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

Details

Stereochemistry ABSOLUTE
Molecular Formula C27H36N2O4
Molecular Weight 452.5857
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of REPAGLINIDE

SMILES

CCOC1=C(C=CC(CC(=O)N[C@@H](CC(C)C)C2=C(C=CC=C2)N3CCCCC3)=C1)C(O)=O

InChI

InChIKey=FAEKWTJYAYMJKF-QHCPKHFHSA-N
InChI=1S/C27H36N2O4/c1-4-33-25-17-20(12-13-22(25)27(31)32)18-26(30)28-23(16-19(2)3)21-10-6-7-11-24(21)29-14-8-5-9-15-29/h6-7,10-13,17,19,23H,4-5,8-9,14-16,18H2,1-3H3,(H,28,30)(H,31,32)/t23-/m0/s1

HIDE SMILES / InChI

Molecular Formula C27H36N2O4
Molecular Weight 452.5857
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/12196472

Repaglinide is antidiabetic drug, which is sold under several names including, Prandin in the U.S., Surepost in Japan and GlucoNorm in Canada. It is an oral blood glucose-lowering drug of the meglitinide class used in the management of type 2 diabetes mellitus (also known as non-insulin dependent diabetes mellitus or NIDDM). Repaglinide lowers blood glucose levels by stimulating the release of insulin from the pancreas. This action is dependent upon functioning beta (ß) cells in the pancreatic islets. Insulin secretion by pancreatic β cells is partly controlled by cellular membrane potential. Membrane potential is regulated through an inverse relationship between the activity of cell membrane ATP-sensitive potassium channels (ABCC8) and extracellular glucose concentrations. Extracellular glucose enters the cell via GLUT2 (SLC2A2) transporters. Once inside the cell, glucose is metabolized to produce ATP. High concentrations of ATP inhibit ATP-sensitive potassium channels causing membrane depolarization. High glucose concentrations cause ATP-sensitive potassium channels to close resulting in membrane depolarization and opening of L-type calcium channels. The influx of calcium ions stimulates calcium-dependent exocytosis of insulin granules. Repaglinide closes ATP-dependent potassium channels in the ß-cell membrane by binding at characterizable sites. This potassium channel blockade depolarizes the ß-cell, which leads to an opening of calcium channels. The resulting increased calcium influx induces insulin secretion. The ion channel mechanism is highly tissue selective with low affinity for heart and skeletal muscle. Repaglinide is completely metabolized by oxidative biotransformation and direct conjugation with glucuronic acid after either an IV or oral dose.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
21.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
PRANDIN

Approved Use

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

Launch Date

1997
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
65.8 ng/mL
4 mg 1 times / day multiple, oral
dose: 4 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
REPAGLINIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
447.4 ng × h/mL
4 mg 1 times / day multiple, oral
dose: 4 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
REPAGLINIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1.4 h
4 mg 1 times / day multiple, oral
dose: 4 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
REPAGLINIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
2%
4 mg 1 times / day multiple, oral
dose: 4 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
REPAGLINIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
4 mg 4 times / day multiple, oral
Recommended
Dose: 4 mg, 4 times / day
Route: oral
Route: multiple
Dose: 4 mg, 4 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources: Page: p.1
Disc. AE: Hypoglycemia...
AEs leading to
discontinuation/dose reduction:
Hypoglycemia
Sources: Page: p.1
AEs

AEs

AESignificanceDosePopulation
Hypoglycemia Disc. AE
4 mg 4 times / day multiple, oral
Recommended
Dose: 4 mg, 4 times / day
Route: oral
Route: multiple
Dose: 4 mg, 4 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources: Page: p.1
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
[Repaglinide, potentially a therapeutic improvement for diabetes mellitus type 2].
2001 Aug 11
Combination therapy in type 2 diabetes: the role of repaglinide.
2001 Jan 25
Current understanding regarding the role of repaglinide in post-prandial hyperglycemia.
2001 Jan 25
The cytochrome P4503A4 inhibitor clarithromycin increases the plasma concentrations and effects of repaglinide.
2001 Jul
[Repaglinide].
2001 May 11
Nateglinide therapy for type 2 diabetes mellitus.
2001 Nov
Insulinotropic meglitinide analogues.
2001 Nov 17
The effects of mitiglinide (KAD-1229), a new anti-diabetic drug, on ATP-sensitive K+ channels and insulin secretion: comparison with the sulfonylureas and nateglinide.
2001 Nov 9
Rapid acting insulinotropic agents: restoration of early insulin secretion as a physiologic approach to improve glucose control.
2001 Sep
Effect of insulinotropic agent nateglinide on Kv and Ca(2+) channels in pancreatic beta-cell.
2001 Sep 14
Patient perceptions of prandial oral therapy for type 2 diabetes.
2001 Sep-Oct
Interactions between antiretroviral drugs and drugs used for the therapy of the metabolic complications encountered during HIV infection.
2002
Response to Schmitz. Optimizing insulin secretagogue therapy in patients with type 2 diabetes: a randomized double-blind study with repaglinide.
2002 Aug
High-frequency insulin pulsatility and type 2 diabetes: from physiology and pathophysiology to clinical pharmacology.
2002 Dec
Repaglinide at a cellular level.
2002 Dec
Early changes in beta-cell function and insulin pulsatility as predictors for type 2 diabetes.
2002 Dec
Sulfonylurea stimulation of insulin secretion.
2002 Dec
Optimizing insulin secretagogue therapy in patients with type 2 diabetes: a randomized double-blind study with repaglinide.
2002 Feb
Modeling the pharmacokinetics and pharmacodynamics of a unique oral hypoglycemic agent using neural networks.
2002 Jan
Type 2 diabetes management.
2002 Jan
Oral antihyperglycemic therapy for type 2 diabetes: scientific review.
2002 Jan 16
Gateways to clinical trials.
2002 Jan-Feb
Nateglinide, but not repaglinide, stimulates growth hormone release in rat pituitary cells by inhibition of K channels and stimulation of cyclic AMP-dependent exocytosis.
2002 Jul
Hypoglycemia probably due to accidental intake of repaglinide.
2002 Nov
Repaglinide versus metformin in combination with bedtime NPH insulin in patients with type 2 diabetes established on insulin/metformin combination therapy.
2002 Oct
Repaglinide versus glibenclamide treatment of Type 2 diabetes during Ramadan fasting.
2002 Oct
[Repaglinide (NN-623)].
2002 Sep
Economic model of first-line drug strategies to achieve recommended glycaemic control in newly diagnosed type 2 diabetes mellitus.
2003
Pharmacokinetics of repaglinide in healthy caucasian and Japanese subjects.
2003 Jan
The effect of repaglinide on insulin secretion and oxidative stress in type 2 diabetic patients.
2003 Jan
A comparison of costs for four oral antidiabetic regimens within a managed care population.
2003 Jul
Efficacy and safety of combination therapy: repaglinide plus metformin versus nateglinide plus metformin.
2003 Jul
[Meglitinide analogs: new insulinotropic agents for the treatment of non-insulin dependent diabetes].
2003 Jun
Influence of drugs interacting with CYP3A4 on the pharmacokinetics, pharmacodynamics, and safety of the prandial glucose regulator repaglinide.
2003 Jun
The effect of prandial glucose regulation with repaglinide on treatment satisfaction, wellbeing and health status in patients with pharmacotherapy naïve Type 2 diabetes: a placebo-controlled, multicentre study.
2003 Jun
The mechanisms underlying the unique pharmacodynamics of nateglinide.
2003 Mar
The role of oral antidiabetic agents: why and when to use an early-phase insulin secretion agent in Type II diabetes mellitus.
2003 Mar
Metformin-induced hemolytic anemia in a patient with glucose-6- phosphate dehydrogenase deficiency.
2003 Mar
Differential selectivity of insulin secretagogues: mechanisms, clinical implications, and drug interactions.
2003 Mar-Apr
Neuronal calcium sensor proteins are direct targets of the insulinotropic agent repaglinide.
2003 Oct 1
Cardiovascular risk in type 2 diabetics and pharmacological regulation of mealtime glucose excursions.
2003 Sep
Lack of effect of acute repaglinide administration on postprandial lipaemia in patients with type 2 diabetes mellitus.
2003 Sep
CYP2C8 and CYP3A4 are the principal enzymes involved in the human in vitro biotransformation of the insulin secretagogue repaglinide.
2003 Sep
Patents

Sample Use Guides

There is no fixed dosage regimen for the management of type 2 diabetes with PRANDIN (repaglinide). PRANDIN doses are usually taken within 15 minutes of the meal but time may vary from immediately preceding the meal to as long as 30 minutes before the meal. For patients not previously treated or whose HbA1c is < 8%, the starting dose should be 0.5 mg with each meal. For patients previously treated with blood glucose-lowering drugs and whose HbA1c is > 8%, the initial dose is 1 or 2 mg with each meal preprandially.
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment: In vitro studies suggested significant active hepatic uptake of repaglinide. Mechanistic model adequately described repaglinide pharmacokinetics, and successfully predicted DDIs with several OATP1B1 and CYP3A4 inhibitors (<10% error). Furthermore, repaglinide-gemfibrozil interaction at therapeutic dose was closely predicted using in vitro fraction metabolism for CYP2C8 (0.71), when primarily considering reversible inhibition of OATP1B1 and mechanism-based inactivation of CYP2C8 by gemfibrozil and gemfibrozil 1-O-β-glucuronide.
Unknown
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:52:42 GMT 2023
Edited
by admin
on Fri Dec 15 15:52:42 GMT 2023
Record UNII
668Z8C33LU
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
REPAGLINIDE
EMA EPAR   EP   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN   INN  
Official Name English
REPAGLINIDE [EP MONOGRAPH]
Common Name English
NSC-759893
Code English
PRANDIN
Brand Name English
REPAGLINIDE [MART.]
Common Name English
REPAGLINIDE [VANDF]
Common Name English
Repaglinide [WHO-DD]
Common Name English
A10BX02
Code English
REPAGLINIDE [USAN]
Common Name English
AGEE-623ZW
Code English
REPAGLINIDE [USP-RS]
Common Name English
REPAGLINIDE [ORANGE BOOK]
Common Name English
REPAGLINIDE [JAN]
Common Name English
REPAGLINIDE [MI]
Common Name English
(+)-2-ETHOXY-.ALPHA.-(((S)-.ALPHA.-ISOBUTYL-O-PIPERIDINOBENZYL)CARBAMOYL)-P-TOLUIC ACID
Common Name English
REPAGLINIDE [USP MONOGRAPH]
Common Name English
AG-EE 623 ZW
Code English
AG-EE-623-ZW
Code English
AG-EE-623ZW
Code English
REPAGLINIDE [EMA EPAR]
Common Name English
repaglinide [INN]
Common Name English
(S)-2-ETHOXY-4-(2-(METHYL-1-(2-(1-PIPERIDINYL)PHENYL)BUTYLAMINO)-2-OXOETHYL)-BENZOIC ACID
Systematic Name English
Classification Tree Code System Code
WHO-VATC QA10BD14
Created by admin on Fri Dec 15 15:52:42 GMT 2023 , Edited by admin on Fri Dec 15 15:52:42 GMT 2023
WHO-ATC A10BD14
Created by admin on Fri Dec 15 15:52:42 GMT 2023 , Edited by admin on Fri Dec 15 15:52:42 GMT 2023
NDF-RT N0000175448
Created by admin on Fri Dec 15 15:52:42 GMT 2023 , Edited by admin on Fri Dec 15 15:52:42 GMT 2023
WHO-VATC QA10BX02
Created by admin on Fri Dec 15 15:52:42 GMT 2023 , Edited by admin on Fri Dec 15 15:52:42 GMT 2023
WHO-ATC A10BX02
Created by admin on Fri Dec 15 15:52:42 GMT 2023 , Edited by admin on Fri Dec 15 15:52:42 GMT 2023
LIVERTOX NBK548879
Created by admin on Fri Dec 15 15:52:42 GMT 2023 , Edited by admin on Fri Dec 15 15:52:42 GMT 2023
NDF-RT N0000175428
Created by admin on Fri Dec 15 15:52:42 GMT 2023 , Edited by admin on Fri Dec 15 15:52:42 GMT 2023
NCI_THESAURUS C98079
Created by admin on Fri Dec 15 15:52:42 GMT 2023 , Edited by admin on Fri Dec 15 15:52:42 GMT 2023
Code System Code Type Description
PUBCHEM
65981
Created by admin on Fri Dec 15 15:52:42 GMT 2023 , Edited by admin on Fri Dec 15 15:52:42 GMT 2023
PRIMARY
ChEMBL
CHEMBL1272
Created by admin on Fri Dec 15 15:52:42 GMT 2023 , Edited by admin on Fri Dec 15 15:52:42 GMT 2023
PRIMARY
INN
6818
Created by admin on Fri Dec 15 15:52:42 GMT 2023 , Edited by admin on Fri Dec 15 15:52:42 GMT 2023
PRIMARY
DRUG CENTRAL
2366
Created by admin on Fri Dec 15 15:52:42 GMT 2023 , Edited by admin on Fri Dec 15 15:52:42 GMT 2023
PRIMARY
WIKIPEDIA
REPAGLINIDE
Created by admin on Fri Dec 15 15:52:42 GMT 2023 , Edited by admin on Fri Dec 15 15:52:42 GMT 2023
PRIMARY
LACTMED
Repaglinide
Created by admin on Fri Dec 15 15:52:42 GMT 2023 , Edited by admin on Fri Dec 15 15:52:42 GMT 2023
PRIMARY
RS_ITEM_NUM
1600813
Created by admin on Fri Dec 15 15:52:42 GMT 2023 , Edited by admin on Fri Dec 15 15:52:42 GMT 2023
PRIMARY
DAILYMED
668Z8C33LU
Created by admin on Fri Dec 15 15:52:42 GMT 2023 , Edited by admin on Fri Dec 15 15:52:42 GMT 2023
PRIMARY
SMS_ID
100000091273
Created by admin on Fri Dec 15 15:52:42 GMT 2023 , Edited by admin on Fri Dec 15 15:52:42 GMT 2023
PRIMARY
NSC
759893
Created by admin on Fri Dec 15 15:52:42 GMT 2023 , Edited by admin on Fri Dec 15 15:52:42 GMT 2023
PRIMARY
EVMPD
SUB10280MIG
Created by admin on Fri Dec 15 15:52:42 GMT 2023 , Edited by admin on Fri Dec 15 15:52:42 GMT 2023
PRIMARY
RXCUI
73044
Created by admin on Fri Dec 15 15:52:42 GMT 2023 , Edited by admin on Fri Dec 15 15:52:42 GMT 2023
PRIMARY RxNorm
FDA UNII
668Z8C33LU
Created by admin on Fri Dec 15 15:52:42 GMT 2023 , Edited by admin on Fri Dec 15 15:52:42 GMT 2023
PRIMARY
IUPHAR
6841
Created by admin on Fri Dec 15 15:52:42 GMT 2023 , Edited by admin on Fri Dec 15 15:52:42 GMT 2023
PRIMARY
DRUG BANK
DB00912
Created by admin on Fri Dec 15 15:52:42 GMT 2023 , Edited by admin on Fri Dec 15 15:52:42 GMT 2023
PRIMARY
EPA CompTox
DTXSID3023552
Created by admin on Fri Dec 15 15:52:42 GMT 2023 , Edited by admin on Fri Dec 15 15:52:42 GMT 2023
PRIMARY
CAS
135062-02-1
Created by admin on Fri Dec 15 15:52:42 GMT 2023 , Edited by admin on Fri Dec 15 15:52:42 GMT 2023
PRIMARY
USAN
KK-76
Created by admin on Fri Dec 15 15:52:42 GMT 2023 , Edited by admin on Fri Dec 15 15:52:42 GMT 2023
PRIMARY
NCI_THESAURUS
C47703
Created by admin on Fri Dec 15 15:52:42 GMT 2023 , Edited by admin on Fri Dec 15 15:52:42 GMT 2023
PRIMARY
MERCK INDEX
m9526
Created by admin on Fri Dec 15 15:52:42 GMT 2023 , Edited by admin on Fri Dec 15 15:52:42 GMT 2023
PRIMARY Merck Index
MESH
C072379
Created by admin on Fri Dec 15 15:52:42 GMT 2023 , Edited by admin on Fri Dec 15 15:52:42 GMT 2023
PRIMARY
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correction factors: for the calculation of contents, multiply the peak areas of the following impurity by the corresponding correction factor: impurity B = 0.7
CHROMATOGRAPHIC PURITY (HPLC/UV)
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correction factors: for the calculation of contents, multiply the peak areas of the following impurity by the corresponding correction factor: impurity A = 0.6
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correction factors: for the calculation of contents, multiply the peak areas of the following impurity by the corresponding correction factor: impurity C = 3.1
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