Peringatan Keamanan

Acute oral LD50 is 2.42 mg/kg in rats and 13 mg/kg in mice.MSDS The oral LD50 of indomethacin in mice and rats (based on 14-day mortality response) was 50 and 12 mg/kg, respectively.^L6778

Symptoms of overdose may be characterized by nausea, vomiting, intense headache, dizziness, mental confusion, disorientation, or lethargy. In addition, there have been reports of paresthesias, numbness, and convulsions. In case of an overdose, the patient should receive symptomatic and supportive treatment with stomach emptying through induced vomiting or gastric lavage.^L6778 The patient should then be closely monitored for any signs of gastrointestinal ulceration and hemorrhage. Antacids may be useful.^L6778

Indomethacin

DB00328

small molecule approved investigational

Deskripsi

Indometacin, or indomethacin, is a non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic, and antipyretic properties. NSAIDs consist of agents that are structurally unrelated; the NSAID chemical classification of indometacin is an indole-acetic acid derivative with the chemical name 1- (p-chlorobenzoyl)25-methoxy-2-methylindole-3-acetic acid.^A177871 The pharmacological effect of indometacin is not fully understood, however, it is thought to be mediated through potent and nonselective inhibition of the enzyme cyclooxygenase (COX), which is the main enzyme responsible for catalyzes the rate-limiting step in prostaglandin and thromboxane biosynthesis via the arachidonic acid (AA) pathway. Indometacin was first discovered in 1963 and it was first approved for use in the U.S. by the Food and Drug Administration in 1965, ^A486 along with other acetic acid derivatives such as diclofenac and sulindac that were also developed during the 1960s.^A177871 Since then, indometacin has been extensively studied in clinical trials as one of the most potent NSAIDs in blocking prostaglandin synthesis and was among the first NSAIDs to be used in the symptomatic treatment of migraine and for headaches that eventually became known as “indomethacin-responsive” headache disorders.^A177871

Most commonly used in rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, acute shoulder pains, and acute gouty arthritis, indometacin is currently available as oral capsules as well as other methods of administration, including rectal and intravenous formulations. Intravenous indometacin is administered to close a hemodynamically significant patent ductus arteriosus, as indicated by clinical evidence, in premature infants.^L10553 Ophthalmic indometacin has been studied and used in the symptomatic treatment of postoperative ocular inflammation and pain and/or complications after cataract surgery. Although deemed effective in reducing ocular inflammation in clinical studies, topical NSAIDs were also associated with a potential reduction in corneal sensitivity accompanied by an increased risk of superficial punctate keratitis and subjective symptoms of discomfort, including pain, burning or pricking, or a tingling sensation after instillation into the cul?de?sac.^A177949

Struktur Molekul 2D

Berat 357.788

Wujud solid

Peta Jejaring Molekuler

Obat Target Gen Interaksi Enzim Transporter Carrier

Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

1. Pendahuluan & Konsep

Fitur visualisasi ini dikembangkan menggunakan pendekatan Graph Theory untuk memetakan hubungan polifarmasi dan molekuler. Entitas (Obat, Target, Gen) direpresentasikan sebagai Simpul (Nodes), sedangkan hubungan biologisnya sebagai Sisi (Edges).

2. Sumber Data (Validasi)

Data Obat: Diekstraksi dari elemen drugbank-id dan name pada skema XML DrugBank.
Target Protein: Diambil dari elemen targets/target yang memuat polipeptida sasaran.
Genetik: Disinkronisasi dari sub-elemen gene-name dan varian snp-effects.
Genetik: Jumlah titik node dibatasi pada maksimal 10 (Slice=10) interaksi untuk menghindari tumpukan data.

3. Algoritma Visualisasi

Tata letak grafik menggunakan algoritma Force-Directed Graph (Barnes-Hut). Model fisika ini menerapkan gaya tolak-menolak antar simpul (Gravitasi: -3000) agar tidak tumpang tindih, serta gaya pegas (Spring: 0.04) pada garis penghubung untuk fleksibilitas interaksi.

4. Legenda Visual

Obat Utama (Pusat Analisis)

Target Protein (Mekanisme)

Gen (Faktor Genetik)

Metode ini mendukung analisis Precision Medicine dan evaluasi risiko Drug-Drug Interaction (DDI).

Profil Farmakokinetik

Waktu Paruh (Half-Life) Indometacin disposition from the plasma is reported to be biphasic, with a half-life of 1 hour during the initial phase and 2.6–11.2 hours during the second phase.[A177949] Interindividual and intraindividual variations are possible due to the extensive and sporadic nature of the enterohepatic recycling and biliary discharge of the drug.[A177874,A177949] The mean half-life of oral indomethacin is estimated to be about 4.5 hours.[L6778] The disposition of intravenous indometacin in preterm neonates was shown to vary across premature infants. In neonates older than 7 days, the mean plasma half-life of intravenous indometacin was approximately 20 hours, ranging from 15 hours in infants weighing more than 1000 g and 21 hours in infants weighing less than 1000 g.[L10553]

Volume Distribusi The volume of distribution ranged from 0.34 to 1.57 L/kg following oral, intravenous, or rectal administration of single and multiple doses of indometacin in healthy individuals.[A177964] Indometacin is distributed into the synovial fluid [A177874] and is extensively bound to tissues [A177949]. It has been detected in human breast milk [A177874] and placenta.[L6778] Although indometacin has been shown to cross the blood-brain barrier (BBB)[L6778], its extensive plasma protein binding allows only the small fraction of free or unbound indometacin to diffuse across the BBB.[A177949]

Klirens (Clearance) In a clinical pharmacokinetic study, the plasma clearance of indometacin was reported to range from 1 to 2.5 mL/kg/min following oral administration.[A177874]

Absorpsi

Indometacin displays a linear pharmacokinetics profile where the plasma concentrations and area under the curve (AUC) are dose-proportional, whereas half-life (T1/2) and plasma and renal clearance are dose-dependent.^A177871 Indometacin is readily and rapidly absorbed from the gastrointestinal tract. The bioavailability is virtually 100% following oral administration ^A177871 and about 90% of the dose is absorbed within 4 hours.^L6778 The bioavailability is about 80-90% following rectal administration.^A177901 The peak plasma concentrations following a single oral dose were achieved between 0.9 ± 0.4 and 1.5 ± 0.8 hours in a fasting state.^A177901 Despite large intersubject variation as well using the same preparation, peak plasma concentrations are dose-proportional and averaged 1.54 ± 0.76 ?g/mL, 2.65 ± 1.03 ?g/mL, and 4.92 ± 1.88 ?g/mL following 25 mg, 50 mg, and 75 mg single doses in fasting subjects, respectively.^A177901 With a typical therapeutic regimen of 25 or 50 mg t.i.d., the steady-state plasma concentrations of indomethacin are an average 1.4 times those following the first dose.^L6778

Metabolisme

Indometacin undergoes hepatic metabolism involving glucuronidation, O-desmethylation, and N-deacylation.^A177949 O-desmethyl-indomethacin, N-deschlorobenzoyl-indomethacin, and O-desmethyl-N-deschlorobenzoyl-indomethacin metabolites and their glucuronides are primarily inactive and have no pharmacological activity.A177949,L6778 Unconjugated metabolites are also detected in the plasma.^L6778 Its high bioavailability indicates that indometacin is unlikely to be subject to the first-pass metabolism.^A177949

Rute Eliminasi

Indometacin is eliminated via renal excretion, metabolism, and biliary excretion. It is also subject to enter the enterohepatic circulation through excretion of its glucuronide metabolites into bile followed by resorption of indometacin after hydrolysis ^A177949. The extent of involvement in the enterohepatic circulation ranges from 27 to 115%.^A177949 About 60 percent of an oral dosage is recovered in urine as drug and metabolites (26 percent as indomethacin and its glucuronide), and 33 percent in the feces (1.5 percent as indomethacin).^L6778

Interaksi Makanan

2 Data

1. Avoid alcohol. Ingestion of alcohol can increase the risk of GI bleeding.
2. Take with or without food. Food has no effect on drug absorption. However, food may decrease the extent of gastrointestinal irritation caused by indomethacin.

Interaksi Obat

2010 Data

Denosumab	The risk or severity of adverse effects can be increased when Denosumab is combined with Indomethacin.
Peginterferon alfa-2a	The risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Indomethacin.
Interferon alfa-n1	The risk or severity of adverse effects can be increased when Interferon alfa-n1 is combined with Indomethacin.
Interferon alfa-n3	The risk or severity of adverse effects can be increased when Interferon alfa-n3 is combined with Indomethacin.
Peginterferon alfa-2b	The risk or severity of adverse effects can be increased when Peginterferon alfa-2b is combined with Indomethacin.
Interferon gamma-1b	The risk or severity of adverse effects can be increased when Interferon gamma-1b is combined with Indomethacin.
Interferon alfa-2a	The risk or severity of adverse effects can be increased when Interferon alfa-2a is combined with Indomethacin.
Aldesleukin	The risk or severity of adverse effects can be increased when Aldesleukin is combined with Indomethacin.
Gemtuzumab ozogamicin	The risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Indomethacin.
Pegaspargase	The risk or severity of adverse effects can be increased when Pegaspargase is combined with Indomethacin.
Interferon beta-1b	The risk or severity of adverse effects can be increased when Interferon beta-1b is combined with Indomethacin.
Interferon alfacon-1	The risk or severity of adverse effects can be increased when Interferon alfacon-1 is combined with Indomethacin.
Rituximab	The risk or severity of adverse effects can be increased when Rituximab is combined with Indomethacin.
Basiliximab	The risk or severity of adverse effects can be increased when Basiliximab is combined with Indomethacin.
Muromonab	The risk or severity of adverse effects can be increased when Muromonab is combined with Indomethacin.
Ibritumomab tiuxetan	The risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with Indomethacin.
Tositumomab	The risk or severity of adverse effects can be increased when Tositumomab is combined with Indomethacin.
Alemtuzumab	The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Indomethacin.
Alefacept	The risk or severity of adverse effects can be increased when Alefacept is combined with Indomethacin.
Efalizumab	The risk or severity of adverse effects can be increased when Efalizumab is combined with Indomethacin.
Antithymocyte immunoglobulin (rabbit)	The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Indomethacin.
Interferon alfa-2b	The risk or severity of adverse effects can be increased when Interferon alfa-2b is combined with Indomethacin.
Daclizumab	The risk or severity of adverse effects can be increased when Daclizumab is combined with Indomethacin.
Phenylalanine	The risk or severity of adverse effects can be increased when Phenylalanine is combined with Indomethacin.
Bortezomib	The risk or severity of adverse effects can be increased when Bortezomib is combined with Indomethacin.
Cladribine	Indomethacin may increase the immunosuppressive activities of Cladribine.
Carmustine	The risk or severity of adverse effects can be increased when Carmustine is combined with Indomethacin.
Amsacrine	The risk or severity of adverse effects can be increased when Amsacrine is combined with Indomethacin.
Bleomycin	The risk or severity of adverse effects can be increased when Bleomycin is combined with Indomethacin.
Chlorambucil	The risk or severity of adverse effects can be increased when Chlorambucil is combined with Indomethacin.
Raltitrexed	The risk or severity of adverse effects can be increased when Raltitrexed is combined with Indomethacin.
Mitomycin	The risk or severity of adverse effects can be increased when Mitomycin is combined with Indomethacin.
Bexarotene	The risk or severity of adverse effects can be increased when Bexarotene is combined with Indomethacin.
Vindesine	The risk or severity of adverse effects can be increased when Vindesine is combined with Indomethacin.
Tioguanine	The risk or severity of adverse effects can be increased when Indomethacin is combined with Tioguanine.
Vinorelbine	The risk or severity of adverse effects can be increased when Indomethacin is combined with Vinorelbine.
Dexrazoxane	The risk or severity of adverse effects can be increased when Indomethacin is combined with Dexrazoxane.
Streptozocin	The risk or severity of adverse effects can be increased when Indomethacin is combined with Streptozocin.
Trifluridine	The risk or severity of adverse effects can be increased when Indomethacin is combined with Trifluridine.
Gemcitabine	The risk or severity of adverse effects can be increased when Indomethacin is combined with Gemcitabine.
Teniposide	The risk or severity of adverse effects can be increased when Indomethacin is combined with Teniposide.
Epirubicin	The risk or severity of adverse effects can be increased when Indomethacin is combined with Epirubicin.
Chloramphenicol	The risk or severity of adverse effects can be increased when Indomethacin is combined with Chloramphenicol.
Lenalidomide	The risk or severity of adverse effects can be increased when Indomethacin is combined with Lenalidomide.
Altretamine	The risk or severity of adverse effects can be increased when Indomethacin is combined with Altretamine.
Oxaliplatin	The risk or severity of nephrotoxicity can be increased when Oxaliplatin is combined with Indomethacin.
Fluorouracil	The risk or severity of adverse effects can be increased when Indomethacin is combined with Fluorouracil.
Propylthiouracil	The risk or severity of adverse effects can be increased when Indomethacin is combined with Propylthiouracil.
Pentostatin	The risk or severity of adverse effects can be increased when Indomethacin is combined with Pentostatin.
Vinblastine	The risk or severity of adverse effects can be increased when Indomethacin is combined with Vinblastine.
Linezolid	The risk or severity of adverse effects can be increased when Indomethacin is combined with Linezolid.
Imatinib	The risk or severity of adverse effects can be increased when Indomethacin is combined with Imatinib.
Clofarabine	The risk or severity of adverse effects can be increased when Indomethacin is combined with Clofarabine.
Mycophenolate mofetil	The risk or severity of adverse effects can be increased when Indomethacin is combined with Mycophenolate mofetil.
Daunorubicin	The risk or severity of adverse effects can be increased when Indomethacin is combined with Daunorubicin.
Tretinoin	The risk or severity of elevated intracranial pressure can be increased when Indomethacin is combined with Tretinoin.
Methimazole	The risk or severity of adverse effects can be increased when Indomethacin is combined with Methimazole.
Dacarbazine	The risk or severity of adverse effects can be increased when Indomethacin is combined with Dacarbazine.
Temozolomide	The risk or severity of adverse effects can be increased when Indomethacin is combined with Temozolomide.
Penicillamine	The risk or severity of adverse effects can be increased when Indomethacin is combined with Penicillamine.
Mechlorethamine	The risk or severity of adverse effects can be increased when Indomethacin is combined with Mechlorethamine.
Azacitidine	The risk or severity of adverse effects can be increased when Indomethacin is combined with Azacitidine.
Carboplatin	The risk or severity of adverse effects can be increased when Indomethacin is combined with Carboplatin.
Dactinomycin	The risk or severity of adverse effects can be increased when Indomethacin is combined with Dactinomycin.
Cytarabine	The risk or severity of adverse effects can be increased when Indomethacin is combined with Cytarabine.
Azathioprine	The risk or severity of adverse effects can be increased when Indomethacin is combined with Azathioprine.
Hydroxyurea	The risk or severity of adverse effects can be increased when Indomethacin is combined with Hydroxyurea.
Busulfan	The risk or severity of adverse effects can be increased when Indomethacin is combined with Busulfan.
Mercaptopurine	The risk or severity of adverse effects can be increased when Indomethacin is combined with Mercaptopurine.
Thalidomide	The risk or severity of adverse effects can be increased when Indomethacin is combined with Thalidomide.
Melphalan	The risk or severity of adverse effects can be increased when Indomethacin is combined with Melphalan.
Fludarabine	The risk or severity of adverse effects can be increased when Indomethacin is combined with Fludarabine.
Flucytosine	The risk or severity of adverse effects can be increased when Indomethacin is combined with Flucytosine.
Procarbazine	The risk or severity of adverse effects can be increased when Indomethacin is combined with Procarbazine.
Arsenic trioxide	The risk or severity of adverse effects can be increased when Indomethacin is combined with Arsenic trioxide.
Idarubicin	The risk or severity of adverse effects can be increased when Indomethacin is combined with Idarubicin.
Ifosfamide	The risk or severity of adverse effects can be increased when Indomethacin is combined with Ifosfamide.
Estramustine	The risk or severity of adverse effects can be increased when Indomethacin is combined with Estramustine.
Mitoxantrone	The risk or severity of adverse effects can be increased when Indomethacin is combined with Mitoxantrone.
Lomustine	The risk or severity of adverse effects can be increased when Indomethacin is combined with Lomustine.
Docetaxel	The risk or severity of adverse effects can be increased when Indomethacin is combined with Docetaxel.
Dasatinib	The risk or severity of adverse effects can be increased when Indomethacin is combined with Dasatinib.
Eculizumab	The risk or severity of adverse effects can be increased when Indomethacin is combined with Eculizumab.
Decitabine	The risk or severity of adverse effects can be increased when Indomethacin is combined with Decitabine.
Sunitinib	The risk or severity of adverse effects can be increased when Indomethacin is combined with Sunitinib.
Nelarabine	The risk or severity of adverse effects can be increased when Indomethacin is combined with Nelarabine.
Stepronin	The risk or severity of adverse effects can be increased when Indomethacin is combined with Stepronin.
Hydroxychloroquine	The risk or severity of adverse effects can be increased when Indomethacin is combined with Hydroxychloroquine.
Castanospermine	The risk or severity of adverse effects can be increased when Indomethacin is combined with Castanospermine.
Vorinostat	The risk or severity of adverse effects can be increased when Indomethacin is combined with Vorinostat.
2-Methoxyethanol	The risk or severity of adverse effects can be increased when Indomethacin is combined with 2-Methoxyethanol.
Brequinar	The risk or severity of adverse effects can be increased when Indomethacin is combined with Brequinar.
Thiotepa	The risk or severity of adverse effects can be increased when Indomethacin is combined with Thiotepa.
Ixabepilone	The risk or severity of adverse effects can be increased when Indomethacin is combined with Ixabepilone.
Nilotinib	The risk or severity of adverse effects can be increased when Indomethacin is combined with Nilotinib.
Pirfenidone	The risk or severity of adverse effects can be increased when Indomethacin is combined with Pirfenidone.
Interferon alfa	The risk or severity of adverse effects can be increased when Indomethacin is combined with Interferon alfa.
Glatiramer	The risk or severity of adverse effects can be increased when Indomethacin is combined with Glatiramer.
Briakinumab	The risk or severity of adverse effects can be increased when Indomethacin is combined with Briakinumab.
Human interferon omega-1	The risk or severity of adverse effects can be increased when Indomethacin is combined with Human interferon omega-1.

Target Protein

Prostaglandin G/H synthase 2 PTGS2

Phospholipase A2, membrane associated PLA2G2A

Human Cyclooxygenases PTGS1

Prostaglandin G/H synthase 1 PTGS1

Prostaglandin reductase 2 PTGR2

Peroxisome proliferator-activated receptor gamma PPARG

Lactoylglutathione lyase GLO1

Prostaglandin D2 receptor 2 PTGDR2

Peroxisome proliferator-activated receptor alpha PPARA

Aldo-keto reductase family 1 member C3 AKR1C3

Interferon-induced, double-stranded RNA-activated protein kinase EIF2AK2

Referensi & Sumber

Synthesis reference: Hubertus L. Regtop, John R. Biffin, "Preparation of divalent metal salts of indomethacin." U.S. Patent US5310936, issued November, 1917.

Artikel (PubMed)

PMID: 26865183
Lucas S: The Pharmacology of Indomethacin. Headache. 2016 Feb;56(2):436-46. doi: 10.1111/head.12769. Epub 2016 Feb 11.
PMID: 7249487
Helleberg L: Clinical Pharmacokinetics of indomethacin. Clin Pharmacokinet. 1981 Jul-Aug;6(4):245-58. doi: 10.2165/00003088-198106040-00001.
PMID: 25141247
Nalamachu S, Wortmann R: Role of indomethacin in acute pain and inflammation management: a review of the literature. Postgrad Med. 2014 Jul;126(4):92-7. doi: 10.3810/pgm.2014.07.2787.
PMID: 23754139
Pacifici GM: Clinical pharmacology of indomethacin in preterm infants: implications in patent ductus arteriosus closure. Paediatr Drugs. 2013 Oct;15(5):363-76. doi: 10.1007/s40272-013-0031-7.
PMID: 4090993
Jensen KM, Grenabo L: Bioavailability of indomethacin after intramuscular injection and rectal administration of solution and suppositories. Acta Pharmacol Toxicol (Copenh). 1985 Nov;57(5):322-7.
PMID: 22970738
Weber M, Kodjikian L, Kruse FE, Zagorski Z, Allaire CM: Efficacy and safety of indomethacin 0.1% eye drops compared with ketorolac 0.5% eye drops in the management of ocular inflammation after cataract surgery. Acta Ophthalmol. 2013 Feb;91(1):e15-21. doi: 10.1111/j.1755-3768.2012.02520.x. Epub 2012 Sep 12.
PMID: 1100305
Alvan G, Orme M, Bertilsson L, Ekstrand R, Palmer L: Pharmacokinetics of indomethacin. Clin Pharmacol Ther. 1975 Sep;18(3):364-73.
PMID: 21508345
Ricciotti E, FitzGerald GA: Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol. 2011 May;31(5):986-1000. doi: 10.1161/ATVBAHA.110.207449.

Menampilkan 8 dari 12 artikel.

Link

Contoh Produk & Brand

Produk: 287 • International brands: 12

Produk

Apo-indomethacin

Capsule • 25 mg • Oral • Canada • Generic • Approved
Apo-indomethacin

Capsule • 50 mg • Oral • Canada • Generic • Approved
Auro-indomethacin

Capsule • 50 mg • Oral • Canada • Generic • Approved
Ftp-indomethacin

Capsule • 25 mg / cap • Oral • Canada • Generic • Approved
Ftp-indomethacin

Capsule • 50 mg / cap • Oral • Canada • Generic • Approved
Indocid Cap 25mg

Capsule • 25 mg / cap • Oral • Canada • Approved
Indocid Cap 50mg

Capsule • 50 mg / cap • Oral • Canada • Approved
Indocid SR 75mg

Capsule, extended release • 75 mg / cap • Oral • Canada • Approved

Menampilkan 8 dari 287 produk.

International Brands

Aconip — Teika Pharmaceutical Co.,Ltd.
Arthrexin — Alphapharm
Elmetacin — Sankyo
Indaflex — Andromaco
Indocid — Lundbeck
Indolar SR — Sandoz
Indomed — Greater Pharma
Indoxen — Quality Pharmaceutical
Metindol — GlaxoSmithKline
Mikametan — Mikasa Seiyaku

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.