Peringatan Keamanan

No information is available regarding the LD₅₀ or overdose of linaclotide. Single linaclotide doses of 2897 mcg were administered to 22 healthy subjects; the safety profile in these subjects was consistent with that in the overall linaclotide-treated population, with diarrhea being the most commonly reported adverse reaction.^L47211

Linaclotide

DB08890

small molecule approved

Deskripsi

Linaclotide is a synthetic 14-amino acid cyclic peptide ^A260271 and first-in-class guanylate cyclase-C (G-CC) agonist.A260271, L47211 Linaclotide is structurally related to human guanylin and uroguanylin, paracrine peptide hormones that are endogenous activators of GC-C.^A260276 It is also a homolog of a heat-stable enterotoxin derived from Escherichia coli, the first natural ligand that activates GC-C.^A260286

Linaclotide is used for the treatment of various types of constipation, including irritable bowel syndrome with constipation. Linaclotide was first approved by the FDA on August 30, 2012.^A260271 It gained EMA and Health Canada approval on November 26, 2012 ^L47216 and December 3, 2013,^L47221 respectively. Linaclotide works to improve the symptoms of constipation and gastrointestinal symptoms of conditions involving constipation.^A260286

Struktur Molekul 2D

Berat 1526.736

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) There is no available information regarding the half-life as the concentrations of linaclotide and its active metabolite in plasma are below the limit of quantitation.[L47211]

Volume Distribusi Given that linaclotide plasma concentrations following recommended oral doses are not measurable, linaclotide is not expected to be distributed to tissues to any clinically relevant extent.[L47211]

Klirens (Clearance) No information is available.

Absorpsi

Linaclotide is minimally absorbed with negligible systemic availability following oral administration; however, systemic exposure is not of importance for the maximal effects of linaclotide, as the ligand-binding domain of the GC-C target is located on the luminal surface of intestinal epithelial cells.^A7468 There is no available information regarding the area under the curve (AUC) and peak plasma concentrations (C_max) as the concentrations of linaclotide and its active metabolite in plasma are below the limit of quantitation.^L47211

Metabolisme

Linaclotide is metabolized in the small intestine, where it loses its C-terminal tyrosine moiety to form a principal active metabolite, MM-419447.A7468, A260281 The disulfide bonds of linaclotide and MM-419447 are reduced in the intestinal lumen, followed by proteolysis and degradation to form smaller peptides and naturally occurring amino acids A7468, L47211 which are absorbed through the intestine.^A260286 In rats in vitro, linaclotide was resistant to enzymatic hydrolysis by pepsin, trypsin, aminopeptidase or chymotrypsin.^A260286

Rute Eliminasi

Following once-daily administration of 290 mcg linaclotide for seven days, the average active peptide recovery in the stool samples of fed and fasted healthy subjects was 3% and 5%, respectively. The recovered active peptide constituted the active metabolite.^L47211

Interaksi Makanan

1 Data

1. Take on an empty stomach. Take linaclotide at least 30 minutes prior to a meal, at approximately the same time each day. A high fat meal may cause looser stools and a higher stool frequency.

Interaksi Obat

400 Data

Tramadol	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Tramadol.
Trospium	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Trospium.
Oxyphenonium	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Oxyphenonium.
Benzatropine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Benzatropine.
Ziprasidone	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Ziprasidone.
Disopyramide	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Disopyramide.
Amitriptyline	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Amitriptyline.
Ipratropium	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Ipratropium.
Olanzapine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Olanzapine.
Metixene	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Metixene.
Terfenadine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Terfenadine.
Buclizine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Buclizine.
Clozapine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Clozapine.
Doxylamine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Doxylamine.
Trihexyphenidyl	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Trihexyphenidyl.
Oxyphencyclimine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Oxyphencyclimine.
Procyclidine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Procyclidine.
Profenamine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Profenamine.
Promazine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Promazine.
Hyoscyamine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Hyoscyamine.
Cyproheptadine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Cyproheptadine.
Imipramine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Imipramine.
Methscopolamine bromide	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Methscopolamine bromide.
Chlorpromazine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Chlorpromazine.
Gallamine triethiodide	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Gallamine triethiodide.
Darifenacin	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Darifenacin.
Tridihexethyl	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Tridihexethyl.
Triflupromazine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Triflupromazine.
Anisotropine methylbromide	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Anisotropine methylbromide.
Nortriptyline	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Nortriptyline.
Amoxapine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Amoxapine.
Atropine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Atropine.
Nicardipine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Nicardipine.
Pirenzepine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Pirenzepine.
Paroxetine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Paroxetine.
Homatropine methylbromide	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Homatropine methylbromide.
Rocuronium	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Rocuronium.
Scopolamine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Scopolamine.
Benzquinamide	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Benzquinamide.
Clidinium	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Clidinium.
Propiomazine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Propiomazine.
Propantheline	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Propantheline.
Dicyclomine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Dicyclomine.
Biperiden	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Biperiden.
Brompheniramine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Brompheniramine.
Flupentixol	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Flupentixol.
Cocaine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Cocaine.
Quinidine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Quinidine.
Maprotiline	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Maprotiline.
Methantheline	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Methantheline.
Cycrimine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Cycrimine.
Glycopyrronium	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Glycopyrronium.
Tolterodine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Tolterodine.
Oxybutynin	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Oxybutynin.
Promethazine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Promethazine.
Diphenhydramine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Diphenhydramine.
Doxacurium	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Doxacurium.
Doxepin	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Doxepin.
Flavoxate	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Flavoxate.
Desipramine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Desipramine.
Orphenadrine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Orphenadrine.
Escitalopram	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Escitalopram.
Quetiapine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Quetiapine.
Mivacurium	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Mivacurium.
Diphenidol	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Diphenidol.
Aripiprazole	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Aripiprazole.
Chlorprothixene	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Chlorprothixene.
Metocurine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Metocurine.
Pancuronium	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Pancuronium.
Pipecuronium	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Pipecuronium.
Methotrimeprazine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Methotrimeprazine.
Tiotropium	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Tiotropium.
Solifenacin	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Solifenacin.
Isopropamide	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Isopropamide.
Rapacuronium	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Rapacuronium.
Mepenzolate	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Mepenzolate.
Pizotifen	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Pizotifen.
Fesoterodine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Fesoterodine.
Hexocyclium	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Hexocyclium.
Dimetindene	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Dimetindene.
Aclidinium	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Aclidinium.
Dexetimide	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Dexetimide.
Benactyzine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Benactyzine.
Umeclidinium	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Umeclidinium.
Trimebutine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Trimebutine.
Dosulepin	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Dosulepin.
Imidafenacin	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Imidafenacin.
Butylscopolamine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Butylscopolamine.
Thonzylamine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Thonzylamine.
Methscopolamine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Methscopolamine.
Revefenacin	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Revefenacin.
Oxitropium	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Oxitropium.
Propiverine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Propiverine.
Batefenterol	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Batefenterol.
Mebeverine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Mebeverine.
Tropatepine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Tropatepine.
Prifinium	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Prifinium.
Piperidolate	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Piperidolate.
Benzilone	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Benzilone.
Difemerine	The therapeutic efficacy of Linaclotide can be decreased when used in combination with Difemerine.

Target Protein

Guanylyl cyclase C GUCY2C

Referensi & Sumber

Artikel (PubMed)

PMID: 23090647
Busby RW, Kessler MM, Bartolini WP, Bryant AP, Hannig G, Higgins CS, Solinga RM, Tobin JV, Wakefield JD, Kurtz CB, Currie MG: Pharmacologic properties, metabolism, and disposition of linaclotide, a novel therapeutic peptide approved for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation. J Pharmacol Exp Ther. 2013 Jan;344(1):196-206. doi: 10.1124/jpet.112.199430. Epub 2012 Oct 22.
PMID: 35201736
Kalola UK, Chowdhury YS: Linaclotide. .
PMID: 24433216
Layer P, Stanghellini V: Review article: Linaclotide for the management of irritable bowel syndrome with constipation. Aliment Pharmacol Ther. 2014 Feb;39(4):371-84. doi: 10.1111/apt.12604. Epub 2014 Jan 16.
PMID: 23083112
McWilliams V, Whiteside G, McKeage K: Linaclotide: first global approval. Drugs. 2012 Nov 12;72(16):2167-75. doi: 10.2165/11470590-000000000-00000.
PMID: 24917937
Corsetti M, Tack J: Linaclotide: A new drug for the treatment of chronic constipation and irritable bowel syndrome with constipation. United European Gastroenterol J. 2013 Feb;1(1):7-20. doi: 10.1177/2050640612474446.

Link

Contoh Produk & Brand

Produk: 13 • International brands: 0

Produk

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Capsule • 290 mcg • Oral • EU • Approved
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Capsule • 290 mcg • Oral • EU • Approved
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Menampilkan 8 dari 13 produk.

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.