GLYBURIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C23H28ClN3O5S
Molecular Weight	494.004
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=C(C=C(Cl)C=C1)C(=O)NCCC2=CC=C(C=C2)S(=O)(=O)NC(=O)NC3CCCCC3

InChI

InChIKey=ZNNLBTZKUZBEKO-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB01016
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/017532Orig1s034lbl.pdf

Glyburide, 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. Sulfonylureas 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. Glyburide is indicated as an adjunct to diet to lower the blood glucose in patients with NIDDM whose hyperglycemia cannot be satisfactorily controlled by diet alone. Glyburide is available as a generic, is manufactured by many pharmaceutical companies and is sold in doses of 1.25, 2.5 and 5 mg under many brand names including Gliben-J, Daonil, Diabeta, Euglucon, Gilemal, Glidanil, Glybovin, Glynase, Maninil, Micronase and Semi-Daonil. It is also available in a fixed-dose combination drug with metformin that is sold under various trade names, e.g. Bagomet Plus, Benimet, Glibomet, Gluconorm, Glucored, Glucovance, Metglib and many others.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Sulfonylurea receptor 1 5 Target ID: CHEMBL2071 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11716850	Agonist 2678	7.1 nM [IC50]
Sulfonylurea receptor 2 9 Target ID: CHEMBL3244 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15294453	Modulator 828	5.2 nM [IC50]
Cytochrome P450 2C9 50 Target ID: CHEMBL3397 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12920163	Inhibitor 8297	2.4 µM [Ki]
Cytochrome P450 3A4 127 Target ID: CHEMBL340 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12920163	Inhibitor 8297	42.5 µM [Ki]
Acyl coenzyme A:cholesterol acyltransferase 15 Target ID: CHEMBL2265 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11032738	Inhibitor 8297	20.0 µM [IC50]
Sulfonylurea receptor 1, Kir6.2 13 Target ID: CHEMBL2096972 Sources: http://www.genome.jp/dbget-bin/www_bget?D00336	Agonist 2678	4.3 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Type 2 diabetes mellitus 259 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/017532Orig1s034lbl.pdf	Primary		Approved 8429	Diaßeta Approved Use Diaßeta is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Launch Date 4.52131193E11

C_max

Value	Dose	Co-administered	Analyte	Population
91.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11406737/	1.75 mg single, oral dose: 1.75 mg route of administration: Oral experiment type: SINGLE co-administered:		GLYBURIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
323.9 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11406737/	1.75 mg single, oral dose: 1.75 mg route of administration: Oral experiment type: SINGLE co-administered:		GLYBURIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11406737/	1.75 mg single, oral dose: 1.75 mg route of administration: Oral experiment type: SINGLE co-administered:		GLYBURIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
40 mg 1 times / day multiple, oral Highest studied dose Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/4927607/	unhealthy, adult n = 23 Health Status: unhealthy Condition: diabetes Age Group: adult Sex: M+F Population Size: 23 Sources: https://pubmed.ncbi.nlm.nih.gov/4927607/	Sources: https://pubmed.ncbi.nlm.nih.gov/4927607/
5 mg 1 times / day multiple, oral (median) Recommended Dose: 5 mg, 1 times / day Route: oral Route: multiple Dose: 5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16021069/	unhealthy, mean age 32.8 years n = 236 Health Status: unhealthy Condition: gestational diabetes mellitus Age Group: mean age 32.8 years Sex: F Population Size: 236 Sources: https://pubmed.ncbi.nlm.nih.gov/16021069/	Disc. AE: Hypoglycemia... AEs leading to discontinuation/dose reduction: Hypoglycemia (5%) Sources: https://pubmed.ncbi.nlm.nih.gov/16021069/
2.5 mg 1 times / day steady, oral (starting) Dose: 2.5 mg, 1 times / day Route: oral Route: steady Dose: 2.5 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00744965	unhealthy\|pregnant n = 189 Health Status: unhealthy\|pregnant Condition: Mild Gestational Diabetes Sex: F Population Size: 189 Sources: https://clinicaltrials.gov/ct2/show/NCT00744965	Other AEs: Facial swelling... Other AEs: Facial swelling (serious, 1 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT00744965

AEs

AE	Significance	Dose	Population
Hypoglycemia	5% Disc. AE	5 mg 1 times / day multiple, oral (median) Recommended Dose: 5 mg, 1 times / day Route: oral Route: multiple Dose: 5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16021069/	unhealthy, mean age 32.8 years n = 236 Health Status: unhealthy Condition: gestational diabetes mellitus Age Group: mean age 32.8 years Sex: F Population Size: 236 Sources: https://pubmed.ncbi.nlm.nih.gov/16021069/
Facial swelling	serious, 1 patient	2.5 mg 1 times / day steady, oral (starting) Dose: 2.5 mg, 1 times / day Route: oral Route: steady Dose: 2.5 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00744965	unhealthy\|pregnant n = 189 Health Status: unhealthy\|pregnant Condition: Mild Gestational Diabetes Sex: F Population Size: 189 Sources: https://clinicaltrials.gov/ct2/show/NCT00744965

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	substrate 1037 inhibitor 1767	substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
MRP5 22 BSEP 402 OCT1 512 OATP1B1 788	CYP2C19 991 OATP2B1 104

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12920163/ Page: 2.0	weak [IC50 90 uM]	weak (co-administration study) Comment: Glyburide reduced the mean AUCτ of bosentan and the phenol, hydroxy, and hydroxy-phenol metabolites 29%, 26%, 25%, and 22% (all P < .05), respectively Sources: https://pubmed.ncbi.nlm.nih.gov/12920163/ Page: 2.0
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12920163/ Page: 2.0	yes [IC50 11.3 uM]	weak (co-administration study) Comment: Glyburide reduced the mean AUCτ of bosentan and the phenol, hydroxy, and hydroxy-phenol metabolites 29%, 26%, 25%, and 22% (all P < .05), respectively Sources: https://pubmed.ncbi.nlm.nih.gov/12920163/ Page: 2.0
MRP5 48	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/15897250/	yes [IC50 15 uM]
BSEP 403	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19520776/	yes [IC50 18.8 uM]
OCT1 543	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20567254/	yes [IC50 199 uM]
OATP1B1 803	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16595711/	yes [Ki 0.75 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/017532s038lbl.pdf#page=5; https://pubmed.ncbi.nlm.nih.gov/9069698/ Page: 5.0	major	yes (co-administration study) Comment: Coadministration with rifampin (inducer) increased blood sugar levels in 17 of 29 patients (595) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/017532s038lbl.pdf#page=5; https://pubmed.ncbi.nlm.nih.gov/9069698/ Page: 5.0
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11956508/	minor
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/017532s038lbl.pdf#page=5; https://pubmed.ncbi.nlm.nih.gov/9069698/ Page: 5.0	minor	yes (co-administration study) Comment: Coadministration with rifampin (inducer) increased blood sugar levels in 17 of 29 patients (595) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/017532s038lbl.pdf#page=5; https://pubmed.ncbi.nlm.nih.gov/9069698/ Page: 5.0
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11956508/	no
OATP2B1 104	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15640378/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:5441	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:5441
ChemicalBook	CB1737679	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1737679
MolPort	MolPort-000-784-850	https://www.molport.com/shop/molecule-link/MolPort-000-784-850
Selleck Chemicals	Glyburide(Diabeta)	http://www.selleckchem.com/products/Glyburide(Diabeta).html
ZINC	ZINC000000537805	http://zinc15.docking.org/substances/ZINC000000537805
eMolecules	27520402	https://www.emolecules.com/cgi-bin/more?vid=27520402
eMolecules	538570	https://www.emolecules.com/cgi-bin/more?vid=538570

PubMed

Title	Date	PubMed
Drug interaction: omeprazole and phenprocoumon.	2001	11313000
The endothelin antagonist bosentan inhibits the canalicular bile salt export pump: a potential mechanism for hepatic adverse reactions.	2001 Apr	11309550
Levosimendan increases diastolic coronary flow in isolated guinea-pig heart by opening ATP-sensitive potassium channels.	2001 Apr	11300649
Differential effects of short and long duration insulinotropic agents on meal-related glucose excursions.	2001 Apr	11298729
Effects of bezafibrate on insulin sensitivity and insulin secretion in non-obese Japanese type 2 diabetic patients.	2001 Apr	11288046
Troglitazone prevents the rise in visceral adiposity and improves fatty liver associated with sulfonylurea therapy--a randomized controlled trial.	2001 Apr	11288035
Protein kinase C isoform-dependent modulation of ATP-sensitive K+ channels during reoxygenation in guinea-pig ventricular myocytes.	2001 Apr 1	11283232
Flow-induced dilation of human coronary arterioles: important role of Ca(2+)-activated K(+) channels.	2001 Apr 17	11306529
The Arabidopsis thaliana ABC transporter AtMRP5 controls root development and stomata movement.	2001 Apr 17	11296221
Effects of phosphodiesterase inhibitors on hypoxic pulmonary vasoconstriction. Influence of K(+) channels and nitric oxide.	2001 Apr 6	11301069
Nitrooxy alkyl apovincaminate activates K+ currents in rat neocortical neurons.	2001 Feb	11286393
Changes in cell volume induced by activation of the cyclic amp-dependent chloride channel in guinea-pig cardiac myocytes.	2001 Feb	11281994
Do ATP and UTP involve cGMP in positive inotropism on rat atria?	2001 Feb	11239839
ATP-sensitive potassium channel openers may mimic the effects of hypoxic preconditioning on the coronary artery.	2001 Feb	11235721
Effects of potassium channel opener aprikalim on the receptor-mediated vasoconstriction in the human internal mammary artery.	2001 Feb	11235720
Differential inhibition of functional dilation of small arterioles by indomethacin and glibenclamide.	2001 Feb	11230341
[Enhancing effect of switching iontophoresis on transdermal absorption of glibenclamide].	2001 Feb	11218730
Effects of K+ channel openers on I K(ATP) of human atrial myocytes at physiological temperatures.	2001 Feb	11218064
[Gestational diabetes: an alternative to insulin therapy?].	2001 Feb 3	11229308
The role of oxygen-derived free radicals in augmented relaxations to levcromakalim in the aorta from hypertensive rats.	2001 Jan	11243571
Mitochondrial ATP dependent potassium channels mediate non-ischemic preconditioning by tachycardia in dogs.	2001 Jan	11216857
Post-prandial hyperglycemia and its implications in pregnancy and lipid abnormalities.	2001 Jan 25	11235600
Formulation, characterization, and in vitro release of glyburide from proliposomal beads.	2001 Jan-Mar	11280440
ATP-binding cassette transporter A1 (ABCA1) functions as a cholesterol efflux regulatory protein.	2001 Jun 29	11309399
Hypoglycemic and antihyperglycemic activity of Syzygium alternifolium (Wt.) Walp. seed extracts in normal and diabetic rats.	2001 Mar	11315761
Hemodynamic, metabolic and hormonal responses to oral glibenclamide in patients with cirrhosis receiving glucose.	2001 Mar	11305519
The role of K+ATP channels in the control of pre- and post-ischemic left ventricular developed pressure in septic rat hearts.	2001 Mar	11294597
Improvement of glycemic control by 1 year of insulin therapy leads to a sustained decrease in sE-selectin concentrations in type 2 diabetes.	2001 Mar	11289483
Inhibitory effects of nicorandil on rat mesangial cell proliferation via the protein kinase G pathway.	2001 Mar	11287762
HNS-32, a novel azulene-1-carboxamidine derivative, inhibits nifedipine-sensitive and -insensitive contraction of the isolated rabbit aorta.	2001 Mar	11284450
Effect of Aloe vera leaves on blood glucose level in type I and type II diabetic rat models.	2001 Mar	11268118
The mechanism of gentisic acid-induced relaxation of the guinea pig isolated trachea: the role of potassium channels and vasoactive intestinal peptide receptors.	2001 Mar	11262590
Mechanism of CGRP-induced relaxation in rat intramural coronary arteries.	2001 Mar	11250874
Investigation of mechanisms that mediate reactive hyperaemia in guinea-pig hearts: role of K(ATP) channels, adenosine, nitric oxide and prostaglandins.	2001 Mar	11250871
Functional characterisation of human TASK-3, an acid-sensitive two-pore domain potassium channel.	2001 Mar	11249964
Characterization of secretory and morphologic properties of primary cultured endocrine cells from porcine pancreata.	2001 Mar	11249067
Ascorbic acid-induced modulation of venous tone in humans.	2001 Mar	11244023
Concentration of the complement activation product, acylation-stimulating protein, is related to C-reactive protein in patients with type 2 diabetes.	2001 Mar	11230779
Effects of KRN2391 on ionic currents in rabbit femoral arterial myocytes.	2001 Mar	11226147
Regulation of an outwardly rectifying chloride conductance in renal epithelial cells by external and internal calcium.	2001 Mar 1	11284203
Gramicidin-perforated patch analysis on HCO3- secretion through a forskolin-activated anion channel in rat parotid intralobular duct cells.	2001 Mar 1	11284200
Profile of moxifloxacin drug interactions.	2001 Mar 15	11249829
Nicorandil--induced ATP release in endothelial cells of rat caudal artery is associated with increase in intracellular Ca(2+).	2001 Mar 30	11290367
Functional roles of cardiac and vascular ATP-sensitive potassium channels clarified by Kir6.2-knockout mice.	2001 Mar 30	11282890
Role of K+ channels in N-acetylprocainamide-induced relaxation of bovine tracheal smooth muscle.	2001 Mar 9	11245854
Characteristics of pancreatic beta-cell secretion in Type 2 diabetic patients treated with gliclazide and glibenclamide.	2001 May	11311964
Diamidine compounds: selective uptake and targeting in Plasmodium falciparum.	2001 May	11306715
Phospholipids as modulators of K(ATP) channels: distinct mechanisms for control of sensitivity to sulphonylureas, K(+) channel openers, and ATP.	2001 May	11306691
Characterization of PGE2 receptors in fetal and newborn lamb ductus arteriosus.	2001 May	11299240
Low levels of K(ATP) channel activation decrease excitability and contractility of urinary bladder.	2001 May	11294764

Patents

Sample Use Guides

In Vivo Use Guide

The usual starting dose is 2.5 to 5 mg daily, administered with breakfast or the first main meal. Those patients who may be more sensitive to hypoglycemic drugs should be started at 1.25 mg daily. The usual maintenance dose is in the range of 1.25 to 20 mg daily, which may be given as a single dose or in divided doses.

Route of Administration: Oral

In Vitro Use Guide

Inhibition of ABCA1 by glibenclamide (Glyburide) has been reported to occur in the concentration range of 100 to 1,000 uM

Name

Type

Language

GLYBURIDE

Official Name

English

U-26452

Code

English

CIRARA

Brand Name

English

HB-419

Code

English

GLIBENCLAMIDE [EP MONOGRAPH]

Common Name

English

GLYBURIDE [WHO-IP]

Common Name

English

GLYBURIDE [MI]

Common Name

English

GLYBENCLAMIDE

Common Name

English

U-26,45

Code

English

GLYBURIDE [USP MONOGRAPH]

Common Name

English

GLUCOVANCE COMPONENT GLYBURIDE

Common Name

English

GLYBURIDE COMPONENT OF GLUCOVANCE

Common Name

English

MICRONASE

Brand Name

English

HB 419

Code

English

GLYBURIDE [USAN]

Common Name

English

NSC-759618

Code

English

GLIBENCLAMIDUM [WHO-IP LATIN]

Common Name

English

GLIBENCLAMIDE

Official Name

English

GLYBURIDE [VANDF]

Common Name

English

BENZAMIDE, 5-CHLORO-N-(2-(4-((((CYCLOHEXYLAMINO)CARBONYL)AMINO)SULFONYL)PHENYL)ETHYL)-2-METHOXY-

Systematic Name

English

GLIBENCLAMIDE [MART.]

Common Name

English

GLIBENCLAMIDE [WHO-IP]

Common Name

English

U-26,452

Code

English

GLYBURIDE [USP-RS]

Common Name

English

glibenclamide [INN]

Common Name

English

Glibenclamide [WHO-DD]

Common Name

English

GLYNASE

Brand Name

English

GLIBENCLAMIDE [JAN]

Common Name

English

DIABETA

Brand Name

English

1-((P-(2-(5-CHLORO-O-ANISAMIDO)ETHYL)PHENYL)SULFONYL)-3-CYCLOHEXYLUREA

Common Name

English

GLYBURIDE [ORANGE BOOK]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000008054