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
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
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 |
DescriptionCurator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/12196472
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.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2071 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=12196472 |
21.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Palliative | PRANDIN Approved UsePRANDIN is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Launch Date8.8274882E11 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Dose | Population | Adverse 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
AE | Significance | Dose | Population |
---|---|---|---|
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 |
PubMed
Title | Date | PubMed |
---|---|---|
Effectiveness of nateglinide on in vitro insulin secretion from rat pancreatic islets desensitized to sulfonylureas. | 2001 |
|
Oral hypoglycemic agents: insulin secretagogues, alpha-glucosidase inhibitors and insulin sensitizers. | 2001 |
|
Repaglinide and diabetes: new preparation. No better than glucose-lowering sulphonamides. | 2001 Feb |
|
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 |
|
Effect of repaglinide on cloned beta cell, cardiac and smooth muscle types of ATP-sensitive potassium channels. | 2001 Jun |
|
[Large general practice study with repaglinide. Fewer "anxiety eating" in diabetic patients]. | 2001 Mar 8 |
|
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 |
|
Interactions between antiretroviral drugs and drugs used for the therapy of the metabolic complications encountered during HIV infection. | 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 |
|
A novel simple method for the investigation of drug binding to the K(ATP) channel sulfonylurea receptor. | 2002 Aug 15 |
|
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 |
|
Oral antihyperglycemic therapy for type 2 diabetes: scientific review. | 2002 Jan 16 |
|
Preventing the progressive nature of type 2 diabetes. | 2002 Jul-Aug |
|
Current oral agents for type 2 diabetes. Many options, but which to choose when? | 2002 May |
|
[Glinides and glitazones in diabetes treatment. Are they really effective?]. | 2002 May 2 |
|
Hypoglycemia probably due to accidental intake of repaglinide. | 2002 Nov |
|
[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 |
|
Type 2 diabetes management: a comprehensive clinical review of oral medications. | 2002 Spring |
|
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 |
|
[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 |
|
Comparison of glycaemic control and cardiovascular risk profile in patients with type 2 diabetes during treatment with either repaglinide or metformin. | 2003 Jun |
|
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 |
|
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 |
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23307347
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
Edited
Wed Jul 05 23:21:09 UTC 2023
by
admin
on
Wed Jul 05 23:21:09 UTC 2023
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Record UNII |
668Z8C33LU
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Record Status |
Validated (UNII)
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Record Version |
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QA10BD14
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A10BD14
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N0000175448
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QA10BX02
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A10BX02
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NBK548879
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N0000175428
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NCI_THESAURUS |
C98079
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65981
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CHEMBL1272
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6818
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2366
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REPAGLINIDE
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Repaglinide
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1600813
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668Z8C33LU
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100000091273
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759893
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668Z8C33LU
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KK-76
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C47703
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M9526
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C072379
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Related Record | Type | Details | ||
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TRANSPORTER -> INHIBITOR | |||
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BASIS OF STRENGTH->SUBSTANCE |
ASSAY (TITRATION)
EP
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METABOLIC ENZYME -> SUBSTRATE | |||
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> INHIBITOR | |||
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BASIS OF STRENGTH->SUBSTANCE |
ASSAY (HPLC)
USP
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TRANSPORTER -> INHIBITOR | |||
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TARGET -> INHIBITOR |
Related Record | Type | Details | ||
---|---|---|---|---|
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METABOLITE -> PARENT |
CYP2C8 and 3A4 in vitro
FECAL; PLASMA; URINE
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METABOLITE INACTIVE -> PARENT |
CYP2C8 and 3A4 in vitro
MAJOR
FECAL
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METABOLITE -> PARENT |
PLASMA; URINE
|
Related Record | Type | Details | ||
---|---|---|---|---|
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PARENT -> IMPURITY |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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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
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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
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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
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Related Record | Type | Details | ||
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ACTIVE MOIETY |