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Identification
NameTolbutamide
Accession NumberDB01124  (APRD00267)
TypeSmall Molecule
GroupsApproved
Description

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.

Structure
Thumb
Synonyms
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
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Mobenol Tablets 500mgtablet500 mgoralCarter Horner Corp.1957-12-311997-08-14Canada
Novo-butamide 500mgtablet500 mgoralNovopharm Limited1968-12-312005-08-10Canada
Orinase 0.5gmtablet500 mgoralHoechst Canada Inc.1957-12-311997-02-28Canada
Orinase 1gmtablet1 goralHoechst Canada Inc.1966-12-311997-02-28Canada
Tolbutamidetablet500 mgoralAa Pharma Inc1975-12-31Not applicableCanada
Tolbutamide Tab 500mgtablet500 mgoralPro Doc Limitee1962-12-312010-07-13Canada
Tolbutamide Tab 500mgtablet500 mgoralDuchesnay Inc1978-12-312003-07-18Canada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Tolbutamidetablet500 mg/1oralMylan Pharmaceuticals Inc.1989-11-01Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
ArtosinNot Available
ButamideNot Available
DiabetolNot Available
DirastanNot Available
GlycononNot Available
OrinaseNot Available
RastinonNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Tolbutamide sodium
ThumbNot applicableDBSALT001412
Categories
UNII982XCM1FOI
CAS number64-77-7
WeightAverage: 270.348
Monoisotopic: 270.103813142
Chemical FormulaC12H18N2O3S
InChI KeyInChIKey=JLRGJRBPOGGCBT-UHFFFAOYSA-N
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)
IUPAC Name
3-butyl-1-(4-methylbenzenesulfonyl)urea
SMILES
CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as benzenesulfonamides. These are organic compounds containing a sulfonamide group that is S-linked to a benzene ring.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzenesulfonamides
Direct ParentBenzenesulfonamides
Alternative Parents
Substituents
  • Tosyl compound
  • Benzenesulfonamide
  • Toluene
  • Sulfonylurea
  • Aminosulfonyl compound
  • Sulfonyl
  • Sulfonic acid derivative
  • Sulfonamide
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Pharmacology
IndicationFor treatment of NIDDM (non-insulin-dependent diabetes mellitus) in conjunction with diet and exercise.
PharmacodynamicsTolbutamide, 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.
Mechanism of actionSulfonylureas 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.
Related Articles
AbsorptionReadily 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.
Volume of distributionNot Available
Protein bindingApproximately 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.

SubstrateEnzymesProduct
Tolbutamide
4-Hydroxy tolbutamideDetails
Route of eliminationUnchanged 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 lifeApproximately 7 hours with interindividual variations ranging from 4-25 hours. Tolbutamide has the shortest duration of action, 6-12 hours, of the antidiabetic sulfonylureas.
ClearanceNot Available
ToxicityOral, mouse: LD50 = 2600 mg/kg
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated Effects
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeEffectReference(s)
Cytochrome P450 2C9
Gene symbol: CYP2C9
UniProt: P11712
rs1057910 CYP2C9*1C AllelePoor drug metabolizer, lower dose requirements8873220
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9959
Blood Brain Barrier+0.9321
Caco-2 permeable-0.6453
P-glycoprotein substrateNon-substrate0.5333
P-glycoprotein inhibitor INon-inhibitor0.9349
P-glycoprotein inhibitor IINon-inhibitor0.9131
Renal organic cation transporterNon-inhibitor0.8852
CYP450 2C9 substrateSubstrate0.5304
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.7558
CYP450 1A2 substrateNon-inhibitor0.9443
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9504
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9613
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.881
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.781
BiodegradationNot ready biodegradable0.8811
Rat acute toxicity2.0629 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9561
hERG inhibition (predictor II)Non-inhibitor0.9511
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Tabletoral1 g
Tabletoral500 mg/1
Tabletoral500 mg
Prices
Unit descriptionCostUnit
Tolbutamide 500 mg tablet0.4USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point128.5 °CPhysProp
water solubility109 mg/L (at 37 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP2.34HANSCH,C ET AL. (1995)
logS-3.39ADME Research, USCD
pKa5.16SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.202 mg/mLALOGPS
logP2.04ALOGPS
logP2.3ChemAxon
logS-3.1ALOGPS
pKa (Strongest Acidic)4.33ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area75.27 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity70.27 m3·mol-1ChemAxon
Polarizability29.1 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (9.12 KB)
SpectraNot Available
References
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.

US20120121707
General References
  1. 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. [PubMed:19515014 ]
External Links
ATC CodesA10BB03V04CA01
AHFS Codes
  • 68:20.20
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (73.9 KB)
Interactions
Drug Interactions
Drug
AcetohexamideAcetohexamide may increase the hypoglycemic activities of Tolbutamide.
Acetylsalicylic acidAcetylsalicylic acid may increase the hypoglycemic activities of Tolbutamide.
AlogliptinAlogliptin may increase the hypoglycemic activities of Tolbutamide.
AmitriptylineAmitriptyline may increase the hypoglycemic activities of Tolbutamide.
AmodiaquineThe serum concentration of Amodiaquine can be increased when it is combined with Tolbutamide.
AprepitantThe serum concentration of Tolbutamide can be decreased when it is combined with Aprepitant.
AripiprazoleThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Aripiprazole.
Arsenic trioxideThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Arsenic trioxide.
ArticaineThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Articaine.
AsenapineThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Asenapine.
AtazanavirThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Atazanavir.
BendroflumethiazideThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Bendroflumethiazide.
BetamethasoneThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Betamethasone.
BosentanThe serum concentration of Bosentan can be increased when it is combined with Tolbutamide.
BrexpiprazoleThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Brexpiprazole.
BumetanideThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Bumetanide.
BuserelinThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Buserelin.
CanagliflozinCanagliflozin may increase the hypoglycemic activities of Tolbutamide.
CarbocisteineThe risk or severity of adverse effects can be increased when Tolbutamide is combined with Carbocisteine.
CarvedilolThe serum concentration of Carvedilol can be increased when it is combined with Tolbutamide.
CeritinibThe serum concentration of Tolbutamide can be increased when it is combined with Ceritinib.
ChloramphenicolThe metabolism of Tolbutamide can be decreased when combined with Chloramphenicol.
ChlorothiazideThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Chlorothiazide.
ChlorpropamideTolbutamide may increase the hypoglycemic activities of Chlorpropamide.
ChlorthalidoneThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Chlorthalidone.
CimetidineThe serum concentration of Tolbutamide can be increased when it is combined with Cimetidine.
ClozapineThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Clozapine.
CorticotropinThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Corticotropin.
Cortisone acetateThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Cortisone acetate.
Cyproterone acetateThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Cyproterone acetate.
DabrafenibThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Dabrafenib.
DanazolThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Danazol.
DarunavirThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Darunavir.
DesogestrelThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Desogestrel.
DexamethasoneThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Dexamethasone.
DexketoprofenThe risk or severity of adverse effects can be increased when Dexketoprofen is combined with Tolbutamide.
DiazoxideThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Diazoxide.
DiclofenacThe serum concentration of Diclofenac can be increased when it is combined with Tolbutamide.
DienogestThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Dienogest.
DihydrotestosteroneDihydrotestosterone may increase the hypoglycemic activities of Tolbutamide.
DisopyramideTolbutamide may increase the hypoglycemic activities of Disopyramide.
DronabinolThe serum concentration of Dronabinol can be increased when it is combined with Tolbutamide.
DrospirenoneThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Drospirenone.
EpinephrineThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Epinephrine.
ErythromycinTolbutamide may increase the hypoglycemic activities of Erythromycin.
EstradiolThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Estradiol.
Estrone sulfateThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Estropipate.
Etacrynic acidThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Ethacrynic acid.
EthanolThe risk or severity of adverse effects can be increased when Tolbutamide is combined with Ethanol.
Ethinyl EstradiolThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Ethinyl Estradiol.
Ethynodiol diacetateThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Ethynodiol.
EtonogestrelThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Etonogestrel.
EverolimusThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Everolimus.
ExenatideExenatide may increase the hypoglycemic activities of Tolbutamide.
FenofibrateFenofibrate may increase the hypoglycemic activities of Tolbutamide.
FloxuridineThe metabolism of Tolbutamide can be decreased when combined with Floxuridine.
FluconazoleThe metabolism of Tolbutamide can be decreased when combined with Fluconazole.
FludrocortisoneThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Fludrocortisone.
FosamprenavirThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Fosamprenavir.
FosaprepitantThe serum concentration of Tolbutamide can be decreased when it is combined with Fosaprepitant.
FurosemideThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Furosemide.
GliclazideTolbutamide may increase the hypoglycemic activities of Gliclazide.
GlimepirideTolbutamide may increase the hypoglycemic activities of Glimepiride.
GlipizideTolbutamide may increase the hypoglycemic activities of Glipizide.
GliquidoneGliquidone may increase the hypoglycemic activities of Tolbutamide.
GlyburideTolbutamide may increase the hypoglycemic activities of Glyburide.
GoserelinThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Goserelin.
HistrelinThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Histrelin.
HydrochlorothiazideThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Hydrochlorothiazide.
HydrocortisoneThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Hydrocortisone.
Hydroxyprogesterone caproateThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Hydroxyprogesterone caproate.
IloperidoneThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Iloperidone.
IndapamideThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Indapamide.
IndinavirThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Indinavir.
Insulin AspartInsulin Aspart may increase the hypoglycemic activities of Tolbutamide.
Insulin DegludecTolbutamide may increase the hypoglycemic activities of Insulin degludec.
Insulin DetemirInsulin Detemir may increase the hypoglycemic activities of Tolbutamide.
Insulin GlargineTolbutamide may increase the hypoglycemic activities of Insulin Glargine.
Insulin GlulisineInsulin Glulisine may increase the hypoglycemic activities of Tolbutamide.
Insulin HumanTolbutamide may increase the hypoglycemic activities of Insulin Regular.
Insulin LisproTolbutamide may increase the hypoglycemic activities of Insulin Lispro.
LacosamideThe serum concentration of Lacosamide can be increased when it is combined with Tolbutamide.
LanreotideTolbutamide may increase the hypoglycemic activities of Lanreotide.
LeflunomideThe serum concentration of Tolbutamide can be increased when it is combined with Leflunomide.
LeuprolideThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Leuprolide.
LevonorgestrelThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Levonorgestrel.
LinagliptinLinagliptin may increase the hypoglycemic activities of Tolbutamide.
Lipoic AcidLipoic Acid may increase the hypoglycemic activities of Tolbutamide.
LopinavirThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Lopinavir.
LumacaftorThe serum concentration of Tolbutamide can be decreased when it is combined with Lumacaftor.
LurasidoneThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Lurasidone.
MecamylamineThe risk or severity of adverse effects can be increased when Tolbutamide is combined with Mecamylamine.
MecaserminTolbutamide may increase the hypoglycemic activities of Mecasermin.
Medroxyprogesterone acetateThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Medroxyprogesterone Acetate.
Megestrol acetateThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Megestrol acetate.
MestranolThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Mestranol.
MetforminMetformin may increase the hypoglycemic activities of Tolbutamide.
MethotrimeprazineThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Methotrimeprazine.
MethyclothiazideThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Methyclothiazide.
MethylprednisoloneThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Methylprednisolone.
MetolazoneThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Metolazone.
MetreleptinMetreleptin may increase the hypoglycemic activities of Tolbutamide.
MiconazoleMiconazole may increase the hypoglycemic activities of Tolbutamide.
MifepristoneThe serum concentration of Tolbutamide can be increased when it is combined with Mifepristone.
NadololNadolol may increase the hypoglycemic activities of Tolbutamide.
NateglinideTolbutamide may increase the hypoglycemic activities of Nateglinide.
NelfinavirThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Nelfinavir.
NiacinThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Niacin.
NilotinibThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Nilotinib.
NorethisteroneThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Norethindrone.
NorgestimateThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Norgestimate.
OctreotideTolbutamide may increase the hypoglycemic activities of Octreotide.
OlanzapineThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Olanzapine.
OspemifeneThe serum concentration of Ospemifene can be increased when it is combined with Tolbutamide.
OxandroloneOxandrolone may increase the hypoglycemic activities of Tolbutamide.
PaliperidoneThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Paliperidone.
ParecoxibThe serum concentration of Parecoxib can be increased when it is combined with Tolbutamide.
ParoxetineParoxetine may increase the hypoglycemic activities of Tolbutamide.
PasireotideTolbutamide may increase the hypoglycemic activities of Pasireotide.
PegvisomantPegvisomant may increase the hypoglycemic activities of Tolbutamide.
PentamidineTolbutamide may increase the hypoglycemic activities of Pentamidine.
PhenelzinePhenelzine may increase the hypoglycemic activities of Tolbutamide.
PhenytoinThe metabolism of Tolbutamide can be increased when combined with Phenytoin.
PipotiazineThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Pipotiazine.
PorfimerTolbutamide may increase the photosensitizing activities of Porfimer.
PrednisoloneThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Prednisolone.
PrednisoneThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Prednisone.
ProbenecidThe protein binding of Tolbutamide can be decreased when combined with Probenecid.
ProgesteroneThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Progesterone.
QuetiapineThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Quetiapine.
QuinineTolbutamide may increase the hypoglycemic activities of Quinine.
RamelteonThe serum concentration of Ramelteon can be increased when it is combined with Tolbutamide.
RanitidineThe serum concentration of Tolbutamide can be increased when it is combined with Ranitidine.
RepaglinideTolbutamide may increase the hypoglycemic activities of Repaglinide.
Repository corticotropinThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Repository corticotropin.
RifampicinThe serum concentration of Tolbutamide can be decreased when it is combined with Rifampicin.
RisperidoneThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Risperidone.
RitonavirThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Ritonavir.
SaquinavirThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Saquinavir.
SaxagliptinSaxagliptin may increase the hypoglycemic activities of Tolbutamide.
SecobarbitalThe metabolism of Tolbutamide can be increased when combined with Secobarbital.
SildenafilThe metabolism of Sildenafil can be decreased when combined with Tolbutamide.
SirolimusThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Sirolimus.
SitagliptinSitagliptin may increase the hypoglycemic activities of Tolbutamide.
SparfloxacinSparfloxacin may increase the hypoglycemic activities of Tolbutamide.
SulfadiazineTolbutamide may increase the hypoglycemic activities of Sulfadiazine.
SulfamethoxazoleTolbutamide may increase the hypoglycemic activities of Sulfamethoxazole.
SulfisoxazoleTolbutamide may increase the hypoglycemic activities of Sulfisoxazole.
SunitinibTolbutamide may increase the hypoglycemic activities of Sunitinib.
TacrolimusThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Tacrolimus.
TemsirolimusThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Temsirolimus.
TestosteroneTestosterone may increase the hypoglycemic activities of Tolbutamide.
TipranavirThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Tipranavir.
TolazamideTolbutamide may increase the hypoglycemic activities of Tolazamide.
TorasemideThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Torasemide.
TranylcypromineTranylcypromine may increase the hypoglycemic activities of Tolbutamide.
TriamcinoloneThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Triamcinolone.
TrichlormethiazideThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Trichlormethiazide.
TrimethoprimTolbutamide may increase the hypoglycemic activities of Trimethoprim.
TriptorelinThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Triptorelin.
TroglitazoneTroglitazone may increase the hypoglycemic activities of Tolbutamide.
VerteporfinTolbutamide may increase the photosensitizing activities of Verteporfin.
VildagliptinVildagliptin may increase the hypoglycemic activities of Tolbutamide.
VorinostatThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Vorinostat.
ZiprasidoneThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Ziprasidone.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Sulfonylurea receptor activity
Specific Function:
Subunit of the beta-cell ATP-sensitive potassium channel (KATP). Regulator of ATP-sensitive K(+) channels and insulin release.
Gene Name:
ABCC8
Uniprot ID:
Q09428
Molecular Weight:
176990.36 Da
References
  1. Mizuno CS, Chittiboyina AG, Kurtz TW, Pershadsingh HA, Avery MA: Type 2 diabetes and oral antihyperglycemic drugs. Curr Med Chem. 2008;15(1):61-74. [PubMed:18220763 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Phosphatidylinositol-4,5-bisphosphate binding
Specific Function:
In the kidney, probably plays a major role in potassium homeostasis. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive vol...
Gene Name:
KCNJ1
Uniprot ID:
P48048
Molecular Weight:
44794.6 Da
References
  1. Proks P, Jones P, Ashcroft FM: Interaction of stilbene disulphonates with cloned K(ATP) channels. Br J Pharmacol. 2001 Mar;132(5):973-82. [PubMed:11226127 ]
  2. Smith PA, Proks P: Inhibition of the ATP-sensitive potassium channel from mouse pancreatic beta-cells by surfactants. Br J Pharmacol. 1998 Jun;124(3):529-39. [PubMed:9647478 ]
  3. Liu X, Singh BB, Ambudkar IS: ATP-dependent activation of K(Ca) and ROMK-type K(ATP) channels in human submandibular gland ductal cells. J Biol Chem. 1999 Aug 27;274(35):25121-9. [PubMed:10455193 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
References
  1. 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. [PubMed:19515014 ]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  3. Lasker JM, Wester MR, Aramsombatdee E, Raucy JL: Characterization of CYP2C19 and CYP2C9 from human liver: respective roles in microsomal tolbutamide, S-mephenytoin, and omeprazole hydroxylations. Arch Biochem Biophys. 1998 May 1;353(1):16-28. [PubMed:9578596 ]
  4. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme...
Gene Name:
CYP2C8
Uniprot ID:
P10632
Molecular Weight:
55824.275 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 Da
References
  1. 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. [PubMed:19515014 ]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  3. Lasker JM, Wester MR, Aramsombatdee E, Raucy JL: Characterization of CYP2C19 and CYP2C9 from human liver: respective roles in microsomal tolbutamide, S-mephenytoin, and omeprazole hydroxylations. Arch Biochem Biophys. 1998 May 1;353(1):16-28. [PubMed:9578596 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP2C18
Uniprot ID:
P33260
Molecular Weight:
55710.075 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Proton-dependent oligopeptide secondary active transmembrane transporter activity
Specific Function:
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides. May constitute a major route for the absorption of protein digestion end-products.
Gene Name:
SLC15A1
Uniprot ID:
P46059
Molecular Weight:
78805.265 Da
References
  1. Terada T, Sawada K, Saito H, Hashimoto Y, Inui K: Inhibitory effect of novel oral hypoglycemic agent nateglinide (AY4166) on peptide transporters PEPT1 and PEPT2. Eur J Pharmacol. 2000 Mar 24;392(1-2):11-7. [PubMed:10748266 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibited by the grapefruit juice component naringin.
Gene Name:
SLCO1A2
Uniprot ID:
P46721
Molecular Weight:
74144.105 Da
References
  1. Shitara Y, Sugiyama D, Kusuhara H, Kato Y, Abe T, Meier PJ, Itoh T, Sugiyama Y: Comparative inhibitory effects of different compounds on rat oatpl (slc21a1)- and Oatp2 (Slc21a5)-mediated transport. Pharm Res. 2002 Feb;19(2):147-53. [PubMed:11883641 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Peptide:proton symporter activity
Specific Function:
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides.
Gene Name:
SLC15A2
Uniprot ID:
Q16348
Molecular Weight:
81782.77 Da
References
  1. Terada T, Sawada K, Saito H, Hashimoto Y, Inui K: Inhibitory effect of novel oral hypoglycemic agent nateglinide (AY4166) on peptide transporters PEPT1 and PEPT2. Eur J Pharmacol. 2000 Mar 24;392(1-2):11-7. [PubMed:10748266 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS) (By similarity). Mediates the sodium-in...
Gene Name:
SLC22A6
Uniprot ID:
Q4U2R8
Molecular Weight:
61815.78 Da
References
  1. Uwai Y, Saito H, Hashimoto Y, Inui K: Inhibitory effect of anti-diabetic agents on rat organic anion transporter rOAT1. Eur J Pharmacol. 2000 Jun 16;398(2):193-7. [PubMed:10854830 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost.
Gene Name:
SLCO2B1
Uniprot ID:
O94956
Molecular Weight:
76709.98 Da
References
  1. Satoh H, Yamashita F, Tsujimoto M, Murakami H, Koyabu N, Ohtani H, Sawada Y: Citrus juices inhibit the function of human organic anion-transporting polypeptide OATP-B. Drug Metab Dispos. 2005 Apr;33(4):518-23. Epub 2005 Jan 7. [PubMed:15640378 ]
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Drug created on June 13, 2005 07:24 / Updated on November 30, 2015 12:10