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Identification
Name Glipizide
Accession Number DB01067 (APRD00436)
Type small molecule
Groups approved
Description

An oral hypoglycemic agent which is rapidly absorbed and completely metabolized. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Glipizida [INN-Spanish]
Glipizidum [INN-Latin]
Glydiazinamide
Salts Not Available
Brand names
Name Company
Aldiab
Digrin
Dipazide
Glibenese
Glibetin
Glican
Glide
Glidiab
Glipid
Glipizide Extended-Release Tablets
Gluco-Rite
Glucolip
Glucotrol
Glucotrol XL
Glucozide
Glupitel
Glupizide
Glyde
Melizide
Metaglip
Mindiab
Minidab
Minidiab
Minodiab
Napizide
Ozidia
Sucrazide
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Brand mixtures Not Available
Categories
  • Hypoglycemic Agents
CAS number 29094-61-9
Weight Average: 445.535
Monoisotopic: 445.178375067
Chemical Formula C21H27N5O4S
InChI Key InChIKey=ZJJXGWJIGJFDTL-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)
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Sulfonylureas
Substructures
  • Sulfonylureas
  • Amino Ketones
  • Sulfonyls
  • Benzene and Derivatives
  • Ureas and Derivatives
  • Carboxylic Acids and Derivatives
  • Benzenesulfonamides
  • Pyrazines
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Sulfonamides
  • Imines
Pharmacology
Indication For 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.
Pharmacodynamics Glipizide, 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 action Sulfonylureas 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.
Absorption Gastrointestinal absorption is uniform, rapid, and essentially complete.
Volume of distribution
  • 11 L
Protein binding 98-99%, 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.
Route of elimination The primary metabolites are inactive hydroxylation products and polar conjugates and are excreted mainly in the urine.
Half life 2-5 hours
Clearance Not Available
Toxicity The 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
Pathways Not Available
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
Form Route Strength
Tablet Oral
Tablet, extended release Oral
Prices
Unit description Cost Unit
Glipizide powder 36.11 USD g
Glucotrol XL 10 mg 24 Hour tablet 1.53 USD tablet
Glucotrol xl 10 mg tablet 1.37 USD tablet
Metaglip 5-500 mg tablet 1.33 USD tablet
Metaglip 2.5-500 mg tablet 1.32 USD tablet
Metaglip 2.5-250 mg tablet 1.2 USD tablet
Glucotrol 10 mg tablet 1.19 USD tablet
Glucotrol XL 2.5 mg 24 Hour tablet 0.99 USD tablet
Glucotrol XL 5 mg 24 Hour tablet 0.99 USD tablet
GlipiZIDE XL 10 mg 24 Hour tablet 0.84 USD tablet
Glucotrol 5 mg tablet 0.69 USD tablet
Glucotrol xl 2.5 mg tablet 0.69 USD tablet
Glucotrol xl 5 mg tablet 0.69 USD tablet
Glipizide 10 mg tablet 0.67 USD tablet
GlipiZIDE XL 2.5 mg 24 Hour tablet 0.63 USD tablet
GlipiZIDE XL 5 mg 24 Hour tablet 0.5 USD tablet
Glipizide 5 mg tablet 0.36 USD tablet
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Patents
Country Patent Number Approved Expires (estimated)
United States 5591454 1994-01-07 2014-01-07
United States 5024843 1992-09-05 2009-09-05
Canada 2024502 1997-11-11 2010-08-31
Properties
State solid
Experimental Properties
Property Value Source
melting point 208-209 °C Not Available
water solubility 37.2 mg/L Not Available
logP 1.91 HANSCH,C ET AL. (1995)
pKa 5.9 PANTEN,U ET AL. (1989)
Predicted Properties
Property Value Source
water solubility 1.64e-02 g/l ALOGPS
logP 1.83 ALOGPS
logP 1.43 ChemAxon
logS -4.4 ALOGPS
pKa (strongest acidic) 4.32 ChemAxon
pKa (strongest basic) 0.059 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 6 ChemAxon
hydrogen donor count 3 ChemAxon
polar surface area 130.15 ChemAxon
rotatable bond count 6 ChemAxon
refractivity 115.62 ChemAxon
polarizability 47.64 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00335 Link_out
PubChem Compound 3478 Link_out
PubChem Substance 46505865 Link_out
ChemSpider 3359 Link_out
BindingDB 50012956 Link_out
Therapeutic Targets Database DAP000920 Link_out
PharmGKB PA449762 Link_out
RxList http://www.rxlist.com/cgi/generic/glip.htm Link_out
Drugs.com http://www.drugs.com/glipizide.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/cx1655.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Glipizide Link_out
ATC Codes
  • A10BB07
AHFS Codes Not Available
PDB Entries Not Available
FDA label show (48.8 KB)
MSDS show (73.6 KB)
Interactions
Drug Interactions
Drug Interaction
Acebutolol Acebutolol may decrease symptoms of hypoglycemia and increase the time required for the body to compensate for hypoglycemia.
Acetylsalicylic acid Acetylsalicylic acid increases the effect of the sulfonylurea, glipizide.
Atenolol The beta-blocker, atenolol, may decrease symptoms of hypoglycemia.
Bisoprolol The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.
Carvedilol The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
Chloramphenicol Chloramphenicol may increase the effect of sulfonylurea, glipizide.
Clofibrate Clofibrate may increase the effect of sulfonylurea, glipizide.
Cyclosporine The sulfonylurea, glipizide, may increase the effect of cyclosporine.
Esmolol The beta-blocker, esmolol, may decrease symptoms of hypoglycemia.
Labetalol The beta-blocker, labetalol, may decrease symptoms of hypoglycemia.
Metoprolol The beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.
Nadolol The beta-blocker, nadolol, may decrease symptoms of hypoglycemia.
Oxprenolol The beta-blocker, oxprenolol, may decrease symptoms of hypoglycemia.
Phenylbutazone Phenylbutazone increases the effect of the hypoglycemic agent
Pindolol The beta-blocker, pindolol, may decrease symptoms of hypoglycemia.
Propranolol The beta-blocker, propranolol, may decrease symptoms of hypoglycemia.
Rifampin Rifampin may decrease the effect of sulfonylurea, glipizide.
Somatropin recombinant Somatropin may antagonize the hypoglycemic effect of glipizide. Monitor for changes in fasting and postprandial blood sugars.
Timolol The beta-blocker, timolol, may decrease symptoms of hypoglycemia.
Tolbutamide Tolbutamide, 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 transporter sub-family C member 8

Pharmacological action: yes
Actions: inhibitor

Putative subunit of the beta-cell ATP-sensitive potassium channel (KATP). Regulator of ATP-sensitive K+ channels and insulin release

Organism class: human
UniProt ID: Q09428 Link_out
Gene: ABCC8 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: agonist

Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the receptor binds to a promoter element in the gene for acyl-CoA oxidase and activates its transcription. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis

Organism class: human
UniProt ID: P37231 Link_out
Gene: PPARG Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19