U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C21H27N5O4S
Molecular Weight 445.535
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of GLIPIZIDE

SMILES

CC1=NC=C(N=C1)C(=O)NCCC2=CC=C(C=C2)S(=O)(=O)NC(=O)NC3CCCCC3

InChI

InChIKey=ZJJXGWJIGJFDTL-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/glipizide.html

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. 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. Glipizide is used 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. Glipizide is marketed by Pfizer under the brand name Glucotrol in the USA, where Pfizer sells Glucotrol in doses of 5 and 10 milligrams and Glucotrol XL (an extended release form of glipizide) in doses of 2.5, 5, and 10 milligrams. Other companies also market glipizide, most commonly extended release tablets of 5 and 10 milligrams.

Originator

Curator's Comment: first described by Ambrogi in 1971

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
GLUCOTROL

Approved Use

GLUCOTROL is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Launch Date

1984
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
523 ng/mL
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
GLIPIZIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
465 ng/mL
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
GLIPIZIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1897 ng × h/mL
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
GLIPIZIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
1878 ng × h/mL
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
GLIPIZIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1.65 h
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
GLIPIZIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
3 h
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
GLIPIZIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1.5%
GLIPIZIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
375 mg single, oral
Overdose
Dose: 375 mg
Route: oral
Route: single
Dose: 375 mg
Co-administed with::
melformin, p.o(14.5 g; single)
Sources: Page: p.565
healthy, 15
n = 1
Health Status: healthy
Age Group: 15
Sex: F
Population Size: 1
Sources: Page: p.565
Disc. AE: Hypoglycaemia...
AEs leading to
discontinuation/dose reduction:
Hypoglycaemia
Sources: Page: p.565
1 g single, oral
Overdose
Dose: 1 g
Route: oral
Route: single
Dose: 1 g
Co-administed with::
insulin, i.v(1600 u; single)
Sources: Page: p.265
unhealthy, 55
n = 1
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Age Group: 55
Sex: M
Population Size: 1
Sources: Page: p.265
Disc. AE: Hypoglycaemic encephalopathy...
AEs leading to
discontinuation/dose reduction:
Hypoglycaemic encephalopathy (grade 5)
Sources: Page: p.265
20 mg 1 times / day multiple, oral
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Co-administed with::
melformin, p.o(>/=1500 mg/day; 52 wk)
Sources: Page: p.199
unhealthy, 56.6 (9.8)
n = 584
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Age Group: 56.6 (9.8)
Sex: M+F
Population Size: 584
Sources: Page: p.199
Disc. AE: Myocardial infarction, Abortion spontaneous...
AEs leading to
discontinuation/dose reduction:
Myocardial infarction (serious, 0.17%)
Abortion spontaneous (serious, 0.17%)
Sources: Page: p.199
20 mg 1 times / day multiple, oral
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Co-administed with::
melformin, p.o(1500–2500mg/day)
Sources: Page: p.2020
unhealthy, >/=18 years
n = 408
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Age Group: >/=18 years
Sex: M+F
Population Size: 408
Sources: Page: p.2020
Disc. AE: Hypoglycemia, Pyelonephritis...
AEs leading to
discontinuation/dose reduction:
Hypoglycemia (0.7%)
Pyelonephritis (0.25%)
Sources: Page: p.2020
40 mg 1 times / day multiple, oral (total daily dose)
Recommended
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources: Page: p.3
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources: Page: p.3
Disc. AE: Cardiovascular disorder NOS...
AEs leading to
discontinuation/dose reduction:
Cardiovascular disorder NOS (grade 5)
Sources: Page: p.3
AEs

AEs

AESignificanceDosePopulation
Hypoglycaemia Disc. AE
375 mg single, oral
Overdose
Dose: 375 mg
Route: oral
Route: single
Dose: 375 mg
Co-administed with::
melformin, p.o(14.5 g; single)
Sources: Page: p.565
healthy, 15
n = 1
Health Status: healthy
Age Group: 15
Sex: F
Population Size: 1
Sources: Page: p.565
Hypoglycaemic encephalopathy grade 5
Disc. AE
1 g single, oral
Overdose
Dose: 1 g
Route: oral
Route: single
Dose: 1 g
Co-administed with::
insulin, i.v(1600 u; single)
Sources: Page: p.265
unhealthy, 55
n = 1
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Age Group: 55
Sex: M
Population Size: 1
Sources: Page: p.265
Abortion spontaneous serious, 0.17%
Disc. AE
20 mg 1 times / day multiple, oral
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Co-administed with::
melformin, p.o(>/=1500 mg/day; 52 wk)
Sources: Page: p.199
unhealthy, 56.6 (9.8)
n = 584
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Age Group: 56.6 (9.8)
Sex: M+F
Population Size: 584
Sources: Page: p.199
Myocardial infarction serious, 0.17%
Disc. AE
20 mg 1 times / day multiple, oral
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Co-administed with::
melformin, p.o(>/=1500 mg/day; 52 wk)
Sources: Page: p.199
unhealthy, 56.6 (9.8)
n = 584
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Age Group: 56.6 (9.8)
Sex: M+F
Population Size: 584
Sources: Page: p.199
Pyelonephritis 0.25%
Disc. AE
20 mg 1 times / day multiple, oral
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Co-administed with::
melformin, p.o(1500–2500mg/day)
Sources: Page: p.2020
unhealthy, >/=18 years
n = 408
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Age Group: >/=18 years
Sex: M+F
Population Size: 408
Sources: Page: p.2020
Hypoglycemia 0.7%
Disc. AE
20 mg 1 times / day multiple, oral
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Co-administed with::
melformin, p.o(1500–2500mg/day)
Sources: Page: p.2020
unhealthy, >/=18 years
n = 408
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Age Group: >/=18 years
Sex: M+F
Population Size: 408
Sources: Page: p.2020
Cardiovascular disorder NOS grade 5
Disc. AE
40 mg 1 times / day multiple, oral (total daily dose)
Recommended
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources: Page: p.3
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources: Page: p.3
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
no (pharmacogenomic study)
Comment: there were detectable differences between CYP2C19 EMs and PMs in the pharmacokinetics and pharmacodynamics of glipizide, but none of these differences were statistically significant
yes
weak (co-administration study)
Comment: rifampin decreased the AUC(0-infinity) of glipizide by 22% (P <.05) and shortened its half-life from 3.0 to 1.9 hours (P =.01); pharmacogenomic studies also performed: CYP2C9 polymorphism significantly influences the pharmacokinetics and pharmacodynamics of glipizide, which needs to be considered in clinical practice
PubMed

PubMed

TitleDatePubMed
Design and in vitro and in vivo evaluation of mucoadhesive microcapsules of glipizide for oral controlled release: a technical note.
2003
Presentation and 5-year follow-up of type 2 diabetes mellitus in African-American and Caribbean-Hispanic adolescents.
2003
[Oral antidiabetic therapy and cardiovascular complications: theoretical problem or clinical evidence?].
2003 Apr 6
Differential responsiveness of rat striatal nerve endings to the mitochondrial toxin 3-nitropropionic acid: implications for Huntington's disease.
2003 Aug
K(ATP) channels and pancreatic islet blood flow in anesthetized rats: increased blood flow induced by potassium channel openers.
2003 Aug
Effect of some penetration enhancers on the permeation of glibenclamide and glipizide through mouse skin.
2003 Dec
Hypoglycemic activity of Urtica pilulifera in streptozotocin-diabetic rats.
2003 Feb
Diabetes medicine update. Old dogs, new tricks.
2003 Jan-Feb
Performance liquid chromatographic analysis of glipizide: application to in vitro and in vivo studies.
2003 Jul
Glipizide treatment with short-term alcohol abuse resulting in subfulminant hepatic failure.
2003 Jul
Insulin secretagogues, but not glucose, stimulate an increase in [Ca2+]i in the fetal human and porcine beta-cell.
2003 Jun
Small amounts of some drugs can be toxic to young children: one pill or one swallow can require aggressive treatment.
2003 Jun
Rapid increase in the use of oral antidiabetic drugs in the United States, 1990-2001.
2003 Jun
Treatment of feline diabetes mellitus using an alpha-glucosidase inhibitor and a low-carbohydrate diet.
2003 Jun
Modification of cardiovascular response of posterior hypothalamic adenosine A(2) receptor stimulation by adenylate cylase, guanylate cyclase and by K(ATP) channel blockade in anesthetized rats.
2003 Jun 19
Multicenter, randomized, double-masked, parallel-group assessment of simultaneous glipizide/metformin as second-line pharmacologic treatment for patients with type 2 diabetes mellitus that is inadequately controlled by a sulfonylurea.
2003 Mar
Barriers to self-monitoring of blood glucose among adults with diabetes in an HMO: a cross sectional study.
2003 Mar 19
[Differences between oral antidiabetics].
2003 Mar 20
Effects of sulfonylurea hypoglycemic agents and adenosine triphosphate dependent potassium channel antagonists on ventricular arrhythmias in patients with decompensated heart failure.
2003 May
Metabolic effects of chronic glipizide gastrointestinal therapeutic system on serum glucose, insulin secretion, insulin sensitivity, and hepatic insulin extraction in glucose-tolerant, first-degree relatives of African American patients with type 2 diabetes: new insights on mechanisms of action.
2003 May
Light and scanning electron microscopic evaluation of Glyde File Prep in smear layer removal.
2003 May
Improvements in glycemic control in type 2 diabetes patients switched from sulfonylurea coadministered with metformin to glyburide-metformin tablets.
2003 May-Jun
Effects of rosiglitazone maleate when added to a sulfonylurea regimen in patients with type 2 diabetes mellitus and mild to moderate renal impairment: a post hoc analysis.
2003 Nov
Targeting postprandial hyperglycemia: a comparative study of insulinotropic agents in type 2 diabetes.
2003 Nov
Efficacy of sulfonylureas with insulin in type 2 diabetes mellitus.
2003 Nov
Risk of hypoglycaemia with oral antidiabetic agents in patients with Type 2 diabetes.
2003 Oct
Managing hemorrhagic shock: fluids on the way out--drugs on the way in?
2003 Oct
Parenteral administration of glipizide sodium salt, an inhibitor of adenosine triphosphate-sensitive potassium channels, prolongs short-term survival after severe controlled hemorrhage in rats.
2003 Oct
Weight uniformity of split tablets required by a Veterans Affairs policy.
2003 Sep-Oct
The role of sulphonylureas in the management of type 2 diabetes mellitus.
2004
Repaglinide : a pharmacoeconomic review of its use in type 2 diabetes mellitus.
2004
Beneficial metabolic effects of chronic glipizide in obese African Americans with impaired glucose tolerance: implications for primary prevention of type 2 diabetes.
2004 Apr
Cross-reactivity among p-amino group compounds in sulfonamide fixed drug eruption: diagnostic value of patch testing.
2004 Aug
Kinetics-effect relations of insulin-releasing drugs in patients with type 2 diabetes: brief overview.
2004 Dec
Induction of human CYP2C9 by rifampicin, hyperforin, and phenobarbital is mediated by the pregnane X receptor.
2004 Feb
Cost-effective management of hyperglycemia in patients with type 2 diabetes using oral agents.
2004 Jul
ppt level detection of samarium(III) with a coated graphite sensor based on an antibiotic.
2004 Jul
Prolonged hypoglycaemia secondary to extended-release form glipizide.
2004 Jul
Idiosyncratic toxicity associated with potentiated sulfonamides in the dog.
2004 Jun
Basal nitric oxide production contributes to membrane potential and vasotone regulation of guinea pig in vitro spiral modiolar artery.
2004 Mar
Simultaneous determination of glipizide and rosiglitazone unbound drug concentrations in plasma by equilibrium dialysis and liquid chromatography-tandem mass spectrometry.
2004 Mar 5
Sulfonylurea treatment of type 2 diabetes mellitus: focus on glimepiride.
2004 May
Development and evaluation of osmotically controlled oral drug delivery system of glipizide.
2004 May
Effects of glipizide GITS and glibenclamide on metabolic control, hepatic glucose production, and insulin secretion in patients with type 2 diabetes.
2004 May-Jun
Metformin-associated respiratory alkalosis.
2004 May-Jun
Tempol augments angiotensin II-induced AT2 receptor-mediated relaxation in diabetic rat thoracic aorta.
2004 Nov
The association of patient trust and self-care among patients with diabetes mellitus.
2004 Nov 16
Detection of anti-diabetics in equine plasma and urine by liquid chromatography-tandem mass spectrometry.
2004 Nov 5
Emphysematous cystitis: an unusual disease of the Genito-Urinary system suspected on imaging.
2004 Oct 5
Beta-cell insulin secretory response to oral hypoglycemic agents is blunted in humans in vivo during moderate hypoglycemia.
2004 Sep
Patents

Sample Use Guides

Initial dose: 5 mg orally once a day, 30 minutes before breakfast Maintenance dose: Up to 40 mg in divided doses 30 minutes before a meal of adequate caloric content. Doses may be increased in intervals of 2.5 to 5 mg a day according to blood glucose response. Maximum single dose: 15 mg Maximum daily dose: 40 mg
Route of Administration: Oral
Glipizide (100 uM) increased PPARγ transcriptional activity in Cos7 cells
Name Type Language
GLIPIZIDE
EP   INN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
INN   USAN  
Official Name English
1-CYCLOHEXYL-3-((P-(2-(5-METHYLPYRAZINECARBOXAMIDO)ETHYL)PHENYL)SULFONYL)UREA
Common Name English
GLIPIZIDE [USP MONOGRAPH]
Common Name English
GLIPIZIDE [JAN]
Common Name English
GLIPIZIDE COMPONENT OF METAGLIP
Common Name English
GLIPIZIDE [USAN]
Common Name English
METAGLIP COMPONENT GLIPIZIDE
Common Name English
GLIPIZIDE [VANDF]
Common Name English
K-4024
Code English
K 4024
Code English
GLIPIZIDE [USP-RS]
Common Name English
GLUCOTROL
Brand Name English
CP-28720
Code English
GLIPIZIDE SLOW RELEASE
Common Name English
GLIPIZIDE [EP MONOGRAPH]
Common Name English
GLIPIZIDE [MART.]
Common Name English
Glipizide [WHO-DD]
Common Name English
glipizide [INN]
Common Name English
GLIPIZIDE [ORANGE BOOK]
Common Name English
PYRAZINECARBOXAMIDE, N-(2-(4-((((CYCLOHEXYLAMINO)CARBONYL)AMINO)SULFONYL)PHENYL)ETHYL)-5-METHYL-
Systematic Name English
GLIPIZIDE [MI]
Common Name English
NSC-759120
Code English
CP-28,720
Code English
Classification Tree Code System Code
LIVERTOX 460
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WHO-VATC QA10BB07
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NDF-RT N0000008054
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WHO-ATC A10BB07
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NDF-RT N0000008054
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NDF-RT N0000175608
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NDF-RT N0000008054
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NCI_THESAURUS C97936
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Code System Code Type Description
CAS
29094-61-9
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PRIMARY
RS_ITEM_NUM
1292507
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PRIMARY
PUBCHEM
3478
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PRIMARY
CHEBI
5384
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PRIMARY
FDA UNII
X7WDT95N5C
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PRIMARY
NCI_THESAURUS
C29074
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PRIMARY
DAILYMED
X7WDT95N5C
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PRIMARY
ChEMBL
CHEMBL1073
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PRIMARY
DRUG BANK
DB01067
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PRIMARY
DRUG CENTRAL
1301
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PRIMARY
NSC
759120
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PRIMARY
MERCK INDEX
m5747
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PRIMARY Merck Index
INN
3090
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PRIMARY
MESH
D005913
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PRIMARY
IUPHAR
6821
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PRIMARY
WIKIPEDIA
Glipizide
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PRIMARY
RXCUI
4821
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PRIMARY RxNorm
ECHA (EC/EINECS)
249-427-6
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PRIMARY
EVMPD
SUB07927MIG
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PRIMARY
SMS_ID
100000090337
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PRIMARY
LACTMED
Glipizide
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PRIMARY
EPA CompTox
DTXSID0040676
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PRIMARY