U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C23H28ClN3O5S
Molecular Weight 494.0054
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of GLYBURIDE

SMILES

COc1ccc(cc1C(=NCCc2ccc(cc2)S(=O)(=O)NC(=NC3CCCCC3)O)O)Cl

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
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

Curator's Comment:: Weak penetration in rodents was shown. Glyburide reaches the central nervous system when given systemically, is rapidly removed across the BBB when given intracranioventricularly, and any Glyburide that does enter (and is below detection limit) is insufficient to influence neuronal function

Originator

Sources: Pharmaceutical Manufacturing Encyclopedia retrieved from William Andrew Publishing, p.1783
Curator's Comment:: Introduced as Daonil by Hoechst, Germany

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
91.1 ng/mL
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

AUC

ValueDoseCo-administeredAnalytePopulation
323.9 ng × h/mL
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2 h
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

Doses

DosePopulationAdverse 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:
unhealthy, adult
n = 23
Health Status: unhealthy
Condition: diabetes
Age Group: adult
Sex: M+F
Population Size: 23
Sources:
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:
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:
Disc. AE: Hypoglycemia...
AEs leading to
discontinuation/dose reduction:
Hypoglycemia (5%)
Sources:
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:
unhealthy|pregnant
n = 189
Health Status: unhealthy|pregnant
Condition: Mild Gestational Diabetes
Sex: F
Population Size: 189
Sources:
Other AEs: Facial swelling...
Other AEs:
Facial swelling (serious, 1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
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:
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:
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:
unhealthy|pregnant
n = 189
Health Status: unhealthy|pregnant
Condition: Mild Gestational Diabetes
Sex: F
Population Size: 189
Sources:
Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer






Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
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
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
Page: 2.0
yes [IC50 15 uM]
yes [IC50 18.8 uM]
yes [IC50 199 uM]
yes [Ki 0.75 uM]
Drug as victim
PubMed

PubMed

TitleDatePubMed
The structure and function of the ATP-sensitive K+ channel in insulin-secreting pancreatic beta-cells.
1999 Apr
The Gly972-->Arg amino acid polymorphism in IRS-1 impairs insulin secretion in pancreatic beta cells.
1999 Aug
Involvement of ATP-sensitive potassium channels in a model of a delayed vascular hyporeactivity induced by lipopolysaccharide in rats.
1999 Jul
Glyburide-ciprofloxacin interaction with resistant hypoglycemia.
2000 Aug
Diflubenzuron, a benzoyl-urea insecticide, is a potent inhibitor of TCDD-induced CYP1A1 expression in HepG2 cells.
2000 May 1
Levosimendan increases diastolic coronary flow in isolated guinea-pig heart by opening ATP-sensitive potassium channels.
2001 Apr
Changes in cell volume induced by activation of the cyclic amp-dependent chloride channel in guinea-pig cardiac myocytes.
2001 Feb
Differential inhibition of functional dilation of small arterioles by indomethacin and glibenclamide.
2001 Feb
Effects of K+ channel openers on I K(ATP) of human atrial myocytes at physiological temperatures.
2001 Feb
State-dependent modification of ATP-sensitive K+ channels by phosphatidylinositol 4,5-bisphosphate.
2001 Feb
Functional and molecular characterization of receptor subtypes mediating coronary microvascular dilation to adenosine.
2001 Feb
Mechanism of prolonged vasorelaxation to ATP in the rat isolated mesenteric arterial bed.
2001 Feb
Ethanol enhances the functional recovery of stunned myocardium independent of K(ATP) channels in dogs.
2001 Feb
K(ATP)(+) channels, nitric oxide, and adenosine are not required for local metabolic coronary vasodilation.
2001 Feb
Protein kinase C and G(i/o) proteins are involved in adenosine- and ischemic preconditioning-mediated renal protection.
2001 Feb
Activation of Na(+), K(+), Cl(-)-cotransport mediates intracellular Ca(2+) increase and apoptosis induced by Pinacidil in HepG2 human hepatoblastoma cells.
2001 Feb 23
[Gestational diabetes: an alternative to insulin therapy?].
2001 Feb 3
Celecoxib-induced cholestatic hepatitis.
2001 Feb 6
The role of oxygen-derived free radicals in augmented relaxations to levcromakalim in the aorta from hypertensive rats.
2001 Jan
Verapamil prevents stretch-induced shortening of atrial effective refractory period in langendorff-perfused rabbit heart.
2001 Jan
Diabetes in elderly adults.
2001 Jan
Three types of K(+) currents in murine osteocyte-like cells (MLO-Y4).
2001 Jan
Involvement of Ca2+ -activated K+ channels in ginsenosides-induced aortic relaxation in rats.
2001 Jan
Effect of oral administration of bark extracts of Pterocarpus santalinus L. on blood glucose level in experimental animals.
2001 Jan
Role of potassium channels in regulation of brain arteriolar tone: comparison of cerebrum versus brain stem.
2001 Jan
Adenosine A1 receptor activation reduces reactive oxygen species and attenuates stunning in ventricular myocytes.
2001 Jan
Protection of cardiac myocytes via delta(1)-opioid receptors, protein kinase C, and mitochondrial K(ATP) channels.
2001 Jan
Role of mitochondrial and sarcolemmal K(ATP) channels in ischemic preconditioning of the canine heart.
2001 Jan
Dual roles of mitochondrial K(ATP) channels in diazoxide-mediated protection in isolated rabbit hearts.
2001 Jan
K(ATP) channel blockers selectively interact with A(1)-adenosine receptor mediated modulation of acetylcholine release in the rat hippocampus.
2001 Jan 19
Post-prandial hyperglycemia and its implications in pregnancy and lipid abnormalities.
2001 Jan 25
Formulation, characterization, and in vitro release of glyburide from proliposomal beads.
2001 Jan-Mar
ATP-binding cassette transporter A1 (ABCA1) functions as a cholesterol efflux regulatory protein.
2001 Jun 29
Hypoglycemic and antihyperglycemic activity of Syzygium alternifolium (Wt.) Walp. seed extracts in normal and diabetic rats.
2001 Mar
The role of K+ATP channels in the control of pre- and post-ischemic left ventricular developed pressure in septic rat hearts.
2001 Mar
Mechanism of CGRP-induced relaxation in rat intramural coronary arteries.
2001 Mar
Investigation of mechanisms that mediate reactive hyperaemia in guinea-pig hearts: role of K(ATP) channels, adenosine, nitric oxide and prostaglandins.
2001 Mar
Characterization of secretory and morphologic properties of primary cultured endocrine cells from porcine pancreata.
2001 Mar
Antiangiogenic effect of KR31372 in rat sponge implant model.
2001 Mar
Gramicidin-perforated patch analysis on HCO3- secretion through a forskolin-activated anion channel in rat parotid intralobular duct cells.
2001 Mar 1
Functional roles of cardiac and vascular ATP-sensitive potassium channels clarified by Kir6.2-knockout mice.
2001 Mar 30
Patents

Sample Use Guides

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
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
MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-IP  
USAN  
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
EP   INN   MART.   WHO-DD   WHO-IP  
INN  
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
GLIBENCLAMIDE [WHO-DD]
Common Name English
GLYBURIDE [USP-RS]
Common Name English
GLIBENCLAMIDE [INN]
Common Name English
GLYNASE
Brand 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
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
NDF-RT N0000008054
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
FDA ORPHAN DRUG 502615
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
FDA ORPHAN DRUG 518816
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
LIVERTOX 463
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
WHO-VATC QA10BB01
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
NDF-RT N0000175608
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
FDA ORPHAN DRUG 539316
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
NDF-RT N0000008054
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
FDA ORPHAN DRUG 491215
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 18.5
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
EU-Orphan Drug EU/3/15/1589
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
NCI_THESAURUS C97936
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
WHO-ATC A10BB01
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
Code System Code Type Description
EVMPD
SUB07916MIG
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY
INN
2386
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
GLYBURIDE
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY Description: A white or almost white, crystalline powder; odourless or almost odourless. Solubility: Practically insoluble in water and ether R; slightly soluble in ethanol (~750 g/l) TS and methanol R. Category: Antidiabetic agent. Storage: Glibenclamide should be kept in a well-closed container. Definition: Glibenclamide contains not less than 98.5% and not more than 101.0% of C23H28ClN3O5S, calculated with reference to the dried substance.
DRUG CENTRAL
1314
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY
MERCK INDEX
M5784
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY Merck Index
USP_CATALOG
1295505
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY USP-RS
LACTMED
Glyburide
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY
PUBCHEM
3488
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY
CAS
10238-21-8
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY
FDA UNII
SX6K58TVWC
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY
ECHA (EC/EINECS)
233-570-6
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY
MESH
D005905
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY
IUPHAR
2414
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY
WIKIPEDIA
GLIBENCLAMIDE
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY
DRUG BANK
DB01016
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY
RXCUI
4815
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY RxNorm
EPA CompTox
10238-21-8
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY
NCI_THESAURUS
C29076
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY
ChEMBL
CHEMBL472
Created by admin on Fri Jun 25 21:00:37 UTC 2021 , Edited by admin on Fri Jun 25 21:00:37 UTC 2021
PRIMARY