Tolbutamide

Các tên gọi khác (18 ) :

1-Butyl-3-(P-methylphenylsulfonyl)urea
1-Butyl-3-(P-tolylsulfonyl)urea
1-Butyl-3-tosylurea
1-P-Toluenesulfonyl-3-butylurea
3-(P-Tolyl-4-sulfonyl)-1-butylurea
N-(4-Methylbenzenesulfonyl)-n'-butylurea
N-(4-Methylphenylsulfonyl)-n'-butylurea
N-(P-Methylbenzenesulfonyl)-n'-butylurea
N-(Sulfonyl-P-methylbenzene)-n'-N-butylurea
N-Butyl-n'-(4-methylphenylsulfonyl)urea
N-Butyl-N'-(p-tolylsulfonyl)urea
N-Butyl-n'-P-toluenesulfonylurea
N-N-Butyl-n'-tosylurea
Orinase (tn)
Tolbutamida
Tolbutamide
Tolbutamidum
Tolylsulfonylbutylurea

Insulin và nhóm Thuốc hạ đường huyết

Thuốc Gốc

Small Molecule

CAS: 64-77-7

ATC: A10BB03, V04CA01

ĐG : Direct Dispensing Inc.

CTHH: C₁₂H₁₈N₂O₃S

PTK: 270.348

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 β 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 β 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.

Nhận Dạng Quốc Tế & Đặc Tính Hóa Học

Công thức hóa học

C₁₂H₁₈N₂O₃S

Phân tử khối

270.348

Monoisotopic mass

270.103813142

InChI

InChI=1S/C12H18N2O3S/c1-3-4-9-13-12(15)14-18(16,17)11-7-5-10(2)6-8-11/h5-8H,3-4,9H2,1-2H3,(H2,13,14,15)

InChI Key

InChIKey=JLRGJRBPOGGCBT-UHFFFAOYSA-N

IUPAC Name

3-butyl-1-[(4-methylbenzene)sulfonyl]urea

Traditional IUPAC Name

3-butyl-1-(4-methylbenzenesulfonyl)urea

SMILES

CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1

Độ tan chảy

128.5 °C

Độ hòa tan

109 mg/L (at 37 °C)

logP

2.34

logS

-3.39

pKa (strongest acidic)

4.33

PSA

75.27 Å²

Refractivity

70.27 m³·mol^-1

Polarizability

29.1 Å³

Rotatable Bond Count

H Bond Acceptor Count

H Bond Donor Count

Physiological Charge

-1

Number of Rings

Bioavailability

Rule of Five

true

Ghose Filter

true

pKa

5.16

Dược Lực Học : Tolbutamide, a first-generation sulfonylurea antidiabetic agent, is used with diet to lower blood glucose levels in patients with diabetes mellitus type II. Tolbutamide is twice as potent as the related second-generation agent glipizide. Tolbutamide lowers blood sugar by stimulating the pancreas to secrete insulin and helping the body use insulin efficiently. The pancreas must be able to produce insulin for this drug to work.

Cơ Chế Tác Dụng : 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 β 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 β 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. Sulfonylureas lower blood glucose in patients with NIDDM by directly stimulating the acute release of insulin from functioning beta cells of pancreatic islet tissue by an unknown process that involves a sulfonylurea receptor (receptor 1) on the beta cell. Sulfonylureas inhibit the ATP-potassium channels on the beta cell membrane and potassium efflux, which results in depolarization and calcium influx, calcium-calmodulin binding, kinase activation, and release of insulin-containing granules by exocytosis, an effect similar to that of glucose.

Dược Động Học :

▧ Absorption :
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.
▧ Protein binding :
Approximately 95% bound to plasma proteins.
▧ Metabolism :
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.
▧ Route of Elimination :
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.
▧ 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.

Độc Tính : Oral, mouse: LD₅₀ = 2600 mg/kg

Chỉ Định : For treatment of NIDDM (non-insulin-dependent diabetes mellitus) in conjunction with diet and exercise.

Tương Tác Thuốc :

Acebutolol Acebutolol may decrease symptoms of hypoglycemia and increase the time required for the body to compensate for hypoglycemia.
Acenocoumarol Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Acenocoumarol. Consider alternate therapy or monitor for changes in Acenocoumarol therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
Acetylsalicylic acid Acetylsalicylic acid increases the effect of the sulfonylurea, tolbutamide.
Atenolol The beta-blocker, atenolol, may decrease symptoms of hypoglycemia.
Bisoprolol The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.
Bosentan Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Bosentan. Consider alternate therapy or monitor for changes in Bosentan therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
Capecitabine Capecitabine, 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 Capecitabine is initiated, discontinued or dose changed.
Carvedilol The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
Celecoxib Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Celecoxib. Consider alternate therapy or monitor for changes in Celecobix therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
Chloramphenicol Chloramphenicol may increase the effect of sulfonylurea, tolbutamide.
Clofibrate Clofibrate may increase the effect of sulfonylurea, tolbutamide.
Dapsone Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Dapsone. Consider alternate therapy or monitor for changes in Dapsone therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
Delavirdine Delavirdine, 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 Delavirdine is initiated, discontinued or dose changed.
Digoxin Tolbutamide increases the effect of digoxin
Esmolol The beta-blocker, esmolol, may decrease symptoms of hypoglycemia.
Floxuridine Floxuridine, 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 Floxuridine is initiated, discontinued or dose changed.
Fluconazole Fluconazole, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Tolbutamide, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in Fluconazole therapeutic and adverse effects if Delavirdine is initiated, discontinued or dose changed.
Fluorouracil Fluorouracil, 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 Fluorouracil is initiated, discontinued or dose changed.
Fluoxetine Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Fluoxetine. Consider alternate therapy or monitor for changes in Fluoxetine therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
Flurbiprofen Flurbiprofen, 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 Flurbiprofen is initiated, discontinued or dose changed.
Fosphenytoin Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Fosphenytoin. Consider alternate therapy or monitor for changes in Fosphenytoin therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
Gemfibrozil Gemfibrozil, 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 Gemfibrozil is initiated, discontinued or dose changed.
Glimepiride Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Glimepiride. Consider alternate therapy or monitor for changes in Glimepiride therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
Glipizide Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Glipizide. Consider alternate therapy or monitor for changes in Glipizide therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
Ibuprofen Ibuprofen, 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 Ibuprofen is initiated, discontinued or dose changed.
Indomethacin 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.
Ketamine Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Ketamine. Consider alternate therapy or monitor for changes in Ketamine therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
Ketoconazole Ketoconazole, 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 Ketoconazole is initiated, discontinued or dose changed.
Labetalol The beta-blocker, labetalol, may decrease symptoms of hypoglycemia.
Losartan Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Losartan. Consider alternate therapy or monitor for changes in Losartan therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
Lumiracoxib Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Lumiracoxib. Consider alternate therapy or monitor for changes in Lumiracoxib therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
Mefenamic acid Mefanamic acid, 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 Mefanamic acid is initiated, discontinued or dose changed.
Mestranol Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Mestranol. Consider alternate therapy or monitor for changes in Mestranol therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
Metoprolol The beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.
Miconazole Miconazole, 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 Miconazole is initiated, discontinued or dose changed.
Montelukast Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Montelukast. Consider alternate therapy or monitor for changes in Montelukast therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
Nadolol The beta-blocker, nadolol, may decrease symptoms of hypoglycemia.
Nateglinide Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Nateglinide. Consider alternate therapy or monitor for changes in Nateglinide therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
Nicardipine Nicardipine, 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 Nicardipine is initiated, discontinued or dose changed.
Oxprenolol The beta-blocker, oxprenolol, may decrease symptoms of hypoglycemia.
Paclitaxel Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Paclitaxel. Consider alternate therapy or monitor for changes in Paclitaxel therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
Phenylbutazone Phenylbutazone increases the effect of the hypoglycemic agent
Phenytoin Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Phenytoin. Consider alternate therapy or monitor for changes in Phenytoin therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
Pindolol The beta-blocker, pindolol, may decrease symptoms of hypoglycemia.
Piroxicam Piroxicam, 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 Piroxicam is initiated, discontinued or dose changed.
Propranolol The beta-blocker, propranolol, may decrease symptoms of hypoglycemia.
Rifampicin Rifampin may decrease the effect of sulfonylurea, tolbutamide.
Sitaxentan Sitaxsentan, 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 Sitaxsentan is initiated, discontinued or dose changed.
Somatropin recombinant Somatropin may antagonize the hypoglycemic effect of Tolbutamide. Dose adjustments of Tolbutamide may be required.
Sulfadiazine Tolbutamide and Sulfadiazine are strong CYP2C9 inhibitors and substrates. Decreased metabolism and clearance of both agents may occur during concomitant therapy. Consider alternate therpy or monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or dose(s) changed.
Sulfamethoxazole Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Sulfamethoxazole. Consider alternate therapy or monitor for changes in Sulfamethoxazole therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
Sulfinpyrazone Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Sulfinpyrazone. Consider alternate therapy or monitor for changes in Sulfinpyrazone therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
Sulfisoxazole Tolbutamide and Sulfisoxazole are strong CYP2C9 inhibitors and substrates. Decreased metabolism and clearance of both agents may occur during concomitant therapy. Consider alternate therpy or monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or dose(s) changed.
Tamoxifen Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Tamoxifen. Consider alternate therapy or monitor for changes in Tamoxifen therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
Timolol The beta-blocker, timolol, may decrease symptoms of hypoglycemia.
Torasemide Tolbutamide, a strong CYP2C9 inhibitor, may increase the serum concentration of Torasemide, a CYP2C9 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Torasemide if Tolbutamide is initiated, discontinued or dose changed.
Trimethoprim The strong CYP2C9 inhibitor, Tolbutamide, 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 Tolbutamide is initiated, discontinued or dose changed.
Voriconazole Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Voriconazole. Consider alternate therapy or monitor for changes in Voriconazole therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
Warfarin Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism of warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if tolbutamide is initiated, discontinued or dose changed.
Zafirlukast Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of zafirlukast. Consider alternate therapy or monitor for changes in zafirlukast therapeutic and adverse effects if tolbutamide is initiated, discontinued or dose changed.
Zopiclone Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Zopiclone. Consider alternate therapy or monitor for changes in Zopiclone therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.

Liều Lượng & Cách Dùng : Tablet - Oral - 500 mg

Dữ Kiện Thương Mại

Giá thị trường

Biệt dược thương mại : Tolbutamide 500 mg tablet

Giá bán buôn : USD >0.4

Đơn vị tính : tablet

Nhà Sản Xuất

Công ty :

Sản phẩm biệt dược : Artosin
Công ty :

Sản phẩm biệt dược : Butamide
Công ty :

Sản phẩm biệt dược : Diabetol
Công ty :

Sản phẩm biệt dược : Dirastan
Công ty :

Sản phẩm biệt dược : Glyconon
Công ty :

Sản phẩm biệt dược : Orinase
Công ty :

Sản phẩm biệt dược : Rastinon

Đóng gói

Công ty : Direct Dispensing Inc.
Công ty : Ivax Pharmaceuticals
Công ty : Kaiser Foundation Hospital
Công ty : Major Pharmaceuticals

Website : http://www.majorpharmaceuticals.com
Công ty : Mylan

Website : http://www.mylan.com
Công ty : Pharmaceutical Utilization Management Program VA Inc.
Công ty : Pharmacia Inc.

Website : http://www.pharmaciaupjohn.com
Công ty : Pharmedix

Website : http://www.pharmedixrx.com
Công ty : Physicians Total Care Inc.

Website : http://www.physicianstotalcare.com
Công ty : UDL Laboratories

Website : http://www.udllabs.com

Tài Liệu Tham Khảo Thêm

drugbank

http://www.drugbank.ca/drugs/DB01124

PubChem Compound

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=5505

PubChem Substance

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46508421

KEGG Compound

http://www.genome.jp/dbget-bin/www_bget?cpd:C07148

KEGG Drug

http://www.genome.jp/dbget-bin/www_bget?drug:D00380

ChemSpider

http://www.chemspider.com/Chemical-Structure.5304.html

National Drug Code Directory

http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0378-0215-01

PharmGKB

http://www.pharmgkb.org/drug/PA451718

Wikipedia

http://en.wikipedia.org/wiki/Tolbutamide

Drugs.com

http://www.drugs.com/cdi/tolbutamide.html

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