Identification

Name
Repaglinide
Accession Number
DB00912  (APRD00439)
Type
Small Molecule
Groups
Approved, Investigational
Description

Repaglinide is an oral antihyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus (NIDDM). It belongs to the meglitinide class of short-acting insulin secretagogues, which act by binding to β cells of the pancreas to stimulate insulin release. Repaglinide induces an early insulin response to meals decreasing postprandial blood glucose levels. It should only be taken with meals and meal-time doses should be skipped with any skipped meal. Approximately one month of therapy is required before a decrease in fasting blood glucose is seen. Meglitnides may have a neutral effect on weight or cause a slight increase in weight. The average weight gain caused by meglitinides appears to be lower than that caused by sulfonylureas and insulin and appears to occur only in those naïve to oral antidiabetic agents. Due to their mechanism of action, meglitinides may cause hypoglycemia although the risk is thought to be lower than that of sulfonylureas since their action is dependent on the presence of glucose. In addition to reducing postprandial and fasting blood glucose, meglitnides have been shown to decrease glycosylated hemoglobin (HbA1c) levels, which are reflective of the last 8-10 weeks of glucose control. Meglitinides appear to be more effective at lowering postprandial blood glucose than metformin, sulfonylureas and thiazolidinediones. Repaglinide is extensively metabolized in the liver and excreted in bile. Repaglinide metabolites do not possess appreciable hypoglycemic activity. Approximately 90% of a single orally administered dose is eliminated in feces and 8% in urine.

Structure
Thumb
Synonyms
  • AG-EE 388 ZW
  • AG-EE 623 ZW
  • Repaglinida
  • Repaglinidum
  • Surepost
External IDs
A10BX02 / AG-EE-623ZW
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act RepaglinideTablet0.5 mgOralActavis Pharma Company2010-10-18Not applicableCanada
Act RepaglinideTablet2 mgOralActavis Pharma Company2010-10-18Not applicableCanada
Act RepaglinideTablet1 mgOralActavis Pharma Company2010-10-18Not applicableCanada
Gluconorm 0.5mgTablet0.5 mgOralNovo Nordisk1999-06-21Not applicableCanada
Gluconorm 1.0mgTablet1.0 mgOralNovo Nordisk1999-06-21Not applicableCanada
Gluconorm 2.0mgTablet2.0 mgOralNovo Nordisk1999-06-21Not applicableCanada
NovonormTablet1 mgOralNovo Nordisk1998-08-17Not applicableEu
NovonormTablet2 mgOralNovo Nordisk1998-08-17Not applicableEu
NovonormTablet1 mgOralNovo Nordisk1998-08-17Not applicableEu
NovonormTablet2 mgOralNovo Nordisk1998-08-17Not applicableEu
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-repaglinideTablet0.5 mgOralApotex Corporation2012-10-16Not applicableCanada
Apo-repaglinideTablet2.0 mgOralApotex Corporation2012-10-16Not applicableCanada
Apo-repaglinideTablet1.0 mgOralApotex Corporation2012-10-16Not applicableCanada
Auro-repaglinideTablet2 mgOralAuro Pharma Inc2014-04-30Not applicableCanada
Auro-repaglinideTablet1 mgOralAuro Pharma Inc2014-04-30Not applicableCanada
Auro-repaglinideTablet0.5 mgOralAuro Pharma Inc2014-04-30Not applicableCanada
EnyglidTablet0.5 mgOralKrka, D.D., Novo Mesto2009-10-14Not applicableEu
EnyglidTablet2 mgOralKrka, D.D., Novo Mesto2009-10-14Not applicableEu
EnyglidTablet2 mgOralKrka, D.D., Novo Mesto2009-10-14Not applicableEu
EnyglidTablet1 mgOralKrka, D.D., Novo Mesto2009-10-14Not applicableEu
International/Other Brands
GlucoNorm (Novo Nordisk) / Prandin
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
PrandiMetRepaglinide (2 mg/1) + Metformin Hydrochloride (500 mg/1)TabletOralNovo Nordisk2009-01-152017-06-02Us
PrandiMetRepaglinide (1 mg/1) + Metformin Hydrochloride (500 mg/1)TabletOralNovo Nordisk2009-01-162017-06-02Us
Repaglinide and Metformin HydrochlorideRepaglinide (1 mg/1) + Metformin Hydrochloride (500 mg/1)TabletOralLupin Pharmaceuticals2015-12-10Not applicableUs
Repaglinide and Metformin HydrochlorideRepaglinide (2 mg/1) + Metformin Hydrochloride (500 mg/1)TabletOralLupin Pharmaceuticals2015-12-10Not applicableUs
Categories
UNII
668Z8C33LU
CAS number
135062-02-1
Weight
Average: 452.5857
Monoisotopic: 452.26750765
Chemical Formula
C27H36N2O4
InChI Key
FAEKWTJYAYMJKF-QHCPKHFHSA-N
InChI
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
IUPAC Name
2-ethoxy-4-({[(1S)-3-methyl-1-[2-(piperidin-1-yl)phenyl]butyl]carbamoyl}methyl)benzoic acid
SMILES
CCOC1=C(C=CC(CC(=O)N[[email protected]@H](CC(C)C)C2=CC=CC=C2N2CCCCC2)=C1)C(O)=O

Pharmacology

Indication

As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Structured Indications
Pharmacodynamics

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. When extracellular glucose concentrations are low, ATP-sensitive potassium channels open causing membrane repolarization. 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 increases insulin release by inhibiting ATP-sensitive potassium channels in a glucose-dependent manner.

Mechanism of action

Repaglinide activity is dependent on the presence functioning β cells and glucose. In contrast to sulfonylurea insulin secretatogogues, repaglinide has no effect on insulin release in the absence of glucose. Rather, it potentiates the effect of extracellular glucose on ATP-sensitive potassium channel and has little effect on insulin levels between meals and overnight. As such, repaglinide is more effective at reducing postprandial blood glucose levels than fasting blood glucose levels and requires a longer duration of therapy (approximately one month) before decreases in fasting blood glucose are observed. The insulinotropic effects of repaglinide are highest at intermediate glucose levels (3 to 10 mmol/L) and it does not increase insulin release already stimulated by high glucose concentrations (greater than 15 mmol/L). Repaglinide appears to be selective for pancreatic β cells and does not appear to affect skeletal or cardiac muscle or thyroid tissue.

TargetActionsOrganism
AATP-binding cassette sub-family C member 8
inhibitor
Human
UPeroxisome proliferator-activated receptor gamma
agonist
Human
Absorption

Rapidly and completely absorbed following oral administration. Peak plasma concentrations are observed within 1 hour (range 0.5-1.4 hours). The absolute bioavailability is approximately 56%. Maximal biological effect is observed within 3-3.5 hours and plasma insulin levels remain elevated for 4-6 hours. When a single 2 mg dose of repaglinide is given to healthy subjects, the area under the curve (AUC) is 18.0 - 18.7 (ng/mL/h)^3.

Volume of distribution

31 L following IV administration in healthy individuals

Protein binding

>98% (e.g. to to albumin and α1-acid glycoprotein)

Metabolism

Repaglinide is rapidly metabolized via oxidation and dealkylation by cytochrome P450 3A4 and 2C9 to form the major dicarboxylic acid derivative (M2). Further oxidation produces the aromatic amine derivative (M1). Glucuronidation of the carboxylic acid group of repaglinide yields an acyl glucuronide (M7). Several other unidentified metabolites have been detected. Repaglinide metabolites to not possess appreciable hypoglycemic activity.

Route of elimination

90% eliminated in feces (<2% as unchanged drug), 8% in urine (0.1% as unchanged drug)

Half life

1 hour

Clearance

33-38 L/hour following IV administration

Toxicity

LD50 >1 g/kg (rat) (W. Grell)

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Repaglinide Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbirateroneThe serum concentration of Repaglinide can be increased when it is combined with Abiraterone.Approved
AmiodaroneThe serum concentration of Repaglinide can be increased when it is combined with Amiodarone.Approved, Investigational
AprepitantThe serum concentration of Repaglinide can be increased when it is combined with Aprepitant.Approved, Investigational
AtazanavirThe serum concentration of Repaglinide can be increased when it is combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Repaglinide can be decreased when combined with Atomoxetine.Approved
AtorvastatinThe risk or severity of adverse effects can be increased when Repaglinide is combined with Atorvastatin.Approved
BendroflumethiazideThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Bendroflumethiazide.Approved
BoceprevirThe serum concentration of Repaglinide can be increased when it is combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Repaglinide can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Repaglinide can be decreased when it is combined with Bosentan.Approved, Investigational
BosutinibThe serum concentration of Bosutinib can be increased when it is combined with Repaglinide.Approved
BromocriptineThe risk or severity of adverse effects can be increased when Bromocriptine is combined with Repaglinide.Approved, Investigational
CabergolineThe risk or severity of adverse effects can be increased when Cabergoline is combined with Repaglinide.Approved
CarbamazepineThe metabolism of Repaglinide can be increased when combined with Carbamazepine.Approved, Investigational
CarbomycinThe serum concentration of Repaglinide can be increased when it is combined with Carbomycin.Vet Approved
CelecoxibThe metabolism of Repaglinide can be decreased when combined with Celecoxib.Approved, Investigational
CeritinibThe serum concentration of Repaglinide can be increased when it is combined with Ceritinib.Approved
CerivastatinThe serum concentration of Cerivastatin can be increased when it is combined with Repaglinide.Withdrawn
ChlorothiazideThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Chlorothiazide.Approved, Vet Approved
ChlorthalidoneThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Chlorthalidone.Approved
ClarithromycinThe serum concentration of Repaglinide can be increased when it is combined with Clarithromycin.Approved
ClemastineThe metabolism of Repaglinide can be decreased when combined with Clemastine.Approved
ClopidogrelThe serum concentration of Repaglinide can be increased when it is combined with Clopidogrel.Approved
ClotrimazoleThe metabolism of Repaglinide can be decreased when combined with Clotrimazole.Approved, Vet Approved
CobicistatThe serum concentration of Repaglinide can be increased when it is combined with Cobicistat.Approved
ConivaptanThe serum concentration of Conivaptan can be increased when it is combined with Repaglinide.Approved, Investigational
CrisaboroleThe metabolism of Repaglinide can be decreased when combined with Crisaborole.Approved, Investigational
CrizotinibThe metabolism of Repaglinide can be decreased when combined with Crizotinib.Approved
CyclopenthiazideThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Cyclopenthiazide.Experimental
CyclosporineThe serum concentration of Repaglinide can be increased when it is combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Repaglinide can be decreased when it is combined with Dabrafenib.Approved
DarunavirThe serum concentration of Repaglinide can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Repaglinide can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Repaglinide can be increased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Repaglinide can be decreased when combined with Delavirdine.Approved
DihydroergocornineThe risk or severity of adverse effects can be increased when Dihydroergocornine is combined with Repaglinide.Approved
DihydroergocristineThe risk or severity of adverse effects can be increased when Dihydroergocristine is combined with Repaglinide.Approved, Experimental
DihydroergocryptineThe risk or severity of adverse effects can be increased when Dihydroergocryptine is combined with Repaglinide.Experimental
DihydroergotamineThe metabolism of Repaglinide can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Repaglinide can be decreased when combined with Diltiazem.Approved
DoxycyclineThe metabolism of Repaglinide can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Repaglinide can be decreased when combined with Dronedarone.Approved
EfavirenzThe metabolism of Repaglinide can be decreased when combined with Efavirenz.Approved, Investigational
EltrombopagThe serum concentration of Repaglinide can be increased when it is combined with Eltrombopag.Approved
EnzalutamideThe serum concentration of Repaglinide can be decreased when it is combined with Enzalutamide.Approved
ErgonovineThe risk or severity of adverse effects can be increased when Ergonovine is combined with Repaglinide.Approved
ErgotamineThe risk or severity of adverse effects can be increased when Ergotamine is combined with Repaglinide.Approved
ErtugliflozinErtugliflozin may increase the hypoglycemic activities of Repaglinide.Approved
ErythromycinThe serum concentration of Repaglinide can be increased when it is combined with Erythromycin.Approved, Vet Approved
FelodipineThe metabolism of Repaglinide can be decreased when combined with Felodipine.Approved, Investigational
FluconazoleThe metabolism of Repaglinide can be decreased when combined with Fluconazole.Approved
FluvastatinThe serum concentration of Fluvastatin can be increased when it is combined with Repaglinide.Approved
FluvoxamineThe metabolism of Repaglinide can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Repaglinide can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Repaglinide can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Repaglinide can be increased when combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Repaglinide can be increased when it is combined with Fusidic Acid.Approved
GemfibrozilThe serum concentration of Repaglinide can be increased when it is combined with Gemfibrozil.Approved
HydrochlorothiazideThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Hydrochlorothiazide.Approved, Vet Approved
HydroflumethiazideThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Hydroflumethiazide.Approved, Investigational
IbrutinibThe serum concentration of Ibrutinib can be increased when it is combined with Repaglinide.Approved
IdelalisibThe serum concentration of Repaglinide can be increased when it is combined with Idelalisib.Approved
ImatinibThe metabolism of Repaglinide can be decreased when combined with Imatinib.Approved
IndapamideThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Indapamide.Approved
IndinavirThe serum concentration of Repaglinide can be increased when it is combined with Indinavir.Approved
IrbesartanThe metabolism of Repaglinide can be decreased when combined with Irbesartan.Approved, Investigational
IsavuconazoniumThe metabolism of Repaglinide can be decreased when combined with Isavuconazonium.Approved, Investigational
IsradipineThe metabolism of Repaglinide can be decreased when combined with Isradipine.Approved
ItraconazoleThe serum concentration of Repaglinide can be increased when it is combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Repaglinide can be increased when it is combined with Ivacaftor.Approved
JosamycinThe serum concentration of Repaglinide can be increased when it is combined with Josamycin.Approved, Investigational
KetoconazoleThe serum concentration of Repaglinide can be increased when it is combined with Ketoconazole.Approved, Investigational
KitasamycinThe serum concentration of Repaglinide can be increased when it is combined with Kitasamycin.Experimental
LapatinibThe metabolism of Repaglinide can be decreased when combined with Lapatinib.Approved, Investigational
Lipoic AcidLipoic Acid may increase the hypoglycemic activities of Repaglinide.Approved, Nutraceutical
LisurideThe risk or severity of adverse effects can be increased when Lisuride is combined with Repaglinide.Approved, Investigational
LopinavirThe serum concentration of Repaglinide can be increased when it is combined with Lopinavir.Approved
LorpiprazoleThe serum concentration of Repaglinide can be increased when it is combined with Lorpiprazole.Approved
LosartanThe metabolism of Repaglinide can be decreased when combined with Losartan.Approved
LovastatinThe metabolism of Repaglinide can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Repaglinide can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Repaglinide can be increased when it is combined with Lumacaftor.Approved
Lysergic Acid DiethylamideThe risk or severity of adverse effects can be increased when Lysergic Acid Diethylamide is combined with Repaglinide.Illicit, Investigational, Withdrawn
MedrogestoneThe serum concentration of Repaglinide can be decreased when it is combined with Medrogestone.Approved
MetergolineThe risk or severity of adverse effects can be increased when Metergoline is combined with Repaglinide.Experimental
MethyclothiazideThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Methyclothiazide.Approved
MethylergometrineThe risk or severity of adverse effects can be increased when Methylergometrine is combined with Repaglinide.Approved
MethysergideThe risk or severity of adverse effects can be increased when Methysergide is combined with Repaglinide.Approved
MetolazoneThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Metolazone.Approved
MevastatinThe serum concentration of Mevastatin can be increased when it is combined with Repaglinide.Experimental
MifepristoneThe serum concentration of Repaglinide can be increased when it is combined with Mifepristone.Approved, Investigational
MitotaneThe serum concentration of Repaglinide can be decreased when it is combined with Mitotane.Approved
NefazodoneThe serum concentration of Repaglinide can be increased when it is combined with Nefazodone.Approved, Withdrawn
NelfinavirThe serum concentration of Repaglinide can be increased when it is combined with Nelfinavir.Approved
NetupitantThe serum concentration of Repaglinide can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Repaglinide can be increased when combined with Nevirapine.Approved
NicergolineThe risk or severity of adverse effects can be increased when Nicergoline is combined with Repaglinide.Approved, Investigational
NilotinibThe metabolism of Repaglinide can be decreased when combined with Nilotinib.Approved, Investigational
OlaparibThe metabolism of Repaglinide can be decreased when combined with Olaparib.Approved
OleandomycinThe serum concentration of Repaglinide can be increased when it is combined with Oleandomycin.Vet Approved
OsimertinibThe serum concentration of Repaglinide can be increased when it is combined with Osimertinib.Approved
PalbociclibThe serum concentration of Repaglinide can be increased when it is combined with Palbociclib.Approved
PentobarbitalThe metabolism of Repaglinide can be increased when combined with Pentobarbital.Approved, Vet Approved
PergolideThe risk or severity of adverse effects can be increased when Pergolide is combined with Repaglinide.Approved, Investigational, Vet Approved, Withdrawn
PhenobarbitalThe metabolism of Repaglinide can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Repaglinide can be increased when combined with Phenytoin.Approved, Vet Approved
PioglitazoneThe metabolism of Repaglinide can be decreased when combined with Pioglitazone.Approved, Investigational
PitavastatinThe serum concentration of Pitavastatin can be increased when it is combined with Repaglinide.Approved
PolythiazideThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Polythiazide.Approved
PosaconazoleThe serum concentration of Repaglinide can be increased when it is combined with Posaconazole.Approved, Investigational, Vet Approved
PravastatinThe serum concentration of Pravastatin can be increased when it is combined with Repaglinide.Approved
PregabalinThe risk or severity of heart failure can be increased when Pregabalin is combined with Repaglinide.Approved, Illicit, Investigational
PrimidoneThe metabolism of Repaglinide can be increased when combined with Primidone.Approved, Vet Approved
QuinethazoneThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Quinethazone.Approved
QuinineThe metabolism of Repaglinide can be decreased when combined with Quinine.Approved
RabeprazoleThe metabolism of Repaglinide can be decreased when combined with Rabeprazole.Approved, Investigational
RanolazineThe metabolism of Repaglinide can be decreased when combined with Ranolazine.Approved, Investigational
RifabutinThe metabolism of Repaglinide can be increased when combined with Rifabutin.Approved
RifampicinThe serum concentration of Repaglinide can be decreased when it is combined with Rifampicin.Approved
RifapentineThe metabolism of Repaglinide can be increased when combined with Rifapentine.Approved
RilpivirineThe serum concentration of Rilpivirine can be increased when it is combined with Repaglinide.Approved
RosiglitazoneThe metabolism of Repaglinide can be decreased when combined with Rosiglitazone.Approved, Investigational
RosuvastatinThe serum concentration of Rosuvastatin can be increased when it is combined with Repaglinide.Approved
RucaparibThe metabolism of Repaglinide can be decreased when combined with Rucaparib.Approved, Investigational
SaquinavirThe serum concentration of Repaglinide can be increased when it is combined with Saquinavir.Approved, Investigational
SarilumabThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Sarilumab.Approved
SecobarbitalThe metabolism of Repaglinide can be increased when combined with Secobarbital.Approved, Vet Approved
SildenafilThe metabolism of Repaglinide can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Repaglinide can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Repaglinide can be increased when it is combined with Simeprevir.Approved
SimvastatinThe serum concentration of Simvastatin can be increased when it is combined with Repaglinide.Approved
SolithromycinThe serum concentration of Repaglinide can be increased when it is combined with Solithromycin.Investigational
St. John's WortThe serum concentration of Repaglinide can be decreased when it is combined with St. John's Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Repaglinide can be increased when it is combined with Stiripentol.Approved
SulfamethoxazoleThe metabolism of Repaglinide can be decreased when combined with Sulfamethoxazole.Approved
SulfisoxazoleThe metabolism of Repaglinide can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TamoxifenThe metabolism of Repaglinide can be decreased when combined with Tamoxifen.Approved
TelaprevirThe serum concentration of Repaglinide can be increased when it is combined with Telaprevir.Approved, Withdrawn
TelithromycinThe serum concentration of Repaglinide can be increased when it is combined with Telithromycin.Approved
TergurideThe risk or severity of adverse effects can be increased when Terguride is combined with Repaglinide.Experimental
TeriflunomideThe serum concentration of Repaglinide can be increased when it is combined with Teriflunomide.Approved
TiclopidineThe metabolism of Repaglinide can be decreased when combined with Ticlopidine.Approved
TocilizumabThe serum concentration of Repaglinide can be decreased when it is combined with Tocilizumab.Approved
TolvaptanThe serum concentration of Tolvaptan can be increased when it is combined with Repaglinide.Approved
TopiroxostatThe metabolism of Repaglinide can be decreased when combined with Topiroxostat.Approved, Investigational
TrichlormethiazideThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Trichlormethiazide.Approved, Vet Approved
TrimethoprimThe metabolism of Repaglinide can be decreased when combined with Trimethoprim.Approved, Vet Approved
TylosinThe serum concentration of Repaglinide can be increased when it is combined with Tylosin.Vet Approved
UbidecarenoneThe therapeutic efficacy of Repaglinide can be increased when used in combination with Ubidecarenone.Approved, Investigational, Nutraceutical
VemurafenibThe serum concentration of Repaglinide can be decreased when it is combined with Vemurafenib.Approved
VenlafaxineThe metabolism of Repaglinide can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Repaglinide can be decreased when combined with Verapamil.Approved
VoriconazoleThe serum concentration of Repaglinide can be increased when it is combined with Voriconazole.Approved, Investigational
ZiprasidoneThe metabolism of Repaglinide can be decreased when combined with Ziprasidone.Approved
Food Interactions
  • Take up to 30 minutes before meals.
  • When taken with a high-fat meal, AUC and Cmax decreases.

References

Synthesis Reference

Manne Reddy, "Polymorphic forms of (S)-Repaglinide and the processes for preparation thereof." U.S. Patent US20040102477, issued May 27, 2004.

US20040102477
General References
  1. Massi-Benedetti M, Damsbo P: Pharmacology and clinical experience with repaglinide. Expert Opin Investig Drugs. 2000 Apr;9(4):885-98. [PubMed:11060717]
External Links
Human Metabolome Database
HMDB0015048
KEGG Drug
D00594
KEGG Compound
C07670
PubChem Compound
65981
PubChem Substance
46508150
ChemSpider
59377
BindingDB
50153520
ChEBI
8805
ChEMBL
CHEMBL1272
Therapeutic Targets Database
DAP000133
PharmGKB
PA451234
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Repaglinide
ATC Codes
A10BD14 — Metformin and repaglinideA10BX02 — Repaglinide
AHFS Codes
  • 68:20.16 — Meglitinides
FDA label
Download (175 KB)
MSDS
Download (57.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceDrug-Drug Interaction (DDI) / Healthy Volunteers1
1CompletedBasic ScienceHealthy Volunteers / Pharmacokinetics of Caffeine / Pharmacokinetics of Repaglinide1
1CompletedTreatmentDiabetes Mellitus (DM) / Healthy Volunteers1
1CompletedTreatmentDiabetes Mellitus (DM) / Type 2 Diabetes Mellitus2
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentParkinson's Disease (PD)1
1RecruitingTreatmentAdvanced Solid Tumors / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Mantle Cell Lymphoma (MCL) / Marginal Zone Lymphoma / Primary Mediastinal Lymphoma1
2CompletedTreatmentType 2 Diabetes Mellitus1
3CompletedPreventionAtherosclerosis / Cardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Diabetes Mellitus (DM) / High Blood Cholesterol Level / High Blood Pressure (Hypertension) / Type 2 Diabetes Mellitus1
3CompletedTreatmentCystic Fibrosis (CF) / Diabetes Mellitus (DM)2
3CompletedTreatmentDiabetes Mellitus (DM) / Type 2 Diabetes Mellitus2
4CompletedTreatmentDiabetes Mellitus (DM) / Type 2 Diabetes Mellitus10
4CompletedTreatmentType 2 Diabetes Mellitus4
4Not Yet RecruitingTreatmentType 2 Diabetes Mellitus1
4RecruitingTreatmentType 2 Diabetes Mellitus1
4TerminatedTreatmentDiabetes Mellitus (DM) / Type 2 Diabetes Mellitus1
4Unknown StatusTreatmentType 2 Diabetes Mellitus1
Not AvailableActive Not RecruitingTreatmentDiabetes Mellitus (DM)1
Not AvailableCompletedNot AvailableCystic Fibrosis Related Diabetes / Pancreatic Insufficiency1
Not AvailableCompletedNot AvailableDiabetes Mellitus (DM) / Type 2 Diabetes Mellitus6
Not AvailableCompletedNot AvailableType 2 Diabetes Mellitus3
Not AvailableUnknown StatusNot AvailableType 2 Diabetes Mellitus1
Not AvailableWithdrawnTreatmentDiabetes Mellitus (DM)1

Pharmacoeconomics

Manufacturers
  • Novo nordisk inc
  • Novo Nordisk Inc.
Packagers
Dosage forms
FormRouteStrength
TabletOral1 mg
TabletOral2 mg
TabletOral0.5 mg
TabletOral1.0 mg
TabletOral2.0 mg
TabletOral
TabletOral.5 mg/1
TabletOral1 mg/mg
TabletOral2 mg/mg
TabletOral1 mg/1
TabletOral2 mg/1
TabletOral5 mg
Prices
Unit descriptionCostUnit
Prandin 1 mg tablet2.48USD tablet
Prandin 0.5 mg tablet2.47USD tablet
Prandin 2 mg tablet2.33USD tablet
Gluconorm 2 mg Tablet0.34USD tablet
Gluconorm 1 mg Tablet0.32USD tablet
Gluconorm 0.5 mg Tablet0.31USD tablet
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Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6677358No1998-06-122018-06-12Us
CA2111851No2002-02-262011-06-21Canada

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)130-131 °CNot Available
logP5.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00294 mg/mLALOGPS
logP5.05ALOGPS
logP3.95ChemAxon
logS-5.2ALOGPS
pKa (Strongest Acidic)3.68ChemAxon
pKa (Strongest Basic)4.82ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area78.87 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity131.83 m3·mol-1ChemAxon
Polarizability51.49 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9172
Blood Brain Barrier-0.7101
Caco-2 permeable-0.5891
P-glycoprotein substrateSubstrate0.8145
P-glycoprotein inhibitor IInhibitor0.6044
P-glycoprotein inhibitor IIInhibitor0.6868
Renal organic cation transporterNon-inhibitor0.849
CYP450 2C9 substrateNon-substrate0.8288
CYP450 2D6 substrateNon-substrate0.9117
CYP450 3A4 substrateSubstrate0.7019
CYP450 1A2 substrateNon-inhibitor0.9206
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.9264
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8682
Ames testNon AMES toxic0.8136
CarcinogenicityNon-carcinogens0.8004
BiodegradationNot ready biodegradable0.919
Rat acute toxicity2.4497 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9605
hERG inhibition (predictor II)Non-inhibitor0.5272
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-0udi-0000900000-c0108433e6c3f3bf1c75
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-004i-0009000000-30aa31031f07d8ae52b8
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-002r-0908000000-b76282b9697187110f0a
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0udi-0000900000-2f6de321d96a7df0cde9
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0udi-0140900000-4fef8b8042e88aa84955
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-001i-0290000000-4867f74dff429e78bb45
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-001i-0290000000-bdb018b622ca04e9d8b1
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-001i-0590000000-60f613e4ee0d364efcea
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0f89-2791700000-333192fa8176a2febaa5

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenylpiperidines. These are compounds containing a phenylpiperidine skeleton, which consists of a piperidine bound to a phenyl group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Piperidines
Sub Class
Phenylpiperidines
Direct Parent
Phenylpiperidines
Alternative Parents
Phenylacetamides / Benzoic acids / Aniline and substituted anilines / Benzoyl derivatives / Dialkylarylamines / Phenol ethers / Phenoxy compounds / Alkyl aryl ethers / Amino acids / Secondary carboxylic acid amides
show 7 more
Substituents
Phenylpiperidine / Phenylacetamide / Benzoic acid or derivatives / Benzoic acid / Phenoxy compound / Benzoyl / Phenol ether / Tertiary aliphatic/aromatic amine / Dialkylarylamine / Aniline or substituted anilines
show 23 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
piperidines (CHEBI:8805)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Sulfonylurea receptor activity
Specific Function
Subunit of the beta-cell ATP-sensitive potassium channel (KATP). Regulator of ATP-sensitive K(+) channels and insulin release.
Gene Name
ABCC8
Uniprot ID
Q09428
Uniprot Name
ATP-binding cassette sub-family C member 8
Molecular Weight
176990.36 Da
References
  1. Hu S, Wang S, Fanelli B, Bell PA, Dunning BE, Geisse S, Schmitz R, Boettcher BR: Pancreatic beta-cell K(ATP) channel activity and membrane-binding studies with nateglinide: A comparison with sulfonylureas and repaglinide. J Pharmacol Exp Ther. 2000 May;293(2):444-52. [PubMed:10773014]
  2. Sunaga Y, Gonoi T, Shibasaki T, Ichikawa K, Kusama H, Yano H, Seino S: 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. Eur J Pharmacol. 2001 Nov 9;431(1):119-25. [PubMed:11716850]
  3. Hansen AM, Christensen IT, Hansen JB, Carr RD, Ashcroft FM, Wahl P: Differential interactions of nateglinide and repaglinide on the human beta-cell sulphonylurea receptor 1. Diabetes. 2002 Sep;51(9):2789-95. [PubMed:12196472]
  4. Wangler B, Schneider S, Thews O, Schirrmacher E, Comagic S, Feilen P, Schwanstecher C, Schwanstecher M, Shiue CY, Alavi A, Hohnemann S, Piel M, Rosch F, Schirrmacher R: Synthesis and evaluation of (S)-2-(2-[18F]fluoroethoxy)-4-([3-methyl-1-(2-piperidin-1-yl-phenyl)-butyl-carbam oyl]-methyl)-benzoic acid ([18F]repaglinide): a promising radioligand for quantification of pancreatic beta-cell mass with positron emission tomography (PET). Nucl Med Biol. 2004 Jul;31(5):639-47. [PubMed:15219283]
  5. Wangler B, Beck C, Shiue CY, Schneider S, Schwanstecher C, Schwanstecher M, Feilen PJ, Alavi A, Rosch F, Schirrmacher R: Synthesis and in vitro evaluation of (S)-2-([11C]methoxy)-4-[3-methyl-1-(2-piperidine-1-yl-phenyl)-butyl-carbamoyl]-be nzoic acid ([11C]methoxy-repaglinide): a potential beta-cell imaging agent. Bioorg Med Chem Lett. 2004 Oct 18;14(20):5205-9. [PubMed:15380228]
  6. Dornhorst A: Insulinotropic meglitinide analogues. Lancet. 2001 Nov 17;358(9294):1709-16. [PubMed:11728565]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE...
Gene Name
PPARG
Uniprot ID
P37231
Uniprot Name
Peroxisome proliferator-activated receptor gamma
Molecular Weight
57619.58 Da
References
  1. Scarsi M, Podvinec M, Roth A, Hug H, Kersten S, Albrecht H, Schwede T, Meyer UA, Rucker C: Sulfonylureas and glinides exhibit peroxisome proliferator-activated receptor gamma activity: a combined virtual screening and biological assay approach. Mol Pharmacol. 2007 Feb;71(2):398-406. Epub 2006 Nov 2. [PubMed:17082235]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. Bidstrup TB, Bjornsdottir I, Sidelmann UG, Thomsen MS, Hansen KT: CYP2C8 and CYP3A4 are the principal enzymes involved in the human in vitro biotransformation of the insulin secretagogue repaglinide. Br J Clin Pharmacol. 2003 Sep;56(3):305-14. [PubMed:12919179]
  4. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. Bidstrup TB, Bjornsdottir I, Sidelmann UG, Thomsen MS, Hansen KT: CYP2C8 and CYP3A4 are the principal enzymes involved in the human in vitro biotransformation of the insulin secretagogue repaglinide. Br J Clin Pharmacol. 2003 Sep;56(3):305-14. [PubMed:12919179]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. He J, Qiu Z, Li N, Yu Y, Lu Y, Han D, Li T, Zhao D, Sun W, Fang F, Zheng J, Fan H, Chen X: Effects of SLCO1B1 polymorphisms on the pharmacokinetics and pharmacodynamics of repaglinide in healthy Chinese volunteers. Eur J Clin Pharmacol. 2011 Jul;67(7):701-7. doi: 10.1007/s00228-011-0994-7. Epub 2011 Feb 17. [PubMed:21327909]

Drug created on June 13, 2005 07:24 / Updated on January 19, 2018 10:52