Tìm theo
Indomethacin
Các tên gọi khác (9 ) :
  • {1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetic acid
  • 1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetic acid
  • Aconip
  • Indocin
  • Indometacin
  • Indometacina
  • Indometacine
  • Indometacinum
  • Indomethacin
Thuốc giảm đau, hạ sốt, chống viêm không steroid, điều trị Gút và các bệnh xương khớp
Thuốc Gốc
Small Molecule
CAS: 53-86-1
ATC: M01AB01, C01EB03
ĐG : Advanced Pharmaceutical Services Inc.
CTHH: C19H16ClNO4
PTK: 357.788
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.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C19H16ClNO4
Phân tử khối
357.788
Monoisotopic mass
357.076785712
InChI
InChI=1S/C19H16ClNO4/c1-11-15(10-18(22)23)16-9-14(25-2)7-8-17(16)21(11)19(24)12-3-5-13(20)6-4-12/h3-9H,10H2,1-2H3,(H,22,23)
InChI Key
InChIKey=CGIGDMFJXJATDK-UHFFFAOYSA-N
IUPAC Name
2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetic acid
Traditional IUPAC Name
indomethacin
SMILES
COC1=CC2=C(C=C1)N(C(=O)C1=CC=C(Cl)C=C1)C(C)=C2CC(O)=O
Độ tan chảy
151
Độ hòa tan
0.937 mg/L (at 25 °C)
logP
4.27
logS
-4.62
pKa (strongest acidic)
3.8
pKa (Strongest Basic)
-2.3
PSA
68.53 Å2
Refractivity
94.81 m3·mol-1
Polarizability
36.64 Å3
Rotatable Bond Count
4
H Bond Acceptor Count
4
H Bond Donor Count
1
Physiological Charge
-1
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
caco2 Permeability
-4.69
pKa
4.5
Dược Lực Học : 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.
Cơ Chế Tác Dụng : 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. Indomethacin is a prostaglandin G/H synthase (also known as cyclooxygenase or COX) inhibitor that acts on both prostaglandin G/H synthase 1 and 2 (COX-1 and -2). Prostaglandin G/H synthase catalyzes the conversion of arachidonic acid to a number of prostaglandins involved in fever, pain, swelling, inflammation, and platelet aggregation. Indomethacin antagonizes COX by binding to the upper portion of the active site, preventing its substrate, arachidonic acid, from entering the active site. Indomethacin, unlike other NSAIDs, also inhibits phospholipase A2, the enzyme responsible for releasing arachidonic acid from phospholipids. Indomethacin is more selective for COX-1 than COX-2, which accounts for its increased adverse gastric effects relative to other NSAIDs. COX-1 is required for maintaining the protective gastric mucosal layer. The analgesic, antipyretic and anti-inflammatory effects of indomethacin occur as a result of decreased prostaglandin synthesis. Its antipyretic effects may be due to action on the hypothalamus, resulting in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation.
Dược Động Học :
▧ Absorption :
Bioavailability is approximately 100% following oral administration and 80–90% following rectal administration.
▧ Protein binding :
97%
▧ Metabolism :
Hepatic.
▧ Route of Elimination :
Indomethacin is eliminated via renal excretion, metabolism, and biliary excretion.
▧ Half Life :
4.5 hours
Độc Tính : 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.
Chỉ Định : 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.
Tương Tác Thuốc :
  • Acebutolol Risk of inhibition of renal prostaglandins
  • Acenocoumarol The NSAID, indomethacin, may increase the anticoagulant effect of acenocoumarol.
  • Alendronate Increased risk of gastric toxicity
  • Anisindione The NSAID, indomethacin, may increase the anticoagulant effect of anisindione.
  • Atenolol Risk of inhibition of renal prostaglandins
  • Azilsartan medoxomil Increases toxicity of each. May deteriorate renal function, particularly in volume depleted or elderly patients. Decreases effects of azilsartan by antagonism.
  • Betaxolol Nonsteroidal Anti-Inflammatory Agents such as indomethacin may diminish the antihypertensive effect of Beta-Blockers such as betaxolol. Monitor for increases in blood pressure if a nonsteroidal anti-inflammatory agent (NSAID) is initiated/dose increased, or decreases in blood pressure if a NSAID is discontinued/dose decreased; this is particularly important if NSAID treatment is for extended periods of time. Ophthalmic beta-blockers are likely of little concern.
  • Bevantolol Risk of inhibition of renal prostaglandins
  • Bisoprolol Risk of inhibition of renal prostaglandins
  • Bumetanide The NSAID, indomethacin, may decrease the diuretic and antihypertensive effects of the loop diuretic, bumetanide.
  • Carteolol Risk of inhibition of renal prostaglandins
  • Carvedilol Risk of inhibition of renal prostaglandins
  • Colesevelam Bile acid sequestrants may decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. Monitor for decreased serum concentrations/therapeutic effects of nonsteroidal anti-inflammatory agents (NSAID) if coadministered with bile acid sequestrants. Separating the administration of doses by 2 or more hours may reduce (but not eliminate) the risk of interaction. The manufacturer of colesevelam recommends that drugs should be administered at least 1 hour before or 4 hours after colesevelam.
  • Cyclosporine Monitor for nephrotoxicity
  • Dicoumarol The NSAID, indomethacin, may increase the anticoagulant effect of dicumarol.
  • Diflunisal Concomitant therapy with the two NSAIDs, indomethacin and diflunisal, increases the risk of NSAID-related adverse effects (e.g. GI ulcers, bleeds, increased blood pressure).
  • Eltrombopag Increases levels of Indomethacin via metabolism decrease. UDP-glucuronosyltransferase inhibition with unclear significance.
  • Esmolol Risk of inhibition of renal prostaglandins
  • Ethacrynic acid The NSAID, indomethacin, may decrease the diuretic and antihypertensive effects of the loop diuretic, ethacrynic acid.
  • Furosemide The NSAID, indomethacin, may decrease the diuretic and antihypertensive effects of the loop diuretic, furosemide.
  • Ginkgo biloba Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
  • Glucagon recombinant Monitor therapy due to diminished therapeutic effect of glucagon.
  • Labetalol Risk of inhibition of renal prostaglandins
  • Lithium The NSAID, indomethacin, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.
  • Losartan Indomethacin decreases the effect of losartan
  • Methotrexate The NSAID, indomethacin, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
  • Metoprolol Risk of inhibition of renal prostaglandins
  • Nadolol Risk of inhibition of renal prostaglandins
  • Oxprenolol Risk of inhibition of renal prostaglandins
  • Penbutolol Risk of inhibition of renal prostaglandins
  • Pindolol Risk of inhibition of renal prostaglandins
  • Practolol Risk of inhibition of renal prostaglandins
  • Pralatrexate NSAIDs increase the risk of toxicity due to impairment of renal clearance of pralatrexate thus increasing exposure. Monitor for adverse effects or adjust dose of pralatrexate.
  • Probenecid Probenecid increases the effect/toxicity of indomethacin
  • Propranolol Risk of inhibition of renal prostaglandins
  • Sotalol Risk of inhibition of renal prostaglandins
  • Tamoxifen Indomethacin may reduce clearance rate of Tamoxifen. Monitor for changes in therapeutic/adverse effects of Tamoxifen if Indomethacin is initiated, discontinued or dose changed.
  • Telmisartan Concomitant use of Telmisartan and Indomethacin may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.
  • Timolol Risk of inhibition of renal prostaglandins
  • Tolbutamide Indomethacin, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Tolbutamide, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in Tolbutamide therapeutic and adverse effects if Indomethacin is initiated, discontinued or dose changed.
  • Torasemide The NSAID, indomethacin, may decrease the diuretic and antihypertensive effects of the loop diuretic, torasemide.
  • Trandolapril The NSAID, Indomethacin, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Indomethacin is initiated, discontinued or dose changed.
  • Treprostinil The prostacyclin analogue, Treprostinil, may increase the risk of bleeding when combined with the NSAID, Indomethacin. Monitor for increased bleeding during concomitant thearpy.
  • Triamterene Risk of acute renal impairment with this combination
  • Trimethoprim The strong CYP2C9 inhibitor, Indomethacine, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Indomethacine is initiated, discontinued or dose changed.
  • Voriconazole Indomethacin, a strong CYP2C9 inhibitor, may increase the serum concentration of voriconazole by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of voriconazole if indomethacin is initiated, discontinued or dose changed.
  • Warfarin Indomethacin, a strong CYP2C9 inhibitor, may decrease the metabolism of warfarin. The antiplatelet effect of indomethacin may also increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if indomethacin is initiated, discontinued or dose changed.
Liều Lượng & Cách Dùng : Capsule - Oral - 25 mg
Capsule - Oral - 50 mg
Capsule, extended release - Oral - 75 mg
Injection - Intravenous - 1 mg
Suppository - Rectal - 100 mg
Suppository - Rectal - 50 mg
Suspension - Oral - 25 mg/5 ml
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty : Alphapharm
    Sản phẩm biệt dược : Arthrexin
  • Công ty : Sankyo
    Sản phẩm biệt dược : Elmetacin
  • Công ty : Andromaco
    Sản phẩm biệt dược : Indaflex
  • Công ty : Lundbeck
    Sản phẩm biệt dược : Indocid
  • Công ty : Lundbeck
    Sản phẩm biệt dược : Indocin
  • Công ty : Sandoz
    Sản phẩm biệt dược : Indolar SR
  • Công ty : Greater Pharma
    Sản phẩm biệt dược : Indomed
  • Sản phẩm biệt dược : Indoxen
  • Công ty : GlaxoSmithKline
    Sản phẩm biệt dược : Metindol
  • Công ty : Mikasa Seiyaku
    Sản phẩm biệt dược : Mikametan
  • Công ty : Nu-Pharm
    Sản phẩm biệt dược : Nu-Indo
  • Công ty : Vitória
    Sản phẩm biệt dược : Reumacide
  • Công ty :
    Sản phẩm biệt dược : Tivorbex
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00328
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=3715
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46508291
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C01926
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00141
ChemSpider
http://www.chemspider.com/Chemical-Structure.3584.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=17638
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/42211-101-11
PharmGKB
http://www.pharmgkb.org/drug/PA449982
Wikipedia
http://en.wikipedia.org/wiki/Indomethacin
RxList
http://www.rxlist.com/cgi/generic/indometh.htm
Drugs.com
http://www.drugs.com/cdi/indomethacin.html
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