- Overview
- Properties
- Genetics
- Related Genes
- Pathways
- Related Drugs
- Related Diseases
- Datasets
- Downloads/LinkOuts
Overview
| Trade Names: | Aglicid; Apo-Tolbutamide; Arkozal; Artosin; Artozin; Butamid; Butamide; Diaben; Diabetamid; Diabetol; Diabuton; Diasulfon; Dirastan; Dolipol; Drabet; Glyconon; Ipoglicone; Mobenol; Novo-Butamide; Orabet; Oralin; Orezan; Orinase; Orinase Diagnostic; Orinaz; Oterben; Pramidex; Rastinon; Restinon; Sk-tolbutamide; Tol-Tab; Tolbusal; Tolbutamid; Toluina; Tolumid; Toluvan; Tolylsulfonylbutylurea; Willbutamide |
|---|---|
| PharmGKB Accession Id: | PA451718 |
Description
A sulphonylurea hypoglycemic agent with actions and uses similar to those of chlorpropamide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p290) (source: Drug Bank)
Indication
Used as an oral hypoglycemic agent in non-insulin-dependent (type 2) Diabetes Miletus with adult onset. (source: Drug Bank)
ATC Therapeutic Categories
- A10BB:Sulfonamides, urea derivatives
- V04CA:Tests for diabetes
Pharmacology, Interactions, and Contraindications
Mechanism Of Action
Sulfonylureas lower blood glucose in patients with type 2 diabetes 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. (source: Drug Bank)
Pharmacology
Tolbutamide, a second-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. (source: Drug Bank)
Absorption, Distribution, Metabolism, Elimination & Toxicity
Biotransformation
Hepatic (source: Drug Bank)
Protein Binding
96% (source: Drug Bank)
Absorption
Well absorbed. Absorption is unaltered if taken with food but is increased with high pH. (source: Drug Bank)
Toxicity
Oral, mouse: LD<sub>50</sub> = 2600 mg/kg (source: Drug Bank)
Isomeric SMILES Code:
CCCCNC(=O)NS(=O)(=O)c1ccc(cc1)C (source: Drug Bank)
In-Depth Annotations (
)
-
rs1799853
at chr10:96692037
in
CYP2C9
This variant has been shown to influence warfarin dose as well as affecting the clearance of several other drugs.- Variant Name:
- CYP2C9*2; CYP2C9:144Arg>Cys
- Related Drugs:
- fluvastatin, glipizide, phenytoin, tolbutamide, warfarin
- Evidence:
-
http://www.pharmgkb.org/.../variant.jsp#ImportantVariantInformationforCYP2C9-111
-
rs1057910
at chr10:96731043
in
CYP2C9
This variant has been shown to correlate significantly with warfarin dose as well as affecting the clearance of several other drugs.- Variant Name:
- CYP2C9*3; CYP2C9:359Ile>Leu
- Related Drugs:
- fluvastatin, glipizide, phenytoin, tolbutamide, warfarin
- Evidence:
-
http://www.pharmgkb.org/.../variant.jsp#ImportantVariantInformationforCYP2C9-222
Curated Annotations (
)
-
rs41291556
at chr10:96525163
in
CYP2C19
This variant is the defining SNP for CYP2C19*8 and leads to decreased activity and poor metabolizer (PM) phenotype.This variant is associated with a dramatic (approximately 90% and 70%) reduction in the metabolism of S-mephenytoin and tolbutamide in vitro.- Variant Name:
- CYP2C19:358T>C; 12711T>C; W120R; T358C
- Related Drugs:
- mephenytoin, tolbutamide
- Evidence:
-
PMID:10411572
-
rs56337013
at chr10:96602485
in
CYP2C19
This variant is the defining SNP for CYP2C19*5 and contributes to the S-mephenytoin poor metabolizer phenotype in caucasians and chinese. The Arg433 to Trp mutation in the heme-binding region essentially abolishes CYP2C19 activity toward S-mephenytoin and tolbutamide.- Variant Name:
- CYP2C19:1297C>T; R433W
- Related Drugs:
- mephenytoin, tolbutamide
- Evidence:
-
PMID:10022751
Variant names are different names that have been used in the literature and other resources to
refer to the same variant.
The following genes are in curated knowledge about this drug.
| Gene | Relationship | Evidence | |
|---|---|---|---|
|
ABCC8 |
|
Publications |
|
|
CYP1A2 |
|
Publications |
|
CYP2C19 |
|
Publications, Variants |
|
|
CYP2C8 |
|
Publications |
|
|
CYP2C9 |
|
Publications, Variants |
|
|
CYP2D6 |
|
Publications |
|
|
CYP3A4 |
|
Publications |
|
|
RAPGEF4 |
|
Publications |
A list of non-curated publications that mention this drug along with other genes is available.
Drug Targets
| Gene | Description | |
|---|---|---|
| KCNJ1 |
|
(source: Drug Bank) |
PharmGKB Curated Pathways
The following drugs are in curated knowledge about this drug.
| Drug | Relationship | Evidence | |
|---|---|---|---|
|
|
fluvastatin |
|
Publications |
A list of non-curated publications that mention this drug along with other drugs is available.
Drug Interactions
| Drug | Description | |
|---|---|---|
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| somatropin recombinant |
|
Somatropin may antagonize the hypoglycemic effect of Tolbutamide. Dose adjustments of Tolbutamide may be required. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| torasemide |
|
Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Torasemide. Consider alternate therapy or monitor for changes in Torasemide therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed. (source: Drug Bank) |
| trimethoprim |
|
Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Trimethoprim. Consider alternate therapy or monitor for changes in Trimethoprim therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| warfarin |
|
Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Warfarin. Consider alternate therapy or monitor for changes in Warfarin therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed. (source: Drug Bank) |
| 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. (source: Drug Bank) |
| 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. (source: Drug Bank) |
Curated Information
The following diseases are in curated knowledge about this drug.
| Disease | Relationship | Evidence | |
|---|---|---|---|
|
|
Diabetes Mellitus |
|
Publications |
|
|
Diabetes Mellitus, Type 2 |
|
Publications |
Non-Curated Information
A list of non-curated publications that mention this drug along with other diseases is available.
Additional Datasets
These datasets are minimally curated and are sorted alphabetically by title.
LinkOuts
Common Searches
Search PubMed
Search Medline Plus
Search PubChem
Search CTD
Non-Curated Publications
A list of non-curated publications that mention this drug is available.