PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
gliclazide

2D structure

Overview

Generic Names: 1-(3-Azabicyclo(3.3.0)oct-3-yl)-3-(p-tolylsulfonyl)urea; 1-(Hexahydrocyclopenta(c)pyrrol-2(1H)-yl)-3-(p-tolylsulfonyl)urea; Gliclazida [INN-Spanish]; Gliclazidum [INN-Latin]; N-(4-Methylbenzenesulfonyl)-N'-(3-azabicyclo(3.3.0)oct-3-yl)urea
Trade Names: Diamicron; Glimicron; Nordialex
PharmGKB Accession Id: PA10892

Description

An oral sulfonylurea hypoglycemic agent which stimulates insulin secretion. PubChem (source: Drug Bank)

Indication

For the treatment of Diabetes mellitus (source: Drug Bank)

ATC Therapeutic Category

  • A10BB:Sulfonamides, urea derivatives

Pharmacology, Interactions, and Contraindications

Mechanism Of Action

Gliclazide binds to the beta cell sulfonyl urea receptor (SUR1). This binding subsequently blocks the ATP sensitive potassium channels. The binding results in closure of the channels and leads to a resulting decrease in potassium efflux leads to depolarization of the beta cells. This opens voltage-dependent calcium channels in the beta cell resulting in calmodulin activation, which in turn leads to exocytosis of insulin containing secretorty granules. (source: Drug Bank)

Pharmacology

Gliclazide is a second generation sulphonylurea which acts as a hypoglycemic agent. It stimulates beta cells of the islet of Langerhans in the pancreas to release insulin. It also enhances peripheral insulin sensitivity. Overall it potentiates insulin release and improves insulin dynamics. (source: Drug Bank)

Food Interactions

Avoid alcohol.
Take without regard to meals. (source: Drug Bank)

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic (source: Drug Bank)

Absorption

Rapidly and well absorbed but may have wide inter- and intra-individual variability. (source: Drug Bank)

Toxicity

LD<sub>50</sub>=3000 mg/kg (orally in mice) (source: Drug Bank)

Isomeric SMILES Code:

CC1=CC=C(C=C1)S(=O)(=O)NC(=O)NN2C[C@H]3CCC[C@H]3C2 (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
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
No phenotype data Genotype Data Available Literature annotations available Not annotated
ABCC8
  •   
  • PD
  •   
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2C9
  • CO
  • PD
  •   
  •   
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
NT5E
  •   
  • PD
  •   
  • FA
  •   
Publications

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

Drug Targets

Gene Description
ABCC8 Uncurated Annotation (source: Drug Bank)
ALB Uncurated Annotation (source: Drug Bank)
KCNJ1 Uncurated Annotation (source: Drug Bank)
VEGFA Uncurated Annotation (source: Drug Bank)

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)
bisoprolol 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)
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)
isocarboxazid Uncurated Annotation The MAO inhibitor increases the effect of the hypoglycemic agent (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)
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)
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)
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
Diabetes Mellitus
  •   
  • PD
  •   
  • FA
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
diabetes mellitus type 2 and obesity
  •   
  • PD
  •   
  • FA
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Diabetes Mellitus, Type 2
  • CO
  • PD
  •   
  • FA
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
Hypoglycemia
  • CO
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Obesity
  •   
  • PD
  •   
  • FA
  •   
Publications

Additional Datasets

These datasets are minimally curated and are sorted alphabetically by title.

  1. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB01120
KEGG Drug ID:
D01599
PubChem Compound ID:
3475

Common Searches

Search PubMed
Search Medline Plus
Search PubChem
Search CTD

Non-Curated Publications

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

PharmGKB integrates drug information from different sources: DrugBank, Open Eye Scientific Software.
Add New Alternate Name
Add New ATC Term
Add Cross Reference
Add a metabolite
Add a text annotation
Add a drug target
hint: enter a gene
    Add a drug interaction
    hint: enter a drug
    PharmGKB® is a registered trademark of HHS and is financially supported by NIH/NIGMS. It is managed at Stanford University (GM61374).
    ©2001-2010 PharmGKB.