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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
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ABSOLUTE
Additional Stereochemistry No
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.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
21.0 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
PRANDIN

Cmax

ValueDoseCo-administeredAnalytePopulation
65.8 ng/mL
4 mg 1 times / day multiple, oral
REPAGLINIDE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
447.4 ng × h/mL
4 mg 1 times / day multiple, oral
REPAGLINIDE plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
1.4 h
4 mg 1 times / day multiple, oral
REPAGLINIDE plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
2%
4 mg 1 times / day multiple, oral
REPAGLINIDE plasma
Homo sapiens

Doses

AEs

PubMed

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
In Vitro Use Guide
Unknown
Substance Class Chemical
Record UNII
668Z8C33LU
Record Status Validated (UNII)
Record Version