Peringatan Keamanan

Oral, mouse: LD₅₀ = 2600 mg/kg

Tolbutamide

DB01124

small molecule approved investigational

Deskripsi

Tolbutamide is an oral antihyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus (NIDDM). It is structurally similar to acetohexamide, chlorpropamide and tolazamide and belongs to the sulfonylurea class of insulin secretagogues, which act by stimulating ? cells of the pancreas to release insulin. Sulfonylureas increase both basal insulin secretion and meal-stimulated insulin release. Medications in this class differ in their dose, rate of absorption, duration of action, route of elimination and binding site on their target pancreatic ? cell receptor. Sulfonylureas also increase peripheral glucose utilization, decrease hepatic gluconeogenesis and may increase the number and sensitivity of insulin receptors. Sulfonylureas are associated with weight gain, though less so than insulin. Due to their mechanism of action, sulfonylureas may cause hypoglycemia and require consistent food intake to decrease this risk. The risk of hypoglycemia is increased in elderly, debilitated and malnourished individuals. Tolbutamide appears to be metabolized in the liver. Tolbutamide and its metabolites are excreted in urine (75-85%) and feces.

Struktur Molekul 2D

Berat 270.348

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) Approximately 7 hours with interindividual variations ranging from 4-25 hours. Tolbutamide has the shortest duration of action, 6-12 hours, of the antidiabetic sulfonylureas.

Volume Distribusi -

Klirens (Clearance) -

Absorpsi

Readily absorbed following oral administration. Tolbutamide is detectable in plasma 30-60 minutes following oral administration of a single dose with peak plasma concentrations occurring within 3-5 hours. Absorption is unaltered if taken with food but is increased with high pH.

Metabolisme

Metabolized in the liver principally via oxidation of the p-methyl group producing the carboxyl metabolite, 1-butyl-3-p-carboxyphenylsulfonylurea. May also be metabolized to hydroxytolbutamide. Tolbutamide does not undergo acetylation like antibacterial sulfonamides as it does not have a p-amino group.

Rute Eliminasi

Unchanged drug and metabolites are eliminated in the urine and feces. Approximately 75-85% of a single orally administered dose is excreted in the urine principally as the 1-butyl-3-p-carboxyphenylsulfonylurea within 24 hours.

Farmakogenomik

1 Varian

CYP2C9 (rs1057910)

Patients with this genotype have reduced metabolism of tolbutamide.

Interaksi Makanan

2 Data

1. Avoid alcohol. Ingesting alcohol may precipitate a disulfiram-like reaction (flushing, nausea), or hypoglycemia.
2. Take with or without food.

Interaksi Obat

1577 Data

Pegvisomant	The risk or severity of hypoglycemia can be increased when Pegvisomant is combined with Tolbutamide.
Carbocisteine	The risk or severity of adverse effects can be increased when Tolbutamide is combined with Carbocisteine.
Chloramphenicol	The metabolism of Tolbutamide can be decreased when combined with Chloramphenicol.
Cimetidine	The serum concentration of Tolbutamide can be increased when it is combined with Cimetidine.
Fluconazole	The serum concentration of Tolbutamide can be increased when it is combined with Fluconazole.
Metreleptin	Metreleptin may increase the hypoglycemic activities of Tolbutamide.
Probenecid	The protein binding of Tolbutamide can be decreased when combined with Probenecid.
Ranitidine	The serum concentration of Tolbutamide can be increased when it is combined with Ranitidine.
Voriconazole	The serum concentration of Tolbutamide can be increased when it is combined with Voriconazole.
Mifepristone	The serum concentration of Tolbutamide can be increased when it is combined with Mifepristone.
Clarithromycin	The serum concentration of Tolbutamide can be increased when it is combined with Clarithromycin.
Leflunomide	The serum concentration of Tolbutamide can be increased when it is combined with Leflunomide.
Teriflunomide	The serum concentration of Tolbutamide can be increased when it is combined with Teriflunomide.
Lipoic acid	The risk or severity of hypoglycemia can be increased when Lipoic acid is combined with Tolbutamide.
Rifampin	The serum concentration of Tolbutamide can be decreased when it is combined with Rifampicin.
Moxifloxacin	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Moxifloxacin.
Grepafloxacin	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Grepafloxacin.
Enoxacin	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Enoxacin.
Pefloxacin	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Pefloxacin.
Ciprofloxacin	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Ciprofloxacin.
Trovafloxacin	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Trovafloxacin.
Nalidixic acid	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Nalidixic acid.
Rosoxacin	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Rosoxacin.
Cinoxacin	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Cinoxacin.
Lomefloxacin	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Lomefloxacin.
Gatifloxacin	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Gatifloxacin.
Norfloxacin	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Norfloxacin.
Levofloxacin	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Levofloxacin.
Gemifloxacin	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Gemifloxacin.
Ofloxacin	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Ofloxacin.
Sparfloxacin	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Sparfloxacin.
Temafloxacin	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Temafloxacin.
Fleroxacin	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Fleroxacin.
Technetium Tc-99m ciprofloxacin	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Technetium Tc-99m ciprofloxacin.
Garenoxacin	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Garenoxacin.
Nemonoxacin	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Nemonoxacin.
Flumequine	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Flumequine.
Enrofloxacin	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Enrofloxacin.
Orbifloxacin	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Orbifloxacin.
Sarafloxacin	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Sarafloxacin.
Difloxacin	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Difloxacin.
Pazufloxacin	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Pazufloxacin.
Prulifloxacin	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Prulifloxacin.
Delafloxacin	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Delafloxacin.
Sitafloxacin	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Sitafloxacin.
Oxolinic acid	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Oxolinic acid.
Rufloxacin	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Rufloxacin.
Pipemidic acid	The therapeutic efficacy of Tolbutamide can be increased when used in combination with Pipemidic acid.
Methyclothiazide	The therapeutic efficacy of Tolbutamide can be decreased when used in combination with Methyclothiazide.
Chlorthalidone	The therapeutic efficacy of Tolbutamide can be decreased when used in combination with Chlorthalidone.
Bendroflumethiazide	The therapeutic efficacy of Tolbutamide can be decreased when used in combination with Bendroflumethiazide.
Metolazone	The therapeutic efficacy of Tolbutamide can be decreased when used in combination with Metolazone.
Benzthiazide	The therapeutic efficacy of Tolbutamide can be decreased when used in combination with Benzthiazide.
Hydroflumethiazide	The therapeutic efficacy of Tolbutamide can be decreased when used in combination with Hydroflumethiazide.
Indapamide	The therapeutic efficacy of Tolbutamide can be decreased when used in combination with Indapamide.
Chlorothiazide	The therapeutic efficacy of Tolbutamide can be decreased when used in combination with Chlorothiazide.
Hydrochlorothiazide	The therapeutic efficacy of Tolbutamide can be decreased when used in combination with Hydrochlorothiazide.
Trichlormethiazide	The therapeutic efficacy of Tolbutamide can be decreased when used in combination with Trichlormethiazide.
Polythiazide	The therapeutic efficacy of Tolbutamide can be decreased when used in combination with Polythiazide.
Quinethazone	The therapeutic efficacy of Tolbutamide can be decreased when used in combination with Quinethazone.
Cyclopenthiazide	The therapeutic efficacy of Tolbutamide can be decreased when used in combination with Cyclopenthiazide.
Epitizide	The therapeutic efficacy of Tolbutamide can be decreased when used in combination with Epitizide.
Esmolol	Esmolol may increase the hypoglycemic activities of Tolbutamide.
Landiolol	Landiolol may increase the hypoglycemic activities of Tolbutamide.
Ethanol	The risk or severity of adverse effects can be increased when Tolbutamide is combined with Ethanol.
Protriptyline	Protriptyline may decrease the hypoglycemic activities of Tolbutamide.
Nortriptyline	Nortriptyline may decrease the hypoglycemic activities of Tolbutamide.
Amoxapine	Amoxapine may decrease the hypoglycemic activities of Tolbutamide.
Amineptine	Amineptine may decrease the hypoglycemic activities of Tolbutamide.
Butriptyline	Butriptyline may decrease the hypoglycemic activities of Tolbutamide.
Dosulepin	Dosulepin may decrease the hypoglycemic activities of Tolbutamide.
Tianeptine	Tianeptine may decrease the hypoglycemic activities of Tolbutamide.
Oxaprotiline	Oxaprotiline may decrease the hypoglycemic activities of Tolbutamide.
Opipramol	Opipramol may decrease the hypoglycemic activities of Tolbutamide.
Amitriptylinoxide	Amitriptylinoxide may decrease the hypoglycemic activities of Tolbutamide.
Dibenzepin	Dibenzepin may decrease the hypoglycemic activities of Tolbutamide.
Quinupramine	Quinupramine may decrease the hypoglycemic activities of Tolbutamide.
Melitracen	Melitracen may decrease the hypoglycemic activities of Tolbutamide.
Lofepramine	Lofepramine may decrease the hypoglycemic activities of Tolbutamide.
Iprindole	Iprindole may decrease the hypoglycemic activities of Tolbutamide.
Imipramine oxide	Imipramine oxide may decrease the hypoglycemic activities of Tolbutamide.
Doxepin	Doxepin may decrease the hypoglycemic activities of Tolbutamide.
Imipramine	Imipramine may decrease the hypoglycemic activities of Tolbutamide.
Desipramine	Desipramine may decrease the hypoglycemic activities of Tolbutamide.
Clomipramine	Clomipramine may decrease the hypoglycemic activities of Tolbutamide.
Dimetacrine	Dimetacrine may decrease the hypoglycemic activities of Tolbutamide.
Clofibrate	The risk or severity of hypoglycemia can be increased when Clofibrate is combined with Tolbutamide.
Fenofibrate	The risk or severity of hypoglycemia can be increased when Fenofibrate is combined with Tolbutamide.
Bezafibrate	The risk or severity of hypoglycemia can be increased when Bezafibrate is combined with Tolbutamide.
Etofibrate	The risk or severity of hypoglycemia can be increased when Etofibrate is combined with Tolbutamide.
Ciprofibrate	The risk or severity of hypoglycemia can be increased when Ciprofibrate is combined with Tolbutamide.
Simfibrate	The risk or severity of hypoglycemia can be increased when Simfibrate is combined with Tolbutamide.
Ronifibrate	The risk or severity of hypoglycemia can be increased when Ronifibrate is combined with Tolbutamide.
Aluminium clofibrate	The risk or severity of hypoglycemia can be increased when Aluminium clofibrate is combined with Tolbutamide.
Clofibride	The risk or severity of hypoglycemia can be increased when Clofibride is combined with Tolbutamide.
Fenofibric acid	The risk or severity of hypoglycemia can be increased when Fenofibric acid is combined with Tolbutamide.
Miconazole	The serum concentration of Tolbutamide can be increased when it is combined with Miconazole.
Phenindione	Tolbutamide may increase the anticoagulant activities of Phenindione.
Coumarin	Tolbutamide may increase the anticoagulant activities of Coumarin.
Clorindione	Tolbutamide may increase the anticoagulant activities of Clorindione.

Target Protein

ATP-binding cassette sub-family C member 9 ABCC9

ATP-binding cassette sub-family C member 8 ABCC8

ATP-sensitive inward rectifier potassium channel 1 KCNJ1

Referensi & Sumber

Synthesis reference: Yan-Ping Chen, Pai-Ching Lin, "Tolbutamide Particle And Preparing Method Thereof And Method Of Reducing A Blood Glucose." U.S. Patent US20120121707, issued May 17, 2012.

Artikel (PubMed)

PMID: 19515014
Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1.

Link

DailyMed: tolbutamide tablets

Contoh Produk & Brand

Produk: 9 • International brands: 7

Produk

Mobenol Tablets 500mg

Tablet • 500 mg / tab • Oral • Canada • Approved
Novo-butamide 500mg

Tablet • 500 mg • Oral • Canada • Generic • Approved
Orinase 0.5gm

Tablet • 500 mg / tab • Oral • Canada • Approved
Orinase 1gm

Tablet • 1 g / tab • Oral • Canada • Approved
Tolbutamide

Tablet • 500 mg/1 • Oral • US • Generic • Approved
Tolbutamide

Tablet • 500 mg/1 • Oral • US • Generic • Approved
Tolbutamide

Tablet • 500 mg • Oral • Canada • Approved
Tolbutamide Tab 500mg

Tablet • 500 mg • Oral • Canada • Approved

Menampilkan 8 dari 9 produk.

International Brands

Artosin
Butamide
Diabetol
Dirastan
Glyconon
Orinase
Rastinon

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.