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Details

Stereochemistry ABSOLUTE
Molecular Formula C27H36N2O4
Molecular Weight 452.5868
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of REPAGLINIDE

SMILES

CCOc1cc(ccc1C(=O)O)CC(=N[C@@]([H])(CC(C)C)c2ccccc2N3CCCCC3)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 452.5868
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

8.8274882E11
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
Glucose-dependent and glucose-sensitizing insulinotropic effect of nateglinide: comparison to sulfonylureas and repaglinide.
2001
Differential effects of short and long duration insulinotropic agents on meal-related glucose excursions.
2001 Apr
[Repaglinide, potentially a therapeutic improvement for diabetes mellitus type 2].
2001 Aug 11
Repaglinide and diabetes: new preparation. No better than glucose-lowering sulphonamides.
2001 Feb
[Objectives and therapeutic strategy in type 2 diabetes mellitus].
2001 Jul
[Large general practice study with repaglinide. Fewer "anxiety eating" in diabetic patients].
2001 Mar 8
Comparison between repaglinide and glipizide in Type 2 diabetes mellitus: a 1-year multicentre study.
2001 May
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
Effect of repaglinide addition to NPH insulin monotherapy on glycemic control in patients with type 2 diabetes.
2001 Oct
[New drugs].
2001 Sep
Repaglinide improves blood glucose control in sulphonylurea-naive type 2 diabetes.
2001 Sep
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
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
Clinical pharmacokinetics and pharmacodynamics of repaglinide.
2002
Control of post-prandial hyperglycemia--an essential part of good diabetes treatment and prevention of cardiovascular complications.
2002 Apr
[Postprandial hyperglycemia. II. Pharmacological approaches].
2002 Apr
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
Optimizing insulin secretagogue therapy in patients with type 2 diabetes: a randomized double-blind study with repaglinide.
2002 Feb
Type 2 diabetes management.
2002 Jan
Gateways to clinical trials.
2002 Jan-Feb
Repaglinide: a short acting insulin secretagogue for postprandial hyperglycaemia.
2002 Jul-Sep
Current oral agents for type 2 diabetes. Many options, but which to choose when?
2002 May
Repaglinide versus metformin in combination with bedtime NPH insulin in patients with type 2 diabetes established on insulin/metformin combination therapy.
2002 Oct
[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
Rationale and options for combination therapy in the treatment of Type 2 diabetes.
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
Lack of effect of acute repaglinide administration on postprandial lipaemia in patients with type 2 diabetes mellitus.
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 Jun 25 21:00:29 UTC 2021
Edited
by admin
on Fri Jun 25 21:00:29 UTC 2021
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
A10BX02
Code 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
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 Jun 25 21:00:29 UTC 2021 , Edited by admin on Fri Jun 25 21:00:29 UTC 2021
WHO-ATC A10BD14
Created by admin on Fri Jun 25 21:00:29 UTC 2021 , Edited by admin on Fri Jun 25 21:00:29 UTC 2021
NDF-RT N0000175448
Created by admin on Fri Jun 25 21:00:29 UTC 2021 , Edited by admin on Fri Jun 25 21:00:29 UTC 2021
WHO-VATC QA10BX02
Created by admin on Fri Jun 25 21:00:29 UTC 2021 , Edited by admin on Fri Jun 25 21:00:29 UTC 2021
WHO-ATC A10BX02
Created by admin on Fri Jun 25 21:00:29 UTC 2021 , Edited by admin on Fri Jun 25 21:00:29 UTC 2021
LIVERTOX 840
Created by admin on Fri Jun 25 21:00:29 UTC 2021 , Edited by admin on Fri Jun 25 21:00:29 UTC 2021
NDF-RT N0000175428
Created by admin on Fri Jun 25 21:00:29 UTC 2021 , Edited by admin on Fri Jun 25 21:00:29 UTC 2021
NCI_THESAURUS C98079
Created by admin on Fri Jun 25 21:00:29 UTC 2021 , Edited by admin on Fri Jun 25 21:00:29 UTC 2021
Code System Code Type Description
USP_CATALOG
1600813
Created by admin on Fri Jun 25 21:00:29 UTC 2021 , Edited by admin on Fri Jun 25 21:00:29 UTC 2021
PRIMARY USP-RS
PUBCHEM
65981
Created by admin on Fri Jun 25 21:00:29 UTC 2021 , Edited by admin on Fri Jun 25 21:00:29 UTC 2021
PRIMARY
ChEMBL
CHEMBL1272
Created by admin on Fri Jun 25 21:00:29 UTC 2021 , Edited by admin on Fri Jun 25 21:00:29 UTC 2021
PRIMARY
INN
6818
Created by admin on Fri Jun 25 21:00:29 UTC 2021 , Edited by admin on Fri Jun 25 21:00:29 UTC 2021
PRIMARY
DRUG CENTRAL
2366
Created by admin on Fri Jun 25 21:00:29 UTC 2021 , Edited by admin on Fri Jun 25 21:00:29 UTC 2021
PRIMARY
WIKIPEDIA
REPAGLINIDE
Created by admin on Fri Jun 25 21:00:29 UTC 2021 , Edited by admin on Fri Jun 25 21:00:29 UTC 2021
PRIMARY
LACTMED
Repaglinide
Created by admin on Fri Jun 25 21:00:29 UTC 2021 , Edited by admin on Fri Jun 25 21:00:29 UTC 2021
PRIMARY
EVMPD
SUB10280MIG
Created by admin on Fri Jun 25 21:00:29 UTC 2021 , Edited by admin on Fri Jun 25 21:00:29 UTC 2021
PRIMARY
RXCUI
73044
Created by admin on Fri Jun 25 21:00:29 UTC 2021 , Edited by admin on Fri Jun 25 21:00:29 UTC 2021
PRIMARY RxNorm
FDA UNII
668Z8C33LU
Created by admin on Fri Jun 25 21:00:29 UTC 2021 , Edited by admin on Fri Jun 25 21:00:29 UTC 2021
PRIMARY
IUPHAR
6841
Created by admin on Fri Jun 25 21:00:29 UTC 2021 , Edited by admin on Fri Jun 25 21:00:29 UTC 2021
PRIMARY
DRUG BANK
DB00912
Created by admin on Fri Jun 25 21:00:29 UTC 2021 , Edited by admin on Fri Jun 25 21:00:29 UTC 2021
PRIMARY
EPA CompTox
135062-02-1
Created by admin on Fri Jun 25 21:00:29 UTC 2021 , Edited by admin on Fri Jun 25 21:00:29 UTC 2021
PRIMARY
CAS
135062-02-1
Created by admin on Fri Jun 25 21:00:29 UTC 2021 , Edited by admin on Fri Jun 25 21:00:29 UTC 2021
PRIMARY
NCI_THESAURUS
C47703
Created by admin on Fri Jun 25 21:00:29 UTC 2021 , Edited by admin on Fri Jun 25 21:00:29 UTC 2021
PRIMARY
MERCK INDEX
M9526
Created by admin on Fri Jun 25 21:00:29 UTC 2021 , Edited by admin on Fri Jun 25 21:00:29 UTC 2021
PRIMARY Merck Index
MESH
C072379
Created by admin on Fri Jun 25 21:00:29 UTC 2021 , Edited by admin on Fri Jun 25 21:00:29 UTC 2021
PRIMARY
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