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Identification
NameGlipizide
Accession NumberDB01067  (APRD00436)
Typesmall molecule
Groupsapproved
Description

An oral hypoglycemic agent which is rapidly absorbed and completely metabolized. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
GlipizidaSpanishINN
GlipizidumLatinINN
SaltsNot Available
Brand names
NameCompany
GlibenesePfizer
GlibénèseDexo
GlibetinJohnson
GlipinSwiss Pharm
GlipizideERNot Available
GlixYSP
GlucotrolPfizer
Glucotrol XLPfizer
MindiabPfizer
MinidiabPfizer
Zitrol XRSquare
Brand mixturesNot Available
Categories
CAS number29094-61-9
WeightAverage: 445.535
Monoisotopic: 445.178375067
Chemical FormulaC21H27N5O4S
InChI KeyZJJXGWJIGJFDTL-UHFFFAOYSA-N
InChI
InChI=1S/C21H27N5O4S/c1-15-13-24-19(14-23-15)20(27)22-12-11-16-7-9-18(10-8-16)31(29,30)26-21(28)25-17-5-3-2-4-6-17/h7-10,13-14,17H,2-6,11-12H2,1H3,(H,22,27)(H2,25,26,28)
IUPAC Name
N-[2-(4-{[(cyclohexylcarbamoyl)amino]sulfonyl}phenyl)ethyl]-5-methylpyrazine-2-carboxamide
SMILES
CC1=CN=C(C=N1)C(=O)NCCC1=CC=C(C=C1)S(=O)(=O)NC(=O)NC1CCCCC1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassBenzenesulfonamides
Direct parentBenzenesulfonamides
Alternative parentsPyrazinecarboxamides; Phenethylamines; Sulfonylureas; Sulfonyls; Sulfonamides; Secondary Carboxylic Acid Amides; Polyamines; Enolates; Carboxylic Acids
Substituentssulfonylurea; pyrazine; sulfonyl; sulfonic acid derivative; sulfonamide; secondary carboxylic acid amide; carboxamide group; carboxylic acid derivative; polyamine; enolate; 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 use as an adjunct to diet for the control of hyperglycemia and its associated symptomatology in patients with non-insulin-dependent diabetes mellitus (NIDDM; type II), formerly known as maturity-onset diabetes, after an adequate trial of dietary therapy has proved unsatisfactory.
PharmacodynamicsGlipizide, a second-generation sulfonylurea, is used with diet to lower blood glucose in patients with diabetes mellitus type II. The primary mode of action of glipizide in experimental animals appears to be the stimulation of insulin secretion from the beta cells of pancreatic islet tissue and is thus dependent on functioning beta cells in the pancreatic islets. In humans glipizide 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. In man, stimulation of insulin secretion by glipizide in response to a meal is undoubtedly of major importance. Fasting insulin levels are not elevated even on long-term glipizide administration, but the postprandial insulin response continues to be enhanced after at least 6 months of treatment. Some patients fail to respond initially, or gradually lose their responsiveness to sulfonylurea drugs, including glipizide.
Mechanism of actionSulfonylureas 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.
AbsorptionGastrointestinal absorption is uniform, rapid, and essentially complete.
Volume of distribution
  • 11 L
Protein binding98-99%, primarily to albumin.
Metabolism

Hepatic. The major metabolites of glipizide are products of aromatic hydroxylation and have no hypoglycemic activity. A minor metabolite which accounts for less than 2% of a dose, an acetylaminoethyl benzine derivatives, is reported to have 1/10 to 1/3 as much hypoglycemic activity as the parent compound.

SubstrateEnzymesProduct
Glipizide
Not Available
3-cis-HydroxyglipizideDetails
Glipizide
4-trans-HydroxyglipizideDetails
Route of eliminationThe primary metabolites are inactive hydroxylation products and polar conjugates and are excreted mainly in the urine.
Half life2-5 hours
ClearanceNot Available
ToxicityThe acute oral toxicity was extremely low in all species tested (LD50 greater than 4 g/kg). Overdosage of sulfonylureas including glipizide can produce hypoglycemia.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated Effects
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeEffectReference(s)
Cytochrome P450 2C9
Gene symbol: CYP2C9
UniProt: P11712
rs1057910 CYP2C9*1C AllelePoor drug metabolizer, lower dose requirements10208645
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9262
Blood Brain Barrier + 0.5599
Caco-2 permeable - 0.7025
P-glycoprotein substrate Substrate 0.5326
P-glycoprotein inhibitor I Non-inhibitor 0.7469
P-glycoprotein inhibitor II Non-inhibitor 0.9302
Renal organic cation transporter Non-inhibitor 0.8322
CYP450 2C9 substrate Substrate 0.5731
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Non-substrate 0.719
CYP450 1A2 substrate Non-inhibitor 0.9501
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 0.8682
Ames test Non AMES toxic 0.7745
Carcinogenicity Non-carcinogens 0.826
Biodegradation Not ready biodegradable 0.9703
Rat acute toxicity 2.1662 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9118
hERG inhibition (predictor II) Non-inhibitor 0.8539
Pharmacoeconomics
Manufacturers
  • Watson laboratories inc
  • Pfizer inc
  • Alphapharm party ltd
  • Apotex inc
  • Caraco pharmaceutical laboratories ltd
  • Endo pharmaceuticals inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mylan pharmaceuticals inc
  • Par pharmaceutical inc
  • Pliva inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
Packagers
Dosage forms
FormRouteStrength
TabletOral
Tablet, extended releaseOral
Prices
Unit descriptionCostUnit
Glipizide powder36.11USDg
Glucotrol XL 10 mg 24 Hour tablet1.53USDtablet
Glucotrol xl 10 mg tablet1.37USDtablet
Metaglip 5-500 mg tablet1.33USDtablet
Metaglip 2.5-500 mg tablet1.32USDtablet
Metaglip 2.5-250 mg tablet1.2USDtablet
Glucotrol 10 mg tablet1.19USDtablet
Glucotrol XL 2.5 mg 24 Hour tablet0.99USDtablet
Glucotrol XL 5 mg 24 Hour tablet0.99USDtablet
GlipiZIDE XL 10 mg 24 Hour tablet0.84USDtablet
Glucotrol 5 mg tablet0.69USDtablet
Glucotrol xl 2.5 mg tablet0.69USDtablet
Glucotrol xl 5 mg tablet0.69USDtablet
Glipizide 10 mg tablet0.67USDtablet
GlipiZIDE XL 2.5 mg 24 Hour tablet0.63USDtablet
GlipiZIDE XL 5 mg 24 Hour tablet0.5USDtablet
Glipizide 5 mg tablet0.36USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States55914541994-01-072014-01-07
United States50248431992-09-052009-09-05
Canada20245021997-11-112010-08-31
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point200-203U.S. Patent 3,669,966.
water solubility37.2 mg/LNot Available
logP1.91HANSCH,C ET AL. (1995)
pKa5.9PANTEN,U ET AL. (1989)
Predicted Properties
PropertyValueSource
water solubility1.64e-02 g/lALOGPS
logP1.83ALOGPS
logP1.43ChemAxon
logS-4.4ALOGPS
pKa (strongest acidic)4.32ChemAxon
pKa (strongest basic)0.059ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count6ChemAxon
hydrogen donor count3ChemAxon
polar surface area130.15ChemAxon
rotatable bond count6ChemAxon
refractivity115.62ChemAxon
polarizability47.64ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Suresh Kumar Gidwani, Purushottam Singnurkar, Prashant Kumar Tewari, “Sustained release pharmaceutical composition containing glipizide and method for producing same.” U.S. Patent US6270797, issued February, 2000.

US6270797
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00335
PubChem Compound3478
PubChem Substance46505865
ChemSpider3359
BindingDB50012956
Therapeutic Targets DatabaseDAP000920
PharmGKBPA449762
RxListhttp://www.rxlist.com/cgi/generic/glip.htm
Drugs.comhttp://www.drugs.com/glipizide.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/cx1655.shtml
WikipediaGlipizide
ATC CodesA10BB07
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelshow(48.8 KB)
MSDSshow(73.6 KB)
Interactions
Drug Interactions
Drug
AcebutololAcebutolol may decrease symptoms of hypoglycemia and increase the time required for the body to compensate for hypoglycemia.
Acetylsalicylic acidAcetylsalicylic acid increases the effect of the sulfonylurea, glipizide.
AtenololThe beta-blocker, atenolol, may decrease symptoms of hypoglycemia.
BisoprololThe beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.
CarvedilolThe beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
ChloramphenicolChloramphenicol may increase the effect of sulfonylurea, glipizide.
ClofibrateClofibrate may increase the effect of sulfonylurea, glipizide.
CyclosporineThe sulfonylurea, glipizide, may increase the effect of cyclosporine.
EsmololThe beta-blocker, esmolol, may decrease symptoms of hypoglycemia.
LabetalolThe beta-blocker, labetalol, may decrease symptoms of hypoglycemia.
MetoprololThe beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.
NadololThe beta-blocker, nadolol, may decrease symptoms of hypoglycemia.
OxprenololThe beta-blocker, oxprenolol, may decrease symptoms of hypoglycemia.
PhenylbutazonePhenylbutazone increases the effect of the hypoglycemic agent
PindololThe beta-blocker, pindolol, may decrease symptoms of hypoglycemia.
PropranololThe beta-blocker, propranolol, may decrease symptoms of hypoglycemia.
RifampicinRifampin may decrease the effect of sulfonylurea, glipizide.
Somatropin recombinantSomatropin may antagonize the hypoglycemic effect of glipizide. Monitor for changes in fasting and postprandial blood sugars.
TimololThe beta-blocker, timolol, may decrease symptoms of hypoglycemia.
TolbutamideTolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Glipizide. Consider alternate therapy or monitor for changes in Glipizide therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
Food Interactions
  • Avoid alcohol.
  • Avoid sugar and sugary food.
  • Take 30-60 minutes before breakfast.

Targets

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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

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

References:

  1. Gribble FM, Ashcroft FM: Sulfonylurea sensitivity of adenosine triphosphate-sensitive potassium channels from beta cells and extrapancreatic tissues. Metabolism. 2000 Oct;49(10 Suppl 2):3-6. Pubmed
  2. Harrower A: Gliclazide modified release: from once-daily administration to 24-hour blood glucose control. Metabolism. 2000 Oct;49(10 Suppl 2):7-11. Pubmed
  3. Lawrence CL, Proks P, Rodrigo GC, Jones P, Hayabuchi Y, Standen NB, Ashcroft FM: Gliclazide produces high-affinity block of KATP channels in mouse isolated pancreatic beta cells but not rat heart or arterial smooth muscle cells. Diabetologia. 2001 Aug;44(8):1019-25. Pubmed
  4. Reimann F, Ashcroft FM, Gribble FM: Structural basis for the interference between nicorandil and sulfonylurea action. Diabetes. 2001 Oct;50(10):2253-9. Pubmed
  5. Proks P, Reimann F, Green N, Gribble F, Ashcroft F: Sulfonylurea stimulation of insulin secretion. Diabetes. 2002 Dec;51 Suppl 3:S368-76. Pubmed

2. Peroxisome proliferator-activated receptor gamma

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Peroxisome proliferator-activated receptor gamma P37231 Details

References:

  1. Scarsi M, Podvinec M, Roth A, Hug H, Kersten S, Albrecht H, Schwede T, Meyer UA, Rucker C: Sulfonylureas and glinides exhibit peroxisome proliferator-activated receptor gamma activity: a combined virtual screening and biological assay approach. Mol Pharmacol. 2007 Feb;71(2):398-406. Epub 2006 Nov 2. 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

2. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. 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 January 11, 2014 08:47