Identification

Name
Tolbutamide
Accession Number
DB01124  (APRD00267)
Type
Small Molecule
Groups
Approved, Investigational
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 IDs
NSC-23813 / NSC-87833
Product Ingredients
IngredientUNIICASInChI Key
Tolbutamide sodiumE830VC49W5473-41-6QKHDBRQBSNZFAK-UHFFFAOYSA-M
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Mobenol Tablets 500mgTablet500 mgOralCarter Horner Corp.1957-12-311997-08-14Canada
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 mgOralDuchesnay Inc.1978-12-312003-07-18Canada
Tolbutamide Tab 500mgTablet500 mgOralPro Doc Limitee1962-12-312010-07-13Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Novo-butamide 500mgTablet500 mgOralNovopharm Limited1968-12-312005-08-10Canada
TolbutamideTablet500 mg/1OralMylan Pharmaceuticals1989-11-01Not applicableUs
TolbutamideTablet500 mg/1OralPhysicians Total Care, Inc.1979-05-012012-06-30Us
International/Other Brands
Artosin / Butamide / Diabetol / Dirastan / Glyconon / Orinase / Rastinon
Categories
UNII
982XCM1FOI
CAS number
64-77-7
Weight
Average: 270.348
Monoisotopic: 270.103813142
Chemical Formula
C12H18N2O3S
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

Pharmacology

Indication

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

Associated Conditions
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.

TargetActionsOrganism
AATP-binding cassette sub-family C member 8
inhibitor
Human
UATP-sensitive inward rectifier potassium channel 1
inhibitor
Human
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.

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
Toxicity

Oral, mouse: LD50 = 2600 mg/kg

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 2C9CYP2C9*3(C;C) / (A;C)C AlleleEffect Directly StudiedPatients with this genotype have reduced metabolism of tolbutamide.Details
Cytochrome P450 2C9CYP2C9*6Not Available818delAEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*15Not Available485C>AEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*25Not Available353_362delAGAAATGGAAEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*35Not Available374G>T / 430C>TEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*2Not Available430C>TEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*4Not Available1076T>CEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*5Not Available1080C>GEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*8Not Available449G>AEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*11Not Available1003C>TEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*12Not Available1465C>TEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*13Not Available269T>CEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*14Not Available374G>AEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*16Not Available895A>GEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*18Not Available1075A>C / 1190A>C  … show all Effect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*26Not Available389C>GEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*28Not Available641A>TEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*30Not Available1429G>AEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2C9CYP2C9*33Not Available395G>AEffect InferredPoor drug metabolizer, lower dose requirementsDetails

Interactions

Drug Interactions
DrugInteraction
(1S,6R)-3-{[3-(TRIFLUOROMETHYL)-5,6-DIHYDRO[1,2,4]TRIAZOLO[4,3-A]PYRAZIN-7(8H)-YL]CARBONYL}-6-(2,4,5-TRIFLUOROPHENYL)CYCLOHEX-3-EN-1-AMINE(1S,6R)-3-{[3-(TRIFLUOROMETHYL)-5,6-DIHYDRO[1,2,4]TRIAZOLO[4,3-A]PYRAZIN-7(8H)-YL]CARBONYL}-6-(2,4,5-TRIFLUOROPHENYL)CYCLOHEX-3-EN-1-AMINE may increase the hypoglycemic activities of Tolbutamide.
2,4-thiazolidinedione2,4-thiazolidinedione may increase the hypoglycemic activities of Tolbutamide.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the hypoglycemic activities of Tolbutamide.
AbirateroneThe serum concentration of Tolbutamide can be increased when it is combined with Abiraterone.
AcarboseAcarbose may increase the hypoglycemic activities of Tolbutamide.
AcebutololAcebutolol may increase the hypoglycemic activities of Tolbutamide.
AceclofenacThe metabolism of Aceclofenac can be decreased when combined with Tolbutamide.
AcenocoumarolTolbutamide may increase the anticoagulant activities of Acenocoumarol.
AcetaminophenAcetaminophen may decrease the excretion rate of Tolbutamide which could result in a higher serum level.
AcetazolamideThe therapeutic efficacy of Tolbutamide can be increased when used in combination with Acetazolamide.
Food Interactions
Not 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
Human Metabolome Database
HMDB0015256
KEGG Drug
D00380
KEGG Compound
C07148
PubChem Compound
5505
PubChem Substance
46508421
ChemSpider
5304
BindingDB
50027886
ChEBI
27999
ChEMBL
CHEMBL782
Therapeutic Targets Database
DAP000136
PharmGKB
PA451718
IUPHAR
2415
Guide to Pharmacology
GtP Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Tolbutamide
ATC Codes
A10BB03 — TolbutamideV04CA01 — Tolbutamide
AHFS Codes
  • 68:20.20 — Sulfonylureas
MSDS
Download (73.9 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentDrug Interaction Potential1
1CompletedNot AvailablePain, Chronic1
1CompletedBasic ScienceDrug Drug Interactions1
1CompletedBasic ScienceHealthy Volunteers1
1CompletedOtherHealthy Volunteers1
1CompletedTreatmentAdult Solid Neoplasm1
1CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection1
1CompletedTreatmentDrug Interactions1
1CompletedTreatmentHealthy Volunteers1
1TerminatedTreatmentCancer, Advanced / Malignant Lymphomas1
1TerminatedTreatmentHealthy Volunteers1
2CompletedTreatmentImpaired Glucose Tolerance (IGT) / Type 2 Diabetes Mellitus1
4RecruitingBasic ScienceType 2 Diabetes Mellitus1
Not AvailableCompletedNot AvailableType 2 Diabetes Mellitus3

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
FormRouteStrength
TabletOral1 g
TabletOral500 mg
TabletOral500 mg/1
Prices
Unit descriptionCostUnit
Tolbutamide 500 mg tablet0.4USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)128.5 °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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Download (9.12 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0006-0190000000-7ff8ebe7a2c8d9b989ec
MS/MS Spectrum - , positiveLC-MS/MSsplash10-05fr-1920000000-defac8a82087405b74df

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzenesulfonamides
Direct Parent
Benzenesulfonamides
Alternative Parents
Tosyl compounds / Benzenesulfonyl compounds / Sulfonylureas / Organosulfonic acids and derivatives / Aminosulfonyl compounds / Propargyl-type 1,3-dipolar organic compounds / Carboximidic acids and derivatives / Organopnictogen compounds / Organooxygen compounds / Organic oxides
show 1 more
Substituents
Benzenesulfonamide / Tosyl compound / Benzenesulfonyl group / Toluene / Sulfonylurea / Organic sulfonic acid or derivatives / Organosulfonic acid or derivatives / Sulfonyl / Aminosulfonyl compound / Carboximidic acid derivative
show 11 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
N-sulfonylurea (CHEBI:27999)

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
Uniprot Name
ATP-binding cassette sub-family C member 8
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...
Gene Name
KCNJ1
Uniprot ID
P48048
Uniprot Name
ATP-sensitive inward rectifier potassium channel 1
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

Details
1. Cytochrome P450 2C9
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 un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
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. 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]
  3. 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. [PubMed:10064574]
  4. 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 . [PubMed:9764927]
  5. 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. [PubMed:9152599]
  6. 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. [PubMed:8822040]
  7. 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]
  8. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
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 un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
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]
  2. 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]
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 im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
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. 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]
  3. 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. [PubMed:10681382]
  4. Canadian Pharmacists Association (2006). Compendium of Pharmaceuticals and Specialties: The Canadian Drug Reference for Health Professionals. Canadian Pharmacists Association. [ISBN:1-894402-22-7]
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 un...
Gene Name
CYP2C18
Uniprot ID
P33260
Uniprot Name
Cytochrome P450 2C18
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]

Carriers

Details
1. Serum albumin
Kind
Protein
Organism
Human
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
  1. 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. [PubMed:19596536]
  2. 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. [PubMed:20435530]
  3. 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. [PubMed:20956006]
  4. 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. [PubMed:20974553]

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
Uniprot Name
Solute carrier family 15 member 1
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 inhibit...
Gene Name
SLCO1A2
Uniprot ID
P46721
Uniprot Name
Solute carrier organic anion transporter family member 1A2
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
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
  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
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
  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
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
  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]

Drug created on June 13, 2005 07:24 / Updated on October 16, 2018 08:34