PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
glibenclamide

2D structure

Overview

Generic Names: Apo-Glibenclamide; Glibenclamida [INN-Spanish]; Glibenclamidum [INN-Latin]; Glyburide
Trade Names: Abbenclamide; Adiab; Azuglucon; Bastiverit; Benclamin; Betanase; Betanese 5; Calabren; Cytagon; Daonil; Debtan; Dia-basan; Diabeta; Diabiphage; Dibelet; Duraglucon; Euclamin; Euglucan; Euglucon; Euglucon 5; Euglykon; GBN 5; Gen-Glybe; Gewaglucon; Gilemal; Glamide; Glibadone; Gliban; Gliben; Gliben-Puren N; Glibenbeta; Glibenclamid AL; Glibenclamid Basics; Glibenclamid Fabra; Glibenclamid Genericon; Glibenclamid Heumann; Glibenclamid Riker M.; Glibenclamid-Cophar; Glibenclamid-Ratiopharm; Glibenil; Glibens; Glibesyn; Glibet; Glibetic; Glibil; Gliboral; Glicem; Glidiabet; Glimel; Glimide; Glimidstata; Glisulin; Glitisol; Glubate; Gluben; Gluco-Tablimen; Glucobene; Glucohexal; Glucolon; Glucomid; Glucoremed; Glucoven; Glyben; Glybenclamide; Glybenzcyclamide; Glycolande; Glycomin; Glynase; Hexaglucon; Humedia; Lederglib; Libanil; Lisaglucon; Malix; Maninil; Med-Glionil; Melix; Micronase; Miglucan; Nadib; Neogluconin; Norglicem 5; Normoglucon; Novo-Glyburide; Orabetic; Pira; Praeciglucon; PresTab; Prodiabet; Renabetic; Semi-Daonil; Sugril; Suraben; Tiabet; Yuglucon
Brand Mixtures: Glucovance (Metformin + Glibenclamide)
PharmGKB Accession Id: PA449782

Description

An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide. PubChem (source: Drug Bank)

Indication

Indicated as an adjunct to diet to lower the blood glucose in patients with non-insulin-dependent diabetes mellitus (Type II) whose hyperglycemia cannot be satisfactorily controlled by diet alone. (source: Drug Bank)

ATC Therapeutic Category

  • A10BB:Sulfonamides, urea derivatives

Pharmacology, Interactions, and Contraindications

Mechanism Of Action

Sulfonylureas such as glibenclamide likely bind to ATP-sensitive potassium-channel receptors 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. (source: Drug Bank)

Pharmacology

Glibenclamide (INN), also known as glyburide (USAN), a second-generation sulfonylurea antidiabetic agent, appears to lower the 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, glibenclamide produces a mild diuresis by enhancement of renal free water clearance. Glibenclamide is twice as potent as the related second-generation agent glipizide. (source: Drug Bank)

Food Interactions

Avoid alcohol.
Avoid sugar and sugary food.
Take 30-60 minutes before breakfast. (source: Drug Bank)

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

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 contribute no significant hypoglycemic action in humans as they are only weakly active. (source: Drug Bank)

Protein Binding

Extensively bound to serum proteins (source: Drug Bank)

Absorption

Significant absorption within 1 hour and peak plasma levels are reached within 4 hours. (source: Drug Bank)

Toxicity

Oral rat LD<sub>50</sub>: > 20,000 mg/kg. Oral mouse LD<sub>50</sub>: 3250 mg/kg. (source: Drug Bank)

Isomeric SMILES Code:

COc1ccc(cc1C(=O)NCCc2ccc(cc2)S(=O)(=O)NC(=O)NC3CCCCC3)Cl (source: Drug Bank)

Curated Annotations (Curated Annotation)

  1. rs1799853 at chr10:96692037 in CYP2C9
    In a study of Scottish patients receiving sulfonylureas (n=1073), those with any CYP2C9*2 alleles were less likely to experience treatment failure, and CYP2C9*2 homozygotes had greater reductions in HbA(1c) than CYP2C9*1.
    Variant Name:
    CYP2C9*2, CYP2C9:Arg144Cys
    Related Drugs:
    glibenclamide, gliclazide, glimepiride, glipizide, sulfonamides, urea derivatives
    Related Diseases:
    Diabetes Mellitus
    Evidence:
    PMID:19794412
  2. rs1799853 at chr10:96692037 in CYP2C9
    Risk or phenotype-associated allele: CYP2C9*2, rs1799853 T allele, Cys144. Phenotype: Drug response phenotypes included (1) reaching target HbA(1c), (2) maximum HbA(1c) reduction, and (3) time to monotherapy failure. Patients homozygous for the loss-of-function CYP2C9 alleles (*2/*2, *2/*3, *3/*3) achieved greater treatment target (OR = 3.4, p = 0.0009), 0.5% greater reduction in target HbA1c concentration (p = 0.003), and lower risk of monotherapy failure based an additive genetic model (allelic hazard ratio 0.79, 95% confidence interval 0.63-0.99, p = 0.04), compared to wild-type allele (*1) carriers. Study size: 1,073 patients (578 drug-naive, 495 with prior and continued metformin exposure). Study population/ethnicity: Diabetes patients recruited in Tayside, Scotland for the Diabetes Audit and Research Tayside Study (DARTS), between 1992 and 2007, who were incident sulfonylurea users. Significance metric(s): p = (0.04 - 0.0009) Type of association: GN; PD
    Variant Name:
    CYP2C9*2, c.430C>T, mRNA 455C>T, p.Arg144Cys
    Related Drugs:
    glibenclamide, gliclazide, glimepiride, glipizide, metformin, sulfonamides, urea derivatives
    Related Diseases:
    Diabetes Mellitus, Type 2
    Evidence:
    PMID:19794412
  3. rs1057910 at chr10:96731043 in CYP2C9
    In a study of Scottish patients receiving sulfonylureas (n=1073), those with any CYP2C9*3 alleles were less likely to experience treatment failure, and CYP2C9*3 homozygotes had greater reductions in HbA(1c) than CYP2C9*1.
    Variant Name:
    CYP2C9*3, CYP2C9:Ile359Leu
    Related Drugs:
    glibenclamide, gliclazide, glimepiride, glipizide, sulfonamides, urea derivatives
    Related Diseases:
    Diabetes Mellitus
    Evidence:
    PMID:19794412
  4. rs1057910 at chr10:96731043 in CYP2C9
    Risk or phenotype-associated allele: CYP2C9*3, rs1057910 C allele, Leu359. Phenotype: Drug response phenotypes included (1) reaching target HbA(1c), (2) maximum HbA(1c) reduction, and (3) time to monotherapy failure. Patients homozygous for the loss-of-function CYP2C9 alleles (*2/*2, *2/*3, *3/*3) achieved greater treatment target (OR = 3.4, p = 0.0009), 0.5% greater reduction in target HbA1c concentration (p = 0.003), and lower risk of monotherapy failure based an additive genetic model (allelic hazard ratio 0.79, 95% confidence interval 0.63-0.99, p = 0.04), compared to wild-type allele (*1) carriers. Study size: 1,073 patients (578 drug-naive, 495 with prior and continued metformin exposure). Study population/ethnicity: Diabetes patients recruited in Tayside, Scotland for the Diabetes Audit and Research Tayside Study (DARTS), between 1992 and 2007, who were incident sulfonylurea users. Significance metric(s): p = (0.04 - 0.0009) Type of association: GN; PD
    Variant Name:
    CYP2C9*3, c.1075A>C, mRNA 11A>C, p.Ile359Leu
    Related Drugs:
    glibenclamide, gliclazide, glimepiride, glipizide, metformin, sulfonamides, urea derivatives
    Related Diseases:
    Diabetes Mellitus, Type 2
    Evidence:
    PMID:19794412
  5. rs34241435 at chr16:23220686 in SCNN1B
    A study in 207 Caucasian participants receiving farglitazar plus insulin or glyburide combination therapies this polymorphism in the SCNN1B gene was significantly associated with oedema. This variant in the promoter region of the gene was predicted to modify transcriptional interactions and in a transfected COS cell luciferase reporter gene assay exhibited higher promoter activity. The identified association has low penetrance in the fluid retention/oedema case population reflecting that SCNN1B variation may be only one of the covariates that contribute to the development of PPAR[gamma]-induced fluid retention.
    Related Drugs:
    glibenclamide, insulin-glargine
    Related Diseases:
    Diabetes Mellitus, Type 2
    Evidence:
    PMID:18004211
  6. rs889299 at chr16:23289415 in SCNN1B
    This variant in the SCNN1B gene showed the most significant association with fluid retention/oedema in participants diagnosed with T2DM receiving farglitazar plus insulin or glyburide combination therapies. But this association has low penetrance in the fluid retention/oedema case population reflecting that SCNN1B variation may be only one of the covariates that contribute to the development of PPAR[gamma]-induced fluid retention.
    Related Drugs:
    glibenclamide, insulin-glargine
    Related Diseases:
    Diabetes Mellitus, Type 2
    Evidence:
    PMID:18004211
Variant names are different names that have been used in the literature and other resources to refer to the same variant.

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Has annotations
ABCB1
  •   
  •   
  • PK
  • FA
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
ABCC1
  •   
  •   
  • PK
  • FA
  •   
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
ABCC8
  •   
  • PD
  •   
  •   
  •   
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
ABCC9
  •   
  • PD
  •   
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
ABCG2
  •   
  •   
  • PK
  • FA
  • GN
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
CYP19A1
  •   
  •   
  • PK
  • FA
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2C19
  •   
  •   
  • PK
  • FA
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
CYP2C8
  •   
  •   
  • PK
  • FA
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2C9
  •   
  • PD
  • PK
  • FA
  • GN
Publications, Variants
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2D6
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A4
  •   
  •   
  • PK
  • FA
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
NR1I2
  •   
  •   
  •   
  • FA
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
SCNN1B
  •   
  • PD
  •   
  •   
  • GN
Publications, Variants
No phenotype data Genotype Data Available Literature annotations available Has annotations
SLCO1B1
  •   
  •   
  • PK
  • FA
  •   
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
SLCO2B1
  •   
  • PD
  • PK
  • FA
  •   
Publications

A list of non-curated publications that mention this drug along with other genes is available.

Drug Targets

Gene Description
ABCA1 Uncurated Annotation (source: Drug Bank)
ABCB11 Uncurated Annotation (source: Drug Bank)
ABCC1 Uncurated Annotation (source: Drug Bank)
ABCC3 Uncurated Annotation (source: Drug Bank)
ABCC8 Uncurated Annotation (source: Drug Bank)
ABCC9 Uncurated Annotation (source: Drug Bank)
CFTR Uncurated Annotation (source: Drug Bank)
KCNJ1 Uncurated Annotation (source: Drug Bank)
KCNJ11 Uncurated Annotation (source: Drug Bank)
KCNJ5 Uncurated Annotation (source: Drug Bank)

The following drugs are in curated knowledge about this drug.

  Drug Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
fluvastatin
  •   
  •   
  • PK
  •   
  •   
Publications

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

Drug Description
acebutolol Uncurated Annotation The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
aspirin Uncurated Annotation The salicylate increases the effect of sulfonylurea (source: Drug Bank)
atenolol Uncurated Annotation The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
betaxolol Uncurated Annotation The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
bevantolol Uncurated Annotation The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
bisoprolol Uncurated Annotation The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
bosentan Uncurated Annotation Increased risk of hepatic toxicity (source: Drug Bank)
carteolol Uncurated Annotation The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
carvedilol Uncurated Annotation The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
chloramphenicol Uncurated Annotation The agent increases the effect of sulfonylurea (source: Drug Bank)
clofibrate Uncurated Annotation The agent increases the effect of sulfonylurea (source: Drug Bank)
cyclosporine Uncurated Annotation The sulfonylurea increases the effect of cyclosporine (source: Drug Bank)
diazoxide Uncurated Annotation Diazoxide/sulfonylurea: antagonism of action (source: Drug Bank)
dicumarol Uncurated Annotation The agent increases the effect of sulfonylurea (source: Drug Bank)
esmolol Uncurated Annotation The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
glucosamine Uncurated Annotation Possible hyperglycemia (source: Drug Bank)
isocarboxazid Uncurated Annotation The MAO inhibitor increases the effect of the hypoglycemic agent (source: Drug Bank)
labetalol Uncurated Annotation The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
metoprolol Uncurated Annotation The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
nadolol Uncurated Annotation The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
oxprenolol Uncurated Annotation The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
penbutolol Uncurated Annotation The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
phenelzine Uncurated Annotation The MAO inhibitor increases the effect of the hypoglycemic agent (source: Drug Bank)
phenylbutazone Uncurated Annotation Phenylbutazone increases the effect of the hypoglycemic agent (source: Drug Bank)
pindolol Uncurated Annotation The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
practolol Uncurated Annotation The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
propranolol Uncurated Annotation The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
repaglinide Uncurated Annotation Similar mode of action - questionable association (source: Drug Bank)
rifampin Uncurated Annotation Rifampin decreases the effect of sulfonylurea (source: Drug Bank)
salicylate-magnesium Uncurated Annotation The salicylate increases the effect of sulfonylurea (source: Drug Bank)
salicylate-sodium Uncurated Annotation The salicylate increases the effect of sulfonylurea (source: Drug Bank)
salsalate Uncurated Annotation The salicylate increases the effect of sulfonylurea (source: Drug Bank)
sotalol Uncurated Annotation The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
timolol Uncurated Annotation The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
tranylcypromine Uncurated Annotation The MAO inhibitor increases the effect of the hypoglycemic agent (source: Drug Bank)

Curated Information

The following diseases are in curated knowledge about this drug.

  Disease Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
Cardiomyopathy, Dilated
  •   
  • PD
  • PK
  • FA
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Diabetes Mellitus
  •   
  • PD
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Diabetes Mellitus, Type 2
  •   
  • PD
  • PK
  • FA
  • GN
Publications, Variants

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB01016
ChEBI ID:
5441
KEGG Compound ID:
C07022
KEGG Drug ID:
D00336
PubChem Compound ID:
3488
PubChem Substance ID:
167865
IUPHAR Ligand ID:
2414

Common Searches

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Non-Curated Publications

A list of non-curated publications that mention this drug is available.

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