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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=CC(CC(=O)N[C@@H](CC(C)C)C2=CC=CC=C2N3CCCCC3)=CC=C1C(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
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

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
PubMed

PubMed

TitleDatePubMed
Effectiveness of nateglinide on in vitro insulin secretion from rat pancreatic islets desensitized to sulfonylureas.
2001
Glucose-dependent and glucose-sensitizing insulinotropic effect of nateglinide: comparison to sulfonylureas and repaglinide.
2001
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
Insulin secretagogues.
2002
Study of the insulinotropic effect of the novel antihyperglycemic agent KAD-1229 using HIT T15 cells, a hamster's insulinoma cell line.
2002
Control of post-prandial hyperglycemia--an essential part of good diabetes treatment and prevention of cardiovascular complications.
2002 Apr
[Differential type 2 diabetes therapy based on pathophysiological aspects].
2002 Aug
A novel simple method for the investigation of drug binding to the K(ATP) channel sulfonylurea receptor.
2002 Aug 15
High-frequency insulin pulsatility and type 2 diabetes: from physiology and pathophysiology to clinical pharmacology.
2002 Dec
Repaglinide in combination therapy.
2002 Dec
The impact of prandial glucose regulation in practice.
2002 Dec
Early-phase prandial insulin secretion: its role in the pathogenesis of type 2 diabetes mellitus and its modulation by repaglinide.
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
No effect of the novel antidiabetic agent nateglinide on the pharmacokinetics and anticoagulant properties of warfarin in healthy volunteers.
2002 Dec
Effects of S 21403 on hormone secretion from isolated rat pancreas at different glucose concentrations.
2002 Dec 5
Preventing the progressive nature of type 2 diabetes.
2002 Jul-Aug
Repaglinide: a short acting insulin secretagogue for postprandial hyperglycaemia.
2002 Jul-Sep
[Glinides and glitazones in diabetes treatment. Are they really effective?].
2002 May 2
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 (NN-623)].
2002 Sep
[Structures and mechanisms for non SU insulin secretagogues].
2002 Sep
Differential interactions of nateglinide and repaglinide on the human beta-cell sulphonylurea receptor 1.
2002 Sep
Economic model of first-line drug strategies to achieve recommended glycaemic control in newly diagnosed type 2 diabetes mellitus.
2003
Comparison between repaglinide and glimepiride in patients with type 2 diabetes mellitus: a one-year, randomized, double-blind assessment of metabolic parameters and cardiovascular risk factors.
2003 Feb
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
[symbol: see text] Nateglinide and [symbol: see text] repaglinide for type 2 diabetes?
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
Comparison of glycaemic control and cardiovascular risk profile in patients with type 2 diabetes during treatment with either repaglinide or metformin.
2003 Jun
Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics and pharmacodynamics of repaglinide: potentially hazardous interaction between gemfibrozil and repaglinide.
2003 Mar
Rationale and options for combination therapy in the treatment of Type 2 diabetes.
2003 Mar
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
Pharmacologic restoration of the early insulin response in pre-diabetic monkeys controls mealtime glucose excursions without peripheral hyperinsulinaemia.
2003 Mar
Metformin-induced hemolytic anemia in a patient with glucose-6- phosphate dehydrogenase deficiency.
2003 Mar
Safety and efficacy of repaglinide in type 2 diabetic patients with and without impaired renal function.
2003 Mar
[Differences between oral antidiabetics].
2003 Mar 20
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

In Vivo Use Guide
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
Substance Class Chemical
Created
by admin
on Mon Oct 21 22:33:03 UTC 2019
Edited
by admin
on Mon Oct 21 22:33:03 UTC 2019
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
PRANDIN
Brand Name English
REPAGLINIDE [EP]
Common Name English
REPAGLINIDE [MART.]
Common Name English
REPAGLINIDE [VANDF]
Common Name English
A10BX02
Code English
REPAGLINIDE [USP]
Common Name English
REPAGLINIDE [USAN]
Common Name English
REPAGLINIDE [WHO-DD]
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
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 Mon Oct 21 22:33:03 UTC 2019 , Edited by admin on Mon Oct 21 22:33:03 UTC 2019
WHO-ATC A10BD14
Created by admin on Mon Oct 21 22:33:03 UTC 2019 , Edited by admin on Mon Oct 21 22:33:03 UTC 2019
NDF-RT N0000175448
Created by admin on Mon Oct 21 22:33:03 UTC 2019 , Edited by admin on Mon Oct 21 22:33:03 UTC 2019
WHO-VATC QA10BX02
Created by admin on Mon Oct 21 22:33:03 UTC 2019 , Edited by admin on Mon Oct 21 22:33:03 UTC 2019
WHO-ATC A10BX02
Created by admin on Mon Oct 21 22:33:03 UTC 2019 , Edited by admin on Mon Oct 21 22:33:03 UTC 2019
LIVERTOX 840
Created by admin on Mon Oct 21 22:33:03 UTC 2019 , Edited by admin on Mon Oct 21 22:33:03 UTC 2019
NDF-RT N0000175428
Created by admin on Mon Oct 21 22:33:03 UTC 2019 , Edited by admin on Mon Oct 21 22:33:03 UTC 2019
NCI_THESAURUS C98079
Created by admin on Mon Oct 21 22:33:03 UTC 2019 , Edited by admin on Mon Oct 21 22:33:03 UTC 2019
Code System Code Type Description
PUBCHEM
65981
Created by admin on Mon Oct 21 22:33:03 UTC 2019 , Edited by admin on Mon Oct 21 22:33:03 UTC 2019
PRIMARY
ChEMBL
CHEMBL1272
Created by admin on Mon Oct 21 22:33:03 UTC 2019 , Edited by admin on Mon Oct 21 22:33:03 UTC 2019
PRIMARY
INN
6818
Created by admin on Mon Oct 21 22:33:03 UTC 2019 , Edited by admin on Mon Oct 21 22:33:03 UTC 2019
PRIMARY
LactMed
135062-02-1
Created by admin on Mon Oct 21 22:33:03 UTC 2019 , Edited by admin on Mon Oct 21 22:33:03 UTC 2019
PRIMARY
WIKIPEDIA
REPAGLINIDE
Created by admin on Mon Oct 21 22:33:03 UTC 2019 , Edited by admin on Mon Oct 21 22:33:03 UTC 2019
PRIMARY
EVMPD
SUB10280MIG
Created by admin on Mon Oct 21 22:33:03 UTC 2019 , Edited by admin on Mon Oct 21 22:33:03 UTC 2019
PRIMARY
RXCUI
73044
Created by admin on Mon Oct 21 22:33:03 UTC 2019 , Edited by admin on Mon Oct 21 22:33:03 UTC 2019
PRIMARY RxNorm
IUPHAR
6841
Created by admin on Mon Oct 21 22:33:03 UTC 2019 , Edited by admin on Mon Oct 21 22:33:03 UTC 2019
PRIMARY
DRUG BANK
DB00912
Created by admin on Mon Oct 21 22:33:03 UTC 2019 , Edited by admin on Mon Oct 21 22:33:03 UTC 2019
PRIMARY
EPA CompTox
135062-02-1
Created by admin on Mon Oct 21 22:33:03 UTC 2019 , Edited by admin on Mon Oct 21 22:33:03 UTC 2019
PRIMARY
CAS
135062-02-1
Created by admin on Mon Oct 21 22:33:03 UTC 2019 , Edited by admin on Mon Oct 21 22:33:03 UTC 2019
PRIMARY
NCI_THESAURUS
C47703
Created by admin on Mon Oct 21 22:33:03 UTC 2019 , Edited by admin on Mon Oct 21 22:33:03 UTC 2019
PRIMARY
MERCK INDEX
M9526
Created by admin on Mon Oct 21 22:33:03 UTC 2019 , Edited by admin on Mon Oct 21 22:33:03 UTC 2019
PRIMARY Merck Index
MESH
C072379
Created by admin on Mon Oct 21 22:33:03 UTC 2019 , Edited by admin on Mon Oct 21 22:33:03 UTC 2019
PRIMARY
Related Record Type Details
BASIS OF STRENGTH->SUBSTANCE
ASSAY (TITRATION)
EP
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
BASIS OF STRENGTH->SUBSTANCE
ASSAY (HPLC)
USP
TRANSPORTER -> INHIBITOR
TARGET -> INHIBITOR
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CYP2C8 and 3A4 in vitro
FECAL; PLASMA; URINE
METABOLITE INACTIVE -> PARENT
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MAJOR
FECAL
METABOLITE -> PARENT
PLASMA; URINE
Related Record Type Details
PARENT -> IMPURITY
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
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)
EP
IMPURITY -> PARENT
correction factors: for the calculation of contents, multiply the peak areas of the following impurity by the corresponding correction factor: impurity A = 0.6
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
correction factors: for the calculation of contents, multiply the peak areas of the following impurity by the corresponding correction factor: impurity C = 3.1
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Related Record Type Details
ACTIVE MOIETY