Bioavailability is approximately 100% following oral administration and 80–90% following rectal administration.

Half Life

4.5 hours

Protein Binding

97%

Elimination

Indomethacin is eliminated via renal excretion, metabolism, and biliary excretion.

References

External Links