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Identification
NameGlimepiride
Accession NumberDB00222  (APRD00381)
Typesmall molecule
Groupsapproved
Description

Glimepiride is the first III generation sulphonyl urea it is a very potent sulphonyl urea with long duration of action.

Structure
Thumb
Synonyms
SynonymLanguageCode
AmarylNot AvailableNot Available
GlimepiridaSpanishINN
GlimépirideFrenchINN
GlimepiridumLatinINN
SaltsNot Available
Brand names
NameCompany
AmarylSanofi-Aventis
GLIMPIDRanbaxy Laboratories
GLIMYDr.Reddy's Labs
Brand mixtures
Brand NameIngredients
Avandarylglimepiride + rosiglitazone maleate
DuetactGlimepiride + Pioglitazone
Categories
CAS number93479-97-1
WeightAverage: 490.616
Monoisotopic: 490.224990908
Chemical FormulaC24H34N4O5S
InChI KeyWIGIZIANZCJQQY-UHFFFAOYSA-N
InChI
InChI=1S/C24H34N4O5S/c1-4-21-17(3)15-28(22(21)29)24(31)25-14-13-18-7-11-20(12-8-18)34(32,33)27-23(30)26-19-9-5-16(2)6-10-19/h7-8,11-12,16,19H,4-6,9-10,13-15H2,1-3H3,(H,25,31)(H2,26,27,30)
IUPAC Name
3-ethyl-4-methyl-N-{2-[4-({[(4-methylcyclohexyl)carbamoyl]amino}sulfonyl)phenyl]ethyl}-2-oxo-2,5-dihydro-1H-pyrrole-1-carboxamide
SMILES
CCC1=C(C)CN(C(=O)NCCC2=CC=C(C=C2)S(=O)(=O)NC(=O)NC2CCC(C)CC2)C1=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassBenzenesulfonamides
Direct parentBenzenesulfonamides
Alternative parentsPhenethylamines; Pyrroline Carboxylic Acids and Derivatives; Ureides; Sulfonylureas; N-substituted Carboxylic Acid Imides; Sulfonamides; Sulfonyls; Tertiary Carboxylic Acid Amides; Tertiary Amines; Polyamines; Carboxylic Acids
Substituentspyrroline carboxylic acid or derivative; sulfonylurea; ureide; carboxylic acid imide, n-substituted; tertiary carboxylic acid amide; sulfonamide; sulfonic acid derivative; sulfonyl; pyrroline; carboxamide group; tertiary amine; carboxylic acid derivative; polyamine; carboxylic acid; amine; 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
IndicationFor concomitant use with insulin for the treatment of noninsulin-dependent (type 2) diabetes mellitus.
PharmacodynamicsGlimepiride, like glyburide and glipizide, is a "second-generation" sulfonylurea agents. Glimepiride is used with diet to lower blood glucose by increasing the secretion of insulin from pancreas and increasing the sensitivity of peripheral tissues to insulin.
Mechanism of actionThe mechanism of action of glimepiride in lowering blood glucose appears to be dependent on stimulating the release of insulin from functioning pancreatic beta cells, and increasing sensitivity of peripheral tissues to insulin. Glimepiride likely binds to ATP-sensitive potassium channel receptors on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Membrane depolarization stimulates calcium ion influx through voltage-sensitive calcium channels. This increase in intracellular calcium ion concentration induces the secretion of insulin.
AbsorptionCompletely (100%) absorbed following oral administration.
Volume of distribution
  • 21.8 ± 13.9 L [Volunteers]
  • 19.8 ± 12.7 L [Patients with Type 2 diabetes, Single Dose]
  • 37.1 ± 18.2 L [Patients with Type 2 diabetes, Multiple Dose]
Protein bindingOver 99.5% bound to plasma protein.
Metabolism

Hepatic. Following either an intravenous or oral dose, glimepiride is completely metabolized by oxidative biotransformation to a major metabolite, cyclohexyl hydroxymethyl derivative (M1), via the hepatic cytochrome P450 II C9 subsystem. M1 is further metabolized to the carboxyl derivative (M2) by one or several cytosolic enzymes. M1, but not M2, possessed approximately one third of the pharmacologic activity of its parent in an animal model. However, whether the glucose-lowering effect of M1 is clinically significant is not clear.

SubstrateEnzymesProduct
Glimepiride
Cyclohexyl hydroxymethyl glimepirideDetails
Cyclohexyl hydroxymethyl glimepiride
Cyclohexyl carboxyl glimepirideDetails
Route of eliminationNot Available
Half lifeApproximately 5 hours following single dose.
Clearance
  • 52.1 +/- 16.0 mL/min [Normal subjects with single oral dose]
  • 48.5 +/- 29.3 mL/min [Patients with Type 2 diabetes, with single oral dose]
  • 52.7 +/- 40.3 mL/min [Patients with Type 2 diabetes, with multiple oral dose]
  • 47.8 mL/min [healthy after intravenous (IV) dosing]
ToxicitySevere hypoglycemic reactions with coma, seizure, or other neurological impairment.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.986
Blood Brain Barrier + 0.7322
Caco-2 permeable - 0.6809
P-glycoprotein substrate Substrate 0.7501
P-glycoprotein inhibitor I Non-inhibitor 0.6556
P-glycoprotein inhibitor II Inhibitor 0.6124
Renal organic cation transporter Non-inhibitor 0.8241
CYP450 2C9 substrate Substrate 0.5661
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Non-substrate 0.5978
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Inhibitor 0.8949
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.8309
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8599
Ames test Non AMES toxic 0.6392
Carcinogenicity Non-carcinogens 0.7301
Biodegradation Not ready biodegradable 0.68
Rat acute toxicity 2.4158 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.7714
hERG inhibition (predictor II) Non-inhibitor 0.8263
Pharmacoeconomics
Manufacturers
  • Sanofi aventis us llc
  • Accord healthcare inc
  • Carlsbad technology inc
  • Corepharma llc
  • Dr reddys laboratories ltd
  • Genpharm inc
  • Invagen pharmaceuticals inc
  • Mylan pharmaceuticals inc
  • Ranbaxy laboratories ltd
  • Teva pharmaceuticals usa inc
  • Vintage pharmaceuticals llc
  • Watson laboratories inc
  • Watson laboratories inc florida
Packagers
Dosage forms
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
Amaryl 4 mg tablet2.11USDtablet
Amaryl 2 mg tablet1.25USDtablet
Glimepiride 4 mg tablet1.25USDtablet
Amaryl 1 mg tablet0.88USDtablet
Glimepiride 2 mg tablet0.67USDtablet
Glimepiride 1 mg tablet0.42USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point207 °CNot Available
water solubilityInsolubleNot Available
logP3.5Not Available
Predicted Properties
PropertyValueSource
water solubility3.84e-02 g/lALOGPS
logP2.82ALOGPS
logP3.12ChemAxon
logS-4.1ALOGPS
pKa (strongest acidic)4.32ChemAxon
pKa (strongest basic)-3.7ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count5ChemAxon
hydrogen donor count3ChemAxon
polar surface area124.68ChemAxon
rotatable bond count6ChemAxon
refractivity129.8ChemAxon
polarizability53.86ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Suresh Kadam, Venkatasubramanian Tarur, Sanjay Naik, Sachin Gavhane, “Process for preparation of substantially pure glimepiride.” U.S. Patent US20070082943, issued April 12, 2007.

US20070082943
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00593
KEGG CompoundC07669
PubChem Compound3476
PubChem Substance46508842
ChemSpider3357
ChEBI5383
ChEMBLCHEMBL1481
Therapeutic Targets DatabaseDAP000132
PharmGKBPA449761
Drug Product Database2245274
RxListhttp://www.rxlist.com/cgi/generic/glimepiride.htm
Drugs.comhttp://www.drugs.com/cdi/glimepiride.html
WikipediaGlimepiride
ATC CodesA10BB12
AHFS Codes
  • 68:20.20
PDB EntriesNot Available
FDA labelshow(176 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
CyclosporineThe sulfonylurea, glimepiride, may increase the effect of cyclosporine.
GemfibrozilGemfibrozil increases the effect and toxicity of rosiglitazone/pioglitazone
GlucosaminePossible hyperglycemia
KetoconazoleKetoconazole increases the effect of rosiglitazone
RifampicinRifampin may decrease the effect of sulfonylurea, glimepiride.
Somatropin recombinantSomatropin may antagonize the hypoglycemic effect of glimepiride. Monitor for changes in fasting and postprandial blood sugars.
TolbutamideTolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Glimepiride. Consider alternate therapy or monitor for changes in Glimepiride therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
Food Interactions
  • Avoid alcohol.
  • Even though food reduces product absorption, the manufacturer recommends taking the product with the first meal of the day.

Targets

1. ATP-sensitive inward rectifier potassium channel 11

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

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

References:

  1. Song DK, Ashcroft FM: Glimepiride block of cloned beta-cell, cardiac and smooth muscle K(ATP) channels. Br J Pharmacol. 2001 May;133(1):193-9. Pubmed
  2. Lawrence CL, Rainbow RD, Davies NW, Standen NB: Effect of metabolic inhibition on glimepiride block of native and cloned cardiac sarcolemmal K(ATP) channels. Br J Pharmacol. 2002 Jul;136(5):746-52. Pubmed
  3. Bataille D: [Molecular mechanisms of insulin secretion]. Diabetes Metab. 2002 Dec;28(6 Suppl):4S7-13. Pubmed

2. ATP-sensitive inward rectifier potassium channel 1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

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

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Proks P, Reimann F, Green N, Gribble F, Ashcroft F: Sulfonylurea stimulation of insulin secretion. Diabetes. 2002 Dec;51 Suppl 3:S368-76. Pubmed
  4. Bataille D: [Molecular mechanisms of insulin secretion]. Diabetes Metab. 2002 Dec;28(6 Suppl):4S7-13. Pubmed

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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inducer

Components

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

References:

  1. Muller G, Hartz D, Punter J, Okonomopulos R, Kramer W: Differential interaction of glimepiride and glibenclamide with the beta-cell sulfonylurea receptor. I. Binding characteristics. Biochim Biophys Acta. 1994 May 11;1191(2):267-77. Pubmed
  2. Kramer W, Muller G, Geisen K: Characterization of the molecular mode of action of the sulfonylurea, glimepiride, at beta-cells. Horm Metab Res. 1996 Sep;28(9):464-8. Pubmed
  3. Kramer W, Muller G, Girbig F, Gutjahr U, Kowalewski S, Hartz D, Summ HD: The molecular interaction of sulfonylureas with beta-cell ATP-sensitive K(+)-channels. Diabetes Res Clin Pract. 1995 Aug;28 Suppl:S67-80. Pubmed

Enzymes

1. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. 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
  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

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Drug created on June 13, 2005 07:24 / Updated on September 25, 2013 14:06