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Identification
NameGlyburide
Accession NumberDB01016  (APRD00233)
Typesmall molecule
Groupsapproved
Description

Glyburide is an oral antihyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus (NIDDM). It 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. Glyburide has been shown to decrease fasting plasma glucose, postprandial blood glucose and glycosolated hemoglobin (HbA1c) levels (reflective of the last 8-10 weeks of glucose control). Glyburide appears to be completely metabolized, likely in the liver. Although its metabolites exert a small hypoglycemic effect, their contribution to glyburide’s hypoglycemic effect is thought to be clinically unimportant. Glyburide metabolites are excreted in urine and feces in approximately equal proportions. The half-life of glyburide appears to be unaffected in those with a creatinine clearance of greater than 29 ml/min/1.73m2.

Structure
Thumb
Synonyms
SynonymLanguageCode
1-((P-(2-(5-chloro-O-Anisamido)ethyl)phenyl)sulfonyl)-3-cyclohexylureaNot AvailableNot Available
1-(P-(2-(5-chloro-2-Methoxybenzamido)ethyl)benzenesulfonyl)-3-cyclohexylureaNot AvailableNot Available
5-chloro-N-(2-(4-((((Cyclohexylamino)carbonyl)amino)sulfonyl)phenyl)ethyl)-2-methoxybenzamideNot AvailableNot Available
DiabetaNot AvailableNot Available
GlibenclamidaSpanishINN
GlibenclamideNot AvailableINN
GlibenclamidumLatinINN
GlyburideNot AvailableNot Available
GlynaseNot AvailableNot Available
MicronaseNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
DaonilNot Available
DelmideNot Available
DiabetaSanofi-Aventis
EugluconNot Available
GlynaseNot Available
MicronaseNot Available
Novo-GlyburideNovopharm
Semi-DaonilNot Available
Brand mixtures
Brand NameIngredients
BenimetMetformin + Glibenclamide
GlibometMetformin + Glibenclamide
GlucovanceMetformin + Glibenclamide
Categories
CAS number10238-21-8
WeightAverage: 494.004
Monoisotopic: 493.143819418
Chemical FormulaC23H28ClN3O5S
InChI KeyZNNLBTZKUZBEKO-UHFFFAOYSA-N
InChI
InChI=1S/C23H28ClN3O5S/c1-32-21-12-9-17(24)15-20(21)22(28)25-14-13-16-7-10-19(11-8-16)33(30,31)27-23(29)26-18-5-3-2-4-6-18/h7-12,15,18H,2-6,13-14H2,1H3,(H,25,28)(H2,26,27,29)
IUPAC Name
5-chloro-N-[2-(4-{[(cyclohexylcarbamoyl)amino]sulfonyl}phenyl)ethyl]-2-methoxybenzamide
SMILES
COC1=C(C=C(Cl)C=C1)C(=O)NCCC1=CC=C(C=C1)S(=O)(=O)NC(=O)NC1CCCCC1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassBenzenesulfonamides
Direct parentBenzenesulfonamides
Alternative parentsSalicylamides; Phenethylamines; Benzamides; Benzoyl Derivatives; Anisoles; Chlorobenzenes; Sulfonylureas; Alkyl Aryl Ethers; Aryl Chlorides; Sulfonamides; Sulfonyls; Secondary Carboxylic Acid Amides; Enolates; Carboxylic Acids; Polyamines; Organochlorides
Substituentsbenzoyl; anisole; phenol ether; alkyl aryl ether; sulfonylurea; chlorobenzene; aryl halide; aryl chloride; sulfonamide; sulfonic acid derivative; sulfonyl; secondary carboxylic acid amide; carboxamide group; polyamine; enolate; carboxylic acid; carboxylic acid derivative; ether; organochloride; amine; organohalogen; organonitrogen compound
Classification descriptionThis compound belongs to the benzenesulfonamides. These are organic compounds containing a sulfonamide group that is S-linked to a benzene ring.
Pharmacology
IndicationIndicated as an adjunct to diet to lower the blood glucose in patients with NIDDM whose hyperglycemia cannot be satisfactorily controlled by diet alone.
PharmacodynamicsGlyburide, a second-generation sulfonylurea antidiabetic agent, lowers blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. With chronic administration in Type II diabetic patients, the blood glucose lowering effect persists despite a gradual decline in the insulin secretory response to the drug. Extrapancreatic effects may be involved in the mechanism of action of oral sulfonyl-urea hypoglycemic drugs. The combination of glibenclamide and metformin may have a synergistic effect, since both agents act to improve glucose tolerance by different but complementary mechanisms. In addition to its blood glucose lowering actions, glyburide produces a mild diuresis by enhancement of renal free water clearance. Glyburide is twice as potent as the related second-generation agent glipizide.
Mechanism of actionSulfonylureas such as glyburide bind to ATP-sensitive potassium channels on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Depolarization stimulates calcium ion influx through voltage-sensitive calcium channels, raising intracellular concentrations of calcium ions, which induces the secretion, or exocytosis, of insulin.
AbsorptionSignificant absorption within 1 hour and peak plasma levels are reached in 2 to 4 hours. Onset of action occurs within one hour.
Volume of distribution

Steady state Vd=0.125 L/kg; Vd during elimination phase=0.155 L/kg.

Protein bindingUnchanged drug is ~99% bound to serum proteins; 4-trans-hydroxyglyburide is greater than 97% bound to serum proteins. Protein binding is primarily nonionic making glyburide and is less likely to displace or be displaced by drugs that bind via an ionic mechanism.
Metabolism

Primarily hepatic (mainly cytochrome P450 3A4). The major metabolite is the 4-trans-hydroxy derivative. A second metabolite, the 3-cis-hydroxy derivative, also occurs. These metabolites do not contribute clinically significant hypoglycemic action in humans as they are only weakly active; however, retention of 4-trans-hydroxyglyburide may prolong the hypoglycemic effect of the agent in those with severe renal impairment.

SubstrateEnzymesProduct
Glyburide
2-trans-Hydroxycyclohexyl glyburideDetails
Glyburide
4-cis-Hydroxycyclohexyl glyburideDetails
Glyburide
4-trans-Hydroxycyclohexyl glyburideDetails
Glyburide
3-trans-Hydroxycyclohexyl glyburideDetails
Glyburide
3-cis-Hydroxycyclohexyl glyburideDetails
Route of eliminationGlyburide is excreted as metabolites in the bile and urine, approximately 50% by each route. This dual excretory pathway is qualitatively different from that of other sulfonylureas, which are excreted primarily in the urine.
Half life1.4-1.8 hours (unchanged drug only); 10 hours (metabolites included). Duration of effect is 12-24 hours.
Clearance

78 ml/hr/kg in healthy adults. Clearance may be substantially decreased in those with severe renal impairment.

ToxicityOral rat LD50: > 20,000 mg/kg. Oral mouse LD50: 3250 mg/kg.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Glibenclamide Action PathwayDrug actionSMP00460
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9701
Blood Brain Barrier - 0.6707
Caco-2 permeable - 0.6479
P-glycoprotein substrate Non-substrate 0.5109
P-glycoprotein inhibitor I Non-inhibitor 0.7119
P-glycoprotein inhibitor II Non-inhibitor 0.8185
Renal organic cation transporter Non-inhibitor 0.7982
CYP450 2C9 substrate Substrate 0.6488
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Substrate 0.5329
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Inhibitor 0.8948
CYP450 2D6 substrate Inhibitor 0.8932
CYP450 2C19 substrate Non-inhibitor 0.9026
CYP450 3A4 substrate Inhibitor 0.7959
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.8627
Ames test Non AMES toxic 0.6996
Carcinogenicity Non-carcinogens 0.7539
Biodegradation Not ready biodegradable 0.8245
Rat acute toxicity 1.4243 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.7551
hERG inhibition (predictor II) Non-inhibitor 0.8024
Pharmacoeconomics
Manufacturers
  • Sanofi aventis us llc
  • Actavis totowa llc
  • Aurobindo pharma ltd
  • Corepharma llc
  • Teva pharmaceuticals usa inc
  • Dava pharmaceuticals inc
  • Hikma pharmaceuticals
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Pharmacia and upjohn co
Packagers
Dosage forms
FormRouteStrength
TabletOral2.5 mg
TabletOral5 mg
Prices
Unit descriptionCostUnit
Glynase 6 mg tablet2.28USDtablet
Glynase 6 mg prestab2.19USDtablet
Glynase 3 mg tablet1.45USDtablet
Glynase 3 mg prestab1.39USDtablet
Diabeta 5 mg tablet1.36USDtablet
Micronase 5 mg tablet1.36USDtablet
Diabeta 2.5 mg tablet0.91USDtablet
Glynase 1.5 mg tablet0.83USDtablet
Glynase 1.5 mg prestab0.82USDtablet
Micronase 2.5 mg tablet0.8USDtablet
Diabeta 1.25 mg tablet0.5USDtablet
Micronase 1.25 mg tablet0.48USDtablet
Diabeta 5 mg Tablet0.26USDtablet
Diabeta 2.5 mg Tablet0.14USDtablet
Apo-Glyburide 5 mg Tablet0.07USDtablet
Euglucon 5 mg Tablet0.07USDtablet
Mylan-Glybe 5 mg Tablet0.07USDtablet
Novo-Glyburide 5 mg Tablet0.07USDtablet
Nu-Glyburide 5 mg Tablet0.07USDtablet
Pms-Glyburide 5 mg Tablet0.07USDtablet
Ratio-Glyburide 5 mg Tablet0.07USDtablet
Sandoz Glyburide 5 mg Tablet0.07USDtablet
Apo-Glyburide 2.5 mg Tablet0.04USDtablet
Euglucon 2.5 mg Tablet0.04USDtablet
Mylan-Glybe 2.5 mg Tablet0.04USDtablet
Novo-Glyburide 2.5 mg Tablet0.04USDtablet
Nu-Glyburide 2.5 mg Tablet0.04USDtablet
Pms-Glyburide 2.5 mg Tablet0.04USDtablet
Ratio-Glyburide 2.5 mg Tablet0.04USDtablet
Sandoz Glyburide 2.5 mg Tablet0.04USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point169 °CPhysProp
water solubility4 mg/L (at 27 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP4.7Not Available
logS-5.09ADME Research, USCD
Predicted Properties
PropertyValueSource
water solubility2.06e-03 g/lALOGPS
logP3.78ALOGPS
logP3.79ChemAxon
logS-5.4ALOGPS
pKa (strongest acidic)4.32ChemAxon
pKa (strongest basic)-1.2ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count5ChemAxon
hydrogen donor count3ChemAxon
polar surface area113.6ChemAxon
rotatable bond count7ChemAxon
refractivity126.98ChemAxon
polarizability51.75ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Suresh Gidwani, “Solid oral dosage form of metformin and glyburide and the method of preparation thereof.” U.S. Patent US20040175421, issued September 09, 2004.

US20040175421
General Reference
  1. Monami M, Luzzi C, Lamanna C, Chiasserini V, Addante F, Desideri CM, Masotti G, Marchionni N, Mannucci E: Three-year mortality in diabetic patients treated with different combinations of insulin secretagogues and metformin. Diabetes Metab Res Rev. 2006 Nov-Dec;22(6):477-82. Pubmed
External Links
ResourceLink
KEGG DrugD00336
KEGG CompoundC07022
PubChem Compound3488
PubChem Substance46509154
ChemSpider3368
ChEBI5441
ChEMBLCHEMBL472
Therapeutic Targets DatabaseDAP000037
PharmGKBPA449782
IUPHAR2414
Guide to Pharmacology2414
Drug Product Database2248008
RxListhttp://www.rxlist.com/cgi/generic/glybur.htm
WikipediaGlibenclamide
ATC CodesA10BB01
AHFS Codes
  • 68:20.20
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(36.9 KB)
Interactions
Drug Interactions
Drug
AcebutololAcebutolol may decrease symptoms of hypoglycemia and increase the time required for the body to compensate for hypoglycemia.
Acetylsalicylic acidAcetylsalicylic acid increases the effect of the sulfonylurea, glibenclamide.
AtenololThe beta-blocker, atenolol, may decrease symptoms of hypoglycemia.
BetaxololThe beta-blocker, betaxolol, may decrease symptoms of hypoglycemia.
BevantololThe beta-blocker, bevantolol, may decrease symptoms of hypoglycemia.
Bismuth SubsalicylateThe salicylate, bismuth subsalicylate, increases the effect of the sulfonylurea, glibenclamide.
BisoprololThe beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.
BosentanIncreased risk of hepatic toxicity
CarteololThe beta-blocker, carteolol, may decrease symptoms of hypoglycemia.
CarvedilolThe beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
ChloramphenicolChloramphenicol may increase the effect of sulfonylurea, glibenclamide.
ClofibrateClofibrate may increase the effect of sulfonylurea, glibenclamide.
ColesevelamColesevelam may decrease the serum concentration of Glyburide. Glyburide should be administered at least 4 hours before colesevelam to minimize the risk of an interaction.
CyclosporineThe sulfonylurea, glibenclamide, may increase the effect of cyclosporine.
DiazoxideAntagonism.
DicoumarolDicumarol may increase the effect of sulfonylurea, glibenclamide.
EsmololThe beta-blocker, esmolol, may decrease symptoms of hypoglycemia.
GlucosaminePossible hyperglycemia
LabetalolThe beta-blocker, labetalol, may decrease symptoms of hypoglycemia.
Magnesium salicylateThe salicylate, magnesium salicylate, increases the effect of the sulfonylurea, glibenclamide.
MetoprololThe beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.
NadololThe beta-blocker, nadolol, may decrease symptoms of hypoglycemia.
OxprenololThe beta-blocker, oxprenolol, may decrease symptoms of hypoglycemia.
PenbutololThe beta-blocker, penbutolol, may decrease symptoms of hypoglycemia.
PhenylbutazonePhenylbutazone increases the effect of the hypoglycemic agent
PindololThe beta-blocker, pindolol, may decrease symptoms of hypoglycemia.
PractololThe beta-blocker, practolol, may decrease symptoms of hypoglycemia.
PropranololThe beta-blocker, propranolol, may decrease symptoms of hypoglycemia.
RifampicinRifampin may decrease the effect of sulfonylurea, glibenclamide.
Salicylate-sodiumThe salicylate, salicylate-sodium, increases the effect of the sulfonylurea, glibenclamide.
SalsalateThe salicylate, salsalate, increases the effect of the sulfonylurea, glibenclamide.
Somatropin recombinantSomatropin may antagonize the hypoglycemic effect of glibenclamide. Monitor for changes in fasting and postprandial blood sugars.
SotalolThe beta-blocker, sotalol, may decrease symptoms of hypoglycemia.
TimololThe beta-blocker, timolol, may decrease symptoms of hypoglycemia.
Trisalicylate-cholineThe salicylate, trisalicylate-choline, increases the effect of the sulfonylurea, glibenclamide.
Food Interactions
  • Avoid alcohol.
  • Take 30-60 minutes before breakfast.

Targets

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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: modulator

Components

Name UniProt ID Details
ATP-binding cassette sub-family C member 8 Q09428 Details

References:

  1. Dabrowski M, Ashcroft FM, Ashfield R, Lebrun P, Pirotte B, Egebjerg J, Bondo Hansen J, Wahl P: The novel diazoxide analog 3-isopropylamino-7-methoxy-4H-1,2,4-benzothiadiazine 1,1-dioxide is a selective Kir6.2/SUR1 channel opener. Diabetes. 2002 Jun;51(6):1896-906. Pubmed
  2. Hambrock A, Preisig-Muller R, Russ U, Piehl A, Hanley PJ, Ray J, Daut J, Quast U, Derst C: Four novel splice variants of sulfonylurea receptor 1. Am J Physiol Cell Physiol. 2002 Aug;283(2):C587-98. Pubmed
  3. Hambrock A, Loffler-Walz C, Quast U: Glibenclamide binding to sulphonylurea receptor subtypes: dependence on adenine nucleotides. Br J Pharmacol. 2002 Aug;136(7):995-1004. Pubmed
  4. Nielsen FE, Bodvarsdottir TB, Worsaae A, MacKay P, Stidsen CE, Boonen HC, Pridal L, Arkhammar PO, Wahl P, Ynddal L, Junager F, Dragsted N, Tagmose TM, Mogensen JP, Koch A, Treppendahl SP, Hansen JB: 6-Chloro-3-alkylamino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide derivatives potently and selectively activate ATP sensitive potassium channels of pancreatic beta-cells. J Med Chem. 2002 Sep 12;45(19):4171-87. Pubmed
  5. Babenko AP, Bryan J: SUR-dependent modulation of KATP channels by an N-terminal KIR6.2 peptide. Defining intersubunit gating interactions. J Biol Chem. 2002 Nov 15;277(46):43997-4004. Epub 2002 Sep 3. Pubmed
  6. Ueda K, Komine J, Matsuo M, Seino S, Amachi T: Cooperative binding of ATP and MgADP in the sulfonylurea receptor is modulated by glibenclamide. Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1268-72. Pubmed
  7. Serrano-Martin X, Payares G, Mendoza-Leon A: Glibenclamide, a blocker of K+(ATP) channels, shows antileishmanial activity in experimental murine cutaneous leishmaniasis. Antimicrob Agents Chemother. 2006 Dec;50(12):4214-6. Epub 2006 Oct 2. Pubmed
  8. Hambrock A, Loffler-Walz C, Quast U: Glibenclamide binding to sulphonylurea receptor subtypes: dependence on adenine nucleotides. Br J Pharmacol. 2002 Aug;136(7):995-1004. Pubmed

2. ATP-sensitive inward rectifier potassium channel 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
ATP-sensitive inward rectifier potassium channel 1 P48048 Details

References:

  1. Pondugula SR, Raveendran NN, Ergonul Z, Deng Y, Chen J, Sanneman JD, Palmer LG, Marcus DC: Glucocorticoid regulation of genes in the amiloride-sensitive sodium transport pathway by semicircular canal duct epithelium of neonatal rat. Physiol Genomics. 2006 Jan 12;24(2):114-23. Epub 2005 Nov 1. Pubmed
  2. Lu M, Leng Q, Egan ME, Caplan MJ, Boulpaep EL, Giebisch GH, Hebert SC: CFTR is required for PKA-regulated ATP sensitivity of Kir1.1 potassium channels in mouse kidney. J Clin Invest. 2006 Mar;116(3):797-807. Epub 2006 Feb 9. Pubmed

3. G protein-activated inward rectifier potassium channel 4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
G protein-activated inward rectifier potassium channel 4 P48544 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

4. ATP-binding cassette sub-family C member 9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: modulator

Components

Name UniProt ID Details
ATP-binding cassette sub-family C member 9 O60706 Details

References:

  1. Hambrock A, Loffler-Walz C, Quast U: Glibenclamide binding to sulphonylurea receptor subtypes: dependence on adenine nucleotides. Br J Pharmacol. 2002 Aug;136(7):995-1004. Pubmed
  2. Rainbow RD, James M, Hudman D, Al Johi M, Singh H, Watson PJ, Ashmole I, Davies NW, Lodwick D, Norman RI: Proximal C-terminal domain of sulphonylurea receptor 2A interacts with pore-forming Kir6 subunits in KATP channels. Biochem J. 2004 Apr 1;379(Pt 1):173-81. Pubmed
  3. Felsch H, Lange U, Hambrock A, Loffler-Walz C, Russ U, Carroll WA, Gopalakrishnan M, Quast U: Interaction of a novel dihydropyridine K+ channel opener, A-312110, with recombinant sulphonylurea receptors and KATP channels: comparison with the cyanoguanidine P1075. Br J Pharmacol. 2004 Apr;141(7):1098-105. Epub 2004 Mar 15. Pubmed
  4. Zhao JL, Yang YJ, You SJ, Jing ZC, Wu YJ, Cheng JL, Gao RL: Pretreatment with fosinopril or valsartan reduces myocardial no-reflow after acute myocardial infarction and reperfusion. Coron Artery Dis. 2006 Aug;17(5):463-9. Pubmed
  5. Wang YH, Zheng HY, Qin NL, Yu SB, Liu SY: Involvement of ATP-sensitive potassium channels in proliferation and differentiation of rat preadipocytes. Sheng Li Xue Bao. 2007 Feb 25;59(1):8-12. Pubmed
  6. Hambrock A, Loffler-Walz C, Quast U: Glibenclamide binding to sulphonylurea receptor subtypes: dependence on adenine nucleotides. Br J Pharmacol. 2002 Aug;136(7):995-1004. Pubmed

5. Bile salt export pump

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Bile salt export pump O95342 Details

References:

  1. Byrne JA, Strautnieks SS, Mieli-Vergani G, Higgins CF, Linton KJ, Thompson RJ: The human bile salt export pump: characterization of substrate specificity and identification of inhibitors. Gastroenterology. 2002 Nov;123(5):1649-58. Pubmed
  2. Kemp DC, Brouwer KL: Viability assessment in sandwich-cultured rat hepatocytes after xenobiotic exposure. Toxicol In Vitro. 2004 Dec;18(6):869-77. Pubmed
  3. Horikawa M, Kato Y, Tyson CA, Sugiyama Y: Potential cholestatic activity of various therapeutic agents assessed by bile canalicular membrane vesicles isolated from rats and humans. Drug Metab Pharmacokinet. 2003;18(1):16-22. Pubmed

6. ATP-binding cassette sub-family A member 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
ATP-binding cassette sub-family A member 1 O95477 Details

References:

  1. Reddy ST, Hama S, Ng C, Grijalva V, Navab M, Fogelman AM: ATP-binding cassette transporter 1 participates in LDL oxidation by artery wall cells. Arterioscler Thromb Vasc Biol. 2002 Nov 1;22(11):1877-83. Pubmed
  2. Muhl H, Hofler S, Pfeilschifter J: Inhibition of lipopolysaccharide/ATP-induced release of interleukin-18 by KN-62 and glyburide. Eur J Pharmacol. 2003 Dec 15;482(1-3):325-8. Pubmed
  3. Agassandian M, Mathur SN, Zhou J, Field FJ, Mallampalli RK: Oxysterols trigger ABCA1-mediated basolateral surfactant efflux. Am J Respir Cell Mol Biol. 2004 Aug;31(2):227-33. Epub 2004 Mar 23. Pubmed
  4. Nieland TJ, Chroni A, Fitzgerald ML, Maliga Z, Zannis VI, Kirchhausen T, Krieger M: Cross-inhibition of SR-BI- and ABCA1-mediated cholesterol transport by the small molecules BLT-4 and glyburide. J Lipid Res. 2004 Jul;45(7):1256-65. Epub 2004 Apr 21. Pubmed
  5. Alder-Baerens N, Muller P, Pohl A, Korte T, Hamon Y, Chimini G, Pomorski T, Herrmann A: Headgroup-specific exposure of phospholipids in ABCA1-expressing cells. J Biol Chem. 2005 Jul 15;280(28):26321-9. Epub 2005 May 19. Pubmed
  6. Lamkanfi M, Mueller JL, Vitari AC, Misaghi S, Fedorova A, Deshayes K, Lee WP, Hoffman HM, Dixit VM: Glyburide inhibits the Cryopyrin/Nalp3 inflammasome. J Cell Biol. 2009 Oct 5;187(1):61-70. doi: 10.1083/jcb.200903124. Pubmed

7. Cystic fibrosis transmembrane conductance regulator

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Cystic fibrosis transmembrane conductance regulator P13569 Details

References:

  1. Reddy MM, Quinton PM: Effect of anion transport blockers on CFTR in the human sweat duct. J Membr Biol. 2002 Sep 1;189(1):15-25. Pubmed
  2. Jiang J, Song Y, Bai C, Koller BH, Matthay MA, Verkman AS: Pleural surface fluorescence measurement of Na+ and Cl- transport across the air space-capillary barrier. J Appl Physiol. 2003 Jan;94(1):343-52. Epub 2002 Aug 30. Pubmed
  3. Zhou Z, Hu S, Hwang TC: Probing an open CFTR pore with organic anion blockers. J Gen Physiol. 2002 Nov;120(5):647-62. Pubmed
  4. Larsen EH, Amstrup J, Willumsen NJ: Beta-adrenergic receptors couple to CFTR chloride channels of intercalated mitochondria-rich cells in the heterocellular toad skin epithelium. Biochim Biophys Acta. 2003 Dec 30;1618(2):140-52. Pubmed
  5. Lee SY, Lee CO: Inhibition of Na+-K+ pump and L-type Ca2+ channel by glibenclamide in Guinea pig ventricular myocytes. J Pharmacol Exp Ther. 2005 Jan;312(1):61-8. Epub 2004 Sep 13. Pubmed

8. ATP-sensitive inward rectifier potassium channel 11

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: modulator

Components

Name UniProt ID Details
ATP-sensitive inward rectifier potassium channel 11 Q14654 Details

References:

  1. Hambrock A, Loffler-Walz C, Quast U: Glibenclamide binding to sulphonylurea receptor subtypes: dependence on adenine nucleotides. Br J Pharmacol. 2002 Aug;136(7):995-1004. Pubmed
  2. Nielsen FE, Bodvarsdottir TB, Worsaae A, MacKay P, Stidsen CE, Boonen HC, Pridal L, Arkhammar PO, Wahl P, Ynddal L, Junager F, Dragsted N, Tagmose TM, Mogensen JP, Koch A, Treppendahl SP, Hansen JB: 6-Chloro-3-alkylamino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide derivatives potently and selectively activate ATP sensitive potassium channels of pancreatic beta-cells. J Med Chem. 2002 Sep 12;45(19):4171-87. Pubmed
  3. Gojkovic-Bukarica L, Hambrock A, Loffler-Walz C, Quast U, Russ U: Mg2+ sensitizes KATP channels to inhibition by DIDS: dependence on the sulphonylurea receptor subunit. Br J Pharmacol. 2002 Oct;137(4):429-40. Pubmed
  4. Ball AJ, McCluskey JT, Flatt PR, McClenaghan NH: Chronic exposure to tolbutamide and glibenclamide impairs insulin secretion but not transcription of K(ATP) channel components. Pharmacol Res. 2004 Jul;50(1):41-6. Pubmed
  5. Lim JG, Lee HY, Yun JE, Kim SP, Park JW, Suh SI, Jang BC, Cho CH, Bae JH, Kim SS, Han J, Park MJ, Song DK: Taurine block of cloned ATP-sensitive K+ channels with different sulfonylurea receptor subunits expressed in Xenopus laevis oocytes. Biochem Pharmacol. 2004 Sep 1;68(5):901-10. Pubmed

9. Mitochondrial ATP-sensitive potassium channel

Kind: protein group

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
ATP-sensitive inward rectifier potassium channel 11 Q14654 Details
ATP-sensitive inward rectifier potassium channel 8 Q15842 Details

References:

  1. Jaburek M, Yarov-Yarovoy V, Paucek P, Garlid KD: State-dependent inhibition of the mitochondrial KATP channel by glyburide and 5-hydroxydecanoate. J Biol Chem. 1998 May 29;273(22):13578-82. Pubmed

10. Carnitine O-palmitoyltransferase 1, liver isoform

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Carnitine O-palmitoyltransferase 1, liver isoform P50416 Details

References:

  1. Patel TB: Effect of sulfonylureas on hepatic fatty acid oxidation. Am J Physiol. 1986 Aug;251(2 Pt 1):E241-6. Pubmed
  2. Cook GA: The hypoglycemic sulfonylureas glyburide and tolbutamide inhibit fatty acid oxidation by inhibiting carnitine palmitoyltransferase. J Biol Chem. 1987 Apr 15;262(11):4968-72. Pubmed

Enzymes

1. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

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
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. 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. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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
  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. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

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
  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. Epub 2009 Nov 24. Pubmed

Carriers

1. Serum albumin

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Serum albumin P02768 Details

References:

  1. Crooks MJ, Brown KF: The binding of sulphonylureas to serum albumin. J Pharm Pharmacol. 1974 May;26(5):304-11. Pubmed
  2. Hsu PL, Ma JK, Luzzi LA: Interactions of sulfonylureas with plasma proteins. J Pharm Sci. 1974 Apr;63(4):570-3. Pubmed
  3. Brown KF, Crooks MJ: Displacement of tolbutamide, glibencalmide and chlorpropamide from serum albumin by anionic drugs. Biochem Pharmacol. 1976 May 15;25(10):1175-8. Pubmed

Transporters

1. Canalicular multispecific organic anion transporter 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Canalicular multispecific organic anion transporter 2 O15438 Details

References:

  1. Gedeon C, Behravan J, Koren G, Piquette-Miller M: Transport of glyburide by placental ABC transporters: implications in fetal drug exposure. Placenta. 2006 Nov-Dec;27(11-12):1096-102. Epub 2006 Feb 3. Pubmed

2. Bile salt export pump

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Bile salt export pump O95342 Details

References:

  1. Byrne JA, Strautnieks SS, Mieli-Vergani G, Higgins CF, Linton KJ, Thompson RJ: The human bile salt export pump: characterization of substrate specificity and identification of inhibitors. Gastroenterology. 2002 Nov;123(5):1649-58. Pubmed
  2. Wang EJ, Casciano CN, Clement RP, Johnson WW: Fluorescent substrates of sister-P-glycoprotein (BSEP) evaluated as markers of active transport and inhibition: evidence for contingent unequal binding sites. Pharm Res. 2003 Apr;20(4):537-44. Pubmed
  3. Noe J, Hagenbuch B, Meier PJ, St-Pierre MV: Characterization of the mouse bile salt export pump overexpressed in the baculovirus system. Hepatology. 2001 May;33(5):1223-31. Pubmed
  4. Funk C, Pantze M, Jehle L, Ponelle C, Scheuermann G, Lazendic M, Gasser R: Troglitazone-induced intrahepatic cholestasis by an interference with the hepatobiliary export of bile acids in male and female rats. Correlation with the gender difference in troglitazone sulfate formation and the inhibition of the canalicular bile salt export pump (Bsep) by troglitazone and troglitazone sulfate. Toxicology. 2001 Oct 5;167(1):83-98. Pubmed
  5. Stieger B, Fattinger K, Madon J, Kullak-Ublick GA, Meier PJ: Drug- and estrogen-induced cholestasis through inhibition of the hepatocellular bile salt export pump (Bsep) of rat liver. Gastroenterology. 2000 Feb;118(2):422-30. Pubmed

3. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. Golstein PE, Boom A, van Geffel J, Jacobs P, Masereel B, Beauwens R: P-glycoprotein inhibition by glibenclamide and related compounds. Pflugers Arch. 1999 Apr;437(5):652-60. Pubmed

4. Multidrug resistance-associated protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance-associated protein 1 P33527 Details

References:

  1. Payen L, Delugin L, Courtois A, Trinquart Y, Guillouzo A, Fardel O: The sulphonylurea glibenclamide inhibits multidrug resistance protein (MRP1) activity in human lung cancer cells. Br J Pharmacol. 2001 Feb;132(3):778-84. Pubmed
  2. Gedeon C, Behravan J, Koren G, Piquette-Miller M: Transport of glyburide by placental ABC transporters: implications in fetal drug exposure. Placenta. 2006 Nov-Dec;27(11-12):1096-102. Epub 2006 Feb 3. Pubmed

5. Solute carrier family 15 member 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 15 member 1 P46059 Details

References:

  1. Sawada K, Terada T, Saito H, Hashimoto Y, Inui K: Effects of glibenclamide on glycylsarcosine transport by the rat peptide transporters PEPT1 and PEPT2. Br J Pharmacol. 1999 Nov;128(6):1159-64. Pubmed

6. Solute carrier organic anion transporter family member 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 1A2 P46721 Details

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

7. Solute carrier family 15 member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 15 member 2 Q16348 Details

References:

  1. Sawada K, Terada T, Saito H, Hashimoto Y, Inui K: Effects of glibenclamide on glycylsarcosine transport by the rat peptide transporters PEPT1 and PEPT2. Br J Pharmacol. 1999 Nov;128(6):1159-64. Pubmed

8. Solute carrier family 22 member 6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 6 Q4U2R8 Details

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

9. Canalicular multispecific organic anion transporter 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Canalicular multispecific organic anion transporter 1 Q92887 Details

References:

  1. Gedeon C, Behravan J, Koren G, Piquette-Miller M: Transport of glyburide by placental ABC transporters: implications in fetal drug exposure. Placenta. 2006 Nov-Dec;27(11-12):1096-102. Epub 2006 Feb 3. Pubmed
  2. Payen L, Delugin L, Courtois A, Trinquart Y, Guillouzo A, Fardel O: The sulphonylurea glibenclamide inhibits multidrug resistance protein (MRP1) activity in human lung cancer cells. Br J Pharmacol. 2001 Feb;132(3):778-84. Pubmed

10. ATP-binding cassette sub-family G member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
ATP-binding cassette sub-family G member 2 Q9UNQ0 Details

References:

  1. Gedeon C, Behravan J, Koren G, Piquette-Miller M: Transport of glyburide by placental ABC transporters: implications in fetal drug exposure. Placenta. 2006 Nov-Dec;27(11-12):1096-102. Epub 2006 Feb 3. Pubmed
  2. Pollex EK, Anger G, Hutson J, Koren G, Piquette-Miller M: Breast cancer resistance protein (BCRP)-mediated glyburide transport: effect of the C421A/Q141K BCRP single-nucleotide polymorphism. Drug Metab Dispos. 2010 May;38(5):740-4. Epub 2010 Feb 16. Pubmed

11. Solute carrier family 22 member 7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 7 Q9Y694 Details

References:

  1. Morita N, Kusuhara H, Sekine T, Endou H, Sugiyama Y: Functional characterization of rat organic anion transporter 2 in LLC-PK1 cells. J Pharmacol Exp Ther. 2001 Sep;298(3):1179-84. Pubmed

12. Solute carrier organic anion transporter family member 2B1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 2B1 O94956 Details

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

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:13