Tolbutamide

Identification

Summary

Tolbutamide is a sulfonylurea used to treat hyperglycemia in patients with type 2 diabetes mellitus.

Generic Name

Tolbutamide

DrugBank Accession Number

DB01124

Background

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.

Type

Small Molecule

Groups

Approved, Investigational

Structure

Similar Structures

Weight: Average: 270.348
Monoisotopic: 270.103813142
Chemical Formula: C₁₂H₁₈N₂O₃S

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
Tolbutamida
Tolbutamide
Tolbutamidum
Tolylsulfonylbutylurea

External IDs

NSC-23813
NSC-87833

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Pharmacology

Indication

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

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Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Management of	Type 2 diabetes mellitus		••••••••••••

Contraindications & Blackbox Warnings

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Pharmacodynamics

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.

Mechanism of action

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.

Target	Actions	Organism
AATP-binding cassette sub-family C member 8	inhibitor	Humans
UATP-sensitive inward rectifier potassium channel 1	inhibitor	Humans

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.

Volume of distribution

Not Available

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.

Hover over products below to view reaction partners

Tolbutamide
- 4-Hydroxy tolbutamide

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.

Clearance

Not Available

Adverse Effects

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Toxicity

Oral, mouse: LD₅₀ = 2600 mg/kg

Pathways

Not Available

Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">

Interacting Gene/Enzyme	Allele name	Genotype(s)	Defining Change(s)	Type(s)	Description	Details
Cytochrome P450 2C9	CYP2C9*3	(C;C) / (A;C)	C Allele	Effect Directly Studied	Patients with this genotype have reduced metabolism of tolbutamide.	Details
Cytochrome P450 2C9	CYP2C9*6	Not Available	818delA	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*15	Not Available	485C>A	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*25	Not Available	353_362delAGAAATGGAA	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*35	Not Available	374G>T / 430C>T	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*2	Not Available	430C>T	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*4	Not Available	1076T>C	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*5	Not Available	1080C>G	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*8	Not Available	449G>A	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*11	Not Available	1003C>T	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*12	Not Available	1465C>T	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*13	Not Available	269T>C	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*14	Not Available	374G>A	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*16	Not Available	895A>G	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*18	Not Available	1075A>C / 1190A>C … show all	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*26	Not Available	389C>G	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*28	Not Available	641A>T	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*30	Not Available	1429G>A	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*33	Not Available	395G>A	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details

Interactions

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This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
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Abacavir	Abacavir may decrease the excretion rate of Tolbutamide which could result in a higher serum level.
Abatacept	The metabolism of Tolbutamide can be increased when combined with Abatacept.
Abiraterone	The metabolism of Tolbutamide can be decreased when combined with Abiraterone.
Abrocitinib	The metabolism of Abrocitinib can be decreased when combined with Tolbutamide.
Acarbose	The risk or severity of hypoglycemia can be increased when Acarbose is combined with Tolbutamide.

Food Interactions

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

Products

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Product Ingredients

Ingredient	UNII	CAS	InChI Key
Tolbutamide sodium	E830VC49W5	473-41-6	QKHDBRQBSNZFAK-UHFFFAOYSA-M

International/Other Brands

Artosin / Butamide / Diabetol / Dirastan / Glyconon / Orinase / Rastinon

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Mobenol Tablets 500mg	Tablet	500 mg / tab	Oral	Carter Horner Corp.	1957-12-31	1997-08-14
Orinase 0.5gm	Tablet	500 mg / tab	Oral	Hoechst Canada Inc.	1957-12-31	1997-02-28
Orinase 1gm	Tablet	1 g / tab	Oral	Hoechst Canada Inc.	1966-12-31	1997-02-28
Tolbutamide	Tablet	500 mg	Oral	Aa Pharma Inc	1975-12-31	Not applicable
Tolbutamide Tab 500mg	Tablet	500 mg	Oral	Duchesnay Inc.	1978-12-31	2003-07-18

Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Novo-butamide 500mg	Tablet	500 mg	Oral	Novopharm Limited	1968-12-31	2005-08-10
Tolbutamide	Tablet	500 mg/1	Oral	Mylan Pharmaceuticals Inc.	1989-11-01	2021-09-30
Tolbutamide	Tablet	500 mg/1	Oral	Physicians Total Care, Inc.	1979-05-01	2012-06-30

Chemical Identifiers

UNII: 982XCM1FOI
CAS number: 64-77-7
InChI Key: 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

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

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. [Article]
DailyMed: tolbutamide tablets [Link]

External Links

Human Metabolome Database: HMDB0015256
KEGG Drug: D00380
KEGG Compound: C07148
PubChem Compound: 5505
PubChem Substance: 46508421
ChemSpider: 5304
BindingDB: 50027886
RxNav: 10635
ChEBI: 27999
ChEMBL: CHEMBL782
ZINC: ZINC000001530703
Therapeutic Targets Database: DAP000136
PharmGKB: PA451718
Guide to Pharmacology: GtP Drug Page
Drugs.com: Drugs.com Drug Page
Wikipedia: Tolbutamide

MSDS

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Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
4	Completed	Basic Science	Type 2 Diabetes Mellitus	1
2	Completed	Treatment	Impaired Glucose Tolerance / Type 2 Diabetes Mellitus	1
1	Completed	Not Available	Chronic Pain	1
1	Completed	Basic Science	Drug Drug Interaction (DDI)	2
1	Completed	Basic Science	Healthy Subjects (HS)	2

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Direct Dispensing Inc.
Ivax Pharmaceuticals
Kaiser Foundation Hospital
Major Pharmaceuticals
Mylan
Pharmaceutical Utilization Management Program VA Inc.
Pharmacia Inc.
Pharmedix
Physicians Total Care Inc.
UDL Laboratories

Dosage Forms

Form	Route	Strength
Tablet	Oral	500 mg / tab
Tablet	Oral	1 g / tab
Tablet	Oral
Tablet	Oral	500 mg/1
Tablet	Oral	500 mg

Prices

Unit description	Cost	Unit
Tolbutamide 500 mg tablet	0.4USD	tablet

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	128.5 °C	PhysProp
water solubility	109 mg/L (at 37 °C)	YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP	2.34	HANSCH,C ET AL. (1995)
logS	-3.39	ADME Research, USCD
pKa	5.16	SANGSTER (1994)

Predicted Properties

Property	Value	Source
Water Solubility	0.202 mg/mL	ALOGPS
logP	2.04	ALOGPS
logP	2.3	Chemaxon
logS	-3.1	ALOGPS
pKa (Strongest Acidic)	4.33	Chemaxon
Physiological Charge	-1	Chemaxon
Hydrogen Acceptor Count	3	Chemaxon
Hydrogen Donor Count	2	Chemaxon
Polar Surface Area	75.27 Å²	Chemaxon
Rotatable Bond Count	4	Chemaxon
Refractivity	70.27 m³·mol^-1	Chemaxon
Polarizability	29.1 Å³	Chemaxon
Number of Rings	1	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	Yes	Chemaxon
Ghose Filter	Yes	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	+	0.9959
Blood Brain Barrier	+	0.9321
Caco-2 permeable	-	0.6453
P-glycoprotein substrate	Non-substrate	0.5333
P-glycoprotein inhibitor I	Non-inhibitor	0.9349
P-glycoprotein inhibitor II	Non-inhibitor	0.9131
Renal organic cation transporter	Non-inhibitor	0.8852
CYP450 2C9 substrate	Substrate	0.5304
CYP450 2D6 substrate	Non-substrate	0.9116
CYP450 3A4 substrate	Non-substrate	0.7558
CYP450 1A2 substrate	Non-inhibitor	0.9443
CYP450 2C9 inhibitor	Non-inhibitor	0.9071
CYP450 2D6 inhibitor	Non-inhibitor	0.9504
CYP450 2C19 inhibitor	Non-inhibitor	0.9025
CYP450 3A4 inhibitor	Non-inhibitor	0.9613
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.881
Ames test	Non AMES toxic	0.9133
Carcinogenicity	Non-carcinogens	0.781
Biodegradation	Not ready biodegradable	0.8811
Rat acute toxicity	2.0629 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9561
hERG inhibition (predictor II)	Non-inhibitor	0.9511

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Download (9.12 KB)

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	splash10-0a4m-9620000000-80b8e46fa29dc771af14
LC-MS/MS Spectrum - LC-ESI-qTof , Positive	LC-MS/MS	splash10-0006-0190000000-7ff8ebe7a2c8d9b989ec
LC-MS/MS Spectrum - LC-ESI-qTof , Positive	LC-MS/MS	splash10-05fr-1920000000-defac8a82087405b74df
MS/MS Spectrum - , positive	LC-MS/MS	splash10-0006-0190000000-7ff8ebe7a2c8d9b989ec
MS/MS Spectrum - , positive	LC-MS/MS	splash10-05fr-1920000000-defac8a82087405b74df
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0a4l-8910000000-2c79e946070cef280fb6
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-01di-5890000000-91a371c009eb2a3bd9f8
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0006-9100000000-6c269b9d8265a72e0766
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-00di-1900000000-7268df4dbc0da20048ad
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0006-9000000000-9ec1f924fed9013a43c3
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0006-9600000000-07859ccef399ce236cc9
Predicted 1H NMR Spectrum	1D NMR	Not Applicable
Predicted 13C NMR Spectrum	1D NMR	Not Applicable

Chromatographic Properties

Collision Cross Sections (CCS)

Adduct	CCS Value (Å²)	Source type	Source
[M-H]-	172.9785055	predicted	DarkChem Lite v0.1.0
[M-H]-	173.1721055	predicted	DarkChem Lite v0.1.0
[M-H]-	172.5564055	predicted	DarkChem Lite v0.1.0
[M-H]-	164.6898	predicted	DeepCCS 1.0 (2019)
[M+H]+	173.8141055	predicted	DarkChem Lite v0.1.0
[M+H]+	174.0795055	predicted	DarkChem Lite v0.1.0
[M+H]+	173.8530055	predicted	DarkChem Lite v0.1.0
[M+H]+	167.0478	predicted	DeepCCS 1.0 (2019)
[M+Na]+	173.1745055	predicted	DarkChem Lite v0.1.0
[M+Na]+	172.6839055	predicted	DarkChem Lite v0.1.0
[M+Na]+	173.14095	predicted	DeepCCS 1.0 (2019)

Targets

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Details1. ATP-binding cassette sub-family C member 8

Kind: Protein
Organism: Humans
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
Uniprot Name: ATP-binding cassette sub-family C member 8
Molecular Weight: 176990.36 Da

References

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. [Article]

Details2. ATP-sensitive inward rectifier potassium channel 1

Kind: Protein
Organism: Humans
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...
Gene Name: KCNJ1
Uniprot ID: P48048
Uniprot Name: ATP-sensitive inward rectifier potassium channel 1
Molecular Weight: 44794.6 Da

References

Proks P, Jones P, Ashcroft FM: Interaction of stilbene disulphonates with cloned K(ATP) channels. Br J Pharmacol. 2001 Mar;132(5):973-82. [Article]
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. [Article]
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. [Article]

Enzymes

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	70000	N/A	N/A	A27494

Details1. Cytochrome P450 2C9

Kind: Protein
Organism: Humans
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 un...
Gene Name: CYP2C9
Uniprot ID: P11712
Uniprot Name: Cytochrome P450 2C9
Molecular Weight: 55627.365 Da

References

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. [Article]
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. [Article]
Fischer V, Johanson L, Heitz F, Tullman R, Graham E, Baldeck JP, Robinson WT: The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor fluvastatin: effect on human cytochrome P-450 and implications for metabolic drug interactions. Drug Metab Dispos. 1999 Mar;27(3):410-6. [Article]
McKillop D, Wild MJ, Butters CJ, Simcock C: Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53. doi: 10.1080/004982598239092 . [Article]
Grimm SW, Dyroff MC: Inhibition of human drug metabolizing cytochromes P450 by anastrozole, a potent and selective inhibitor of aromatase. Drug Metab Dispos. 1997 May;25(5):598-602. [Article]
Horsmans Y, Kanyinda JM, Desager JP: Relationship between mephenytoin, phenytoin and tolbutamide hydroxylations in healthy African subjects. Pharmacol Toxicol. 1996 Feb;78(2):86-8. [Article]
Clin-Info. (2006). In Compendium of Pharmaceuticals and Specialties: The Canadian Drug Reference for Health Professionals (pp. L58). Canadian Pharmacists Association. [ISBN:1-894402-22-7]
Flockhart Table of Drug Interactions [Link]

Details2. Cytochrome P450 2C8

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Inhibitor
Curator comments: In vitro studies suggest weak inhibition of CYP2C8 and the clinical relevance of this finding in drug interactions is unknown.

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 un...
Gene Name: CYP2C8
Uniprot ID: P10632
Uniprot Name: Cytochrome P450 2C8
Molecular Weight: 55824.275 Da

References

Komatsu K, Ito K, Nakajima Y, Kanamitsu Si, Imaoka S, Funae Y, Green CE, Tyson CA, Shimada N, Sugiyama Y: Prediction of in vivo drug-drug interactions between tolbutamide and various sulfonamides in humans based on in vitro experiments. Drug Metab Dispos. 2000 Apr;28(4):475-81. [Article]
Rahman A, Korzekwa KR, Grogan J, Gonzalez FJ, Harris JW: Selective biotransformation of taxol to 6 alpha-hydroxytaxol by human cytochrome P450 2C8. Cancer Res. 1994 Nov 1;54(21):5543-6. [Article]
Prueksaritanont T, Ma B, Tang C, Meng Y, Assang C, Lu P, Reider PJ, Lin JH, Baillie TA: Metabolic interactions between mibefradil and HMG-CoA reductase inhibitors: an in vitro investigation with human liver preparations. Br J Clin Pharmacol. 1999 Mar;47(3):291-8. doi: 10.1046/j.1365-2125.1999.00903.x. [Article]
Clin-Info. (2006). In Compendium of Pharmaceuticals and Specialties: The Canadian Drug Reference for Health Professionals (pp. L58). Canadian Pharmacists Association. [ISBN:1-894402-22-7]

Details3. Cytochrome P450 2C19

Kind: Protein
Organism: Humans
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 im...
Gene Name: CYP2C19
Uniprot ID: P33261
Uniprot Name: Cytochrome P450 2C19
Molecular Weight: 55930.545 Da

References

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. [Article]
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. [Article]
Wester MR, Lasker JM, Johnson EF, Raucy JL: CYP2C19 participates in tolbutamide hydroxylation by human liver microsomes. Drug Metab Dispos. 2000 Mar;28(3):354-9. [Article]
Komatsu K, Ito K, Nakajima Y, Kanamitsu Si, Imaoka S, Funae Y, Green CE, Tyson CA, Shimada N, Sugiyama Y: Prediction of in vivo drug-drug interactions between tolbutamide and various sulfonamides in humans based on in vitro experiments. Drug Metab Dispos. 2000 Apr;28(4):475-81. [Article]
Canadian Pharmacists Association (2006). Compendium of Pharmaceuticals and Specialties: The Canadian Drug Reference for Health Professionals. Canadian Pharmacists Association. [ISBN:1-894402-22-7]

Details4. Cytochrome P450 2C18

Kind: Protein
Organism: Humans
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 un...
Gene Name: CYP2C18
Uniprot ID: P33260
Uniprot Name: Cytochrome P450 2C18
Molecular Weight: 55710.075 Da

References

Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]

Carriers

Property	Measurement	pH	Temperature (°C)	References
Kd (nM)	6026	N/A	N/A	A28335

Details1. Serum albumin

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Toxic substance binding
Specific Function: Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name: ALB
Uniprot ID: P02768
Uniprot Name: Serum albumin
Molecular Weight: 69365.94 Da

References

Marszall MP, Bucinski A: A protein-coated magnetic beads as a tool for the rapid drug-protein binding study. J Pharm Biomed Anal. 2010 Jul 8;52(3):420-4. doi: 10.1016/j.jpba.2009.06.023. Epub 2009 Jun 18. [Article]
Joseph KS, Hage DS: Characterization of the binding of sulfonylurea drugs to HSA by high-performance affinity chromatography. J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Jun 1;878(19):1590-8. doi: 10.1016/j.jchromb.2010.04.019. [Article]
Yoo MJ, Hage DS: Use of peak decay analysis and affinity microcolumns containing silica monoliths for rapid determination of drug-protein dissociation rates. J Chromatogr A. 2011 Apr 15;1218(15):2072-8. doi: 10.1016/j.chroma.2010.09.070. Epub 2010 Oct 16. [Article]
Basiaga SB, Hage DS: Chromatographic studies of changes in binding of sulfonylurea drugs to human serum albumin due to glycation and fatty acids. J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Nov 15;878(30):3193-7. doi: 10.1016/j.jchromb.2010.09.033. Epub 2010 Oct 23. [Article]

Transporters

Details1. Solute carrier family 15 member 1

Kind: Protein
Organism: Humans
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
Uniprot Name: Solute carrier family 15 member 1
Molecular Weight: 78805.265 Da

References

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. [Article]

Details2. Solute carrier organic anion transporter family member 1A2

Kind: Protein
Organism: Humans
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 inhibit...
Gene Name: SLCO1A2
Uniprot ID: P46721
Uniprot Name: Solute carrier organic anion transporter family member 1A2
Molecular Weight: 74144.105 Da

References

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. [Article]

Details3. Solute carrier family 22 member 6

Kind: Protein
Organism: Humans
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 ...
Gene Name: SLC22A6
Uniprot ID: Q4U2R8
Uniprot Name: Solute carrier family 22 member 6
Molecular Weight: 61815.78 Da

References

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. [Article]

Details4. Solute carrier family 15 member 2

Kind: Protein
Organism: Humans
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
Uniprot Name: Solute carrier family 15 member 2
Molecular Weight: 81782.77 Da

References

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. [Article]

Details5. Solute carrier organic anion transporter family member 2B1

Kind: Protein
Organism: Humans
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
Uniprot Name: Solute carrier organic anion transporter family member 2B1
Molecular Weight: 76709.98 Da

References

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. [Article]

Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:55

Tolbutamide

Identification

Structure for Tolbutamide (DB01124)

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Collision Cross Sections (CCS)

Targets

References

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Enzymes

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Carriers

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Transporters

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