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Identification
NameRepaglinide
Accession NumberDB00912  (APRD00439)
TypeSmall Molecule
GroupsApproved, 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
Prandin
Repaglinida
Repaglinidum
Surepost
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act Repaglinidetablet2 mgoralActavis Pharma Company2010-10-18Not applicableCanada
Act Repaglinidetablet1 mgoralActavis Pharma Company2010-10-18Not applicableCanada
Act Repaglinidetablet0.5 mgoralActavis Pharma Company2010-10-18Not 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
Gluconorm 0.5mgtablet0.5 mgoralNovo Nordisk Canada Inc1999-06-21Not applicableCanada
Gluconorm 1.0mgtablet1.0 mgoralNovo Nordisk Canada Inc1999-06-21Not applicableCanada
Gluconorm 2.0mgtablet2.0 mgoralNovo Nordisk Canada Inc1999-06-21Not applicableCanada
Mylan-repaglinidetablet0.5 mgoralMylan Pharmaceuticals UlcNot applicableNot applicableCanada
Mylan-repaglinidetablet2 mgoralMylan Pharmaceuticals UlcNot applicableNot applicableCanada
Mylan-repaglinidetablet1 mgoralMylan Pharmaceuticals UlcNot applicableNot applicableCanada
PMS-repaglinidetablet0.5 mgoralPharmascience Inc2010-10-20Not applicableCanada
PMS-repaglinidetablet1.0 mgoralPharmascience Inc2010-10-20Not applicableCanada
PMS-repaglinidetablet2.0 mgoralPharmascience Inc2010-10-20Not applicableCanada
Prandintablet.5 mg/1oralCarilion Materials Management2000-01-03Not applicableUs
Prandintablet.5 mg/1oralNovo Nordisk2000-01-03Not applicableUs
Prandintablet1 mg/1oralCardinal Health2000-01-03Not applicableUs
Prandintablet1 mg/1oralPhysicians Total Care, Inc.2000-01-03Not applicableUs
Prandintablet2 mg/1oralPhysicians Total Care, Inc.2000-01-03Not applicableUs
Prandintablet2 mg/1oralREMEDYREPACK INC.2011-10-04Not applicableUs
Prandintablet.5 mg/1oralLake Erie Medical DBA Quality Care Products LLC2010-10-12Not applicableUs
Prandintablet2 mg/1oralNovo Nordisk2000-01-03Not applicableUs
Prandintablet1 mg/1oralCarilion Materials Management2000-01-03Not applicableUs
Prandintablet1 mg/1oralNovo Nordisk2000-01-03Not applicableUs
Repaglinidetablet2.0 mgoralPro Doc Limitee2013-11-28Not applicableCanada
Repaglinidetablet1.0 mgoralPro Doc Limitee2013-11-28Not applicableCanada
Repaglinidetablet0.5 mgoralPro Doc Limitee2013-11-28Not applicableCanada
Sandoz Repaglinidetablet2 mgoralSandoz Canada Incorporated2011-02-17Not applicableCanada
Sandoz Repaglinidetablet1 mgoralSandoz Canada Incorporated2011-02-17Not applicableCanada
Sandoz Repaglinidetablet0.5 mgoralSandoz Canada Incorporated2011-02-17Not applicableCanada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-repaglinidetablet2.0 mgoralApotex Inc2012-10-16Not applicableCanada
Apo-repaglinidetablet1.0 mgoralApotex Inc2012-10-16Not applicableCanada
Apo-repaglinidetablet0.5 mgoralApotex Inc2012-10-16Not applicableCanada
Repaglinidetablet2 mg/1oralBreckenridge Pharmaceutical, Inc.2015-05-01Not applicableUs
Repaglinidetablet2 mg/1oralSandoz Inc2014-01-22Not applicableUs
Repaglinidetablet.5 mg/1oralMylan Pharmaceuticals Inc.2013-08-27Not applicableUs
Repaglinidetablet1 mg/1oralAmerican Health Packaging2015-03-30Not applicableUs
Repaglinidetablet.5 mg/1oralCitron Pharma LLC2014-01-22Not applicableUs
Repaglinidetablet1 mg/1oralBreckenridge Pharmaceutical, Inc.2015-05-01Not applicableUs
Repaglinidetablet1 mg/1oralSandoz Inc2014-01-22Not applicableUs
Repaglinidetablet2 mg/1oralGolden State Medical Supply, Inc.2015-12-17Not applicableUs
Repaglinidetablet2 mg/1oralAurobindo Pharma Limited2014-01-22Not applicableUs
Repaglinidetablet.5 mg/1oralBreckenridge Pharmaceutical, Inc.2015-05-01Not applicableUs
Repaglinidetablet.5 mg/1oralSandoz Inc2013-12-27Not applicableUs
Repaglinidetablet1 mg/1oralGolden State Medical Supply, Inc.2015-12-17Not applicableUs
Repaglinidetablet1 mg/1oralAurobindo Pharma Limited2014-01-22Not applicableUs
Repaglinidetablet2 mg/1oralMylan Institutional Inc.2014-02-24Not applicableUs
Repaglinidetablet2 mg/1oralPaddock Laboratories, LLC2014-01-22Not applicableUs
Repaglinidetablet.5 mg/1oralGolden State Medical Supply, Inc.2015-12-07Not applicableUs
Repaglinidetablet.5 mg/1oralAurobindo Pharma Limited2014-01-22Not applicableUs
Repaglinidetablet1 mg/1oralMylan Institutional Inc.2014-02-27Not applicableUs
Repaglinidetablet1 mg/1oralPaddock Laboratories, LLC2014-01-22Not applicableUs
Repaglinidetablet2 mg/1oralSun Pharmaceutical Industries, Inc.2013-07-11Not applicableUs
Repaglinidetablet1 mg/1oralSun Pharmaceutical Industries, Inc.2013-07-11Not applicableUs
Repaglinidetablet.5 mg/1oralMylan Institutional Inc.2013-11-21Not applicableUs
Repaglinidetablet.5 mg/1oralPaddock Laboratories, LLC2013-08-09Not applicableUs
Repaglinidetablet2 mg/1oralCitron Pharma LLC2014-01-22Not applicableUs
Repaglinidetablet2 mg/1oralAv Kare, Inc.2013-12-12Not applicableUs
Repaglinidetablet2 mg/1oralMylan Pharmaceuticals Inc.2014-01-22Not applicableUs
Repaglinidetablet2 mg/1oralAmerican Health Packaging2015-03-30Not applicableUs
Repaglinidetablet1 mg/1oralCitron Pharma LLC2014-01-22Not applicableUs
Repaglinidetablet1 mg/1oralAv Kare, Inc.2013-12-12Not applicableUs
Repaglinidetablet1 mg/1oralMylan Pharmaceuticals Inc.2014-01-22Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
GlucoNormNovo Nordisk
Brand mixtures
NameLabellerIngredients
PrandimetNovo Nordisk
Repaglinide and Metformin HydrochlorideLupin Pharmaceuticals, Inc.
SaltsNot Available
Categories
UNII668Z8C33LU
CAS number135062-02-1
WeightAverage: 452.5857
Monoisotopic: 452.26750765
Chemical FormulaC27H36N2O4
InChI KeyInChIKey=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[C@@H](CC(C)C)C2=CC=CC=C2N2CCCCC2)=C1)C(O)=O
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPiperidines
Sub ClassPhenylpiperidines
Direct ParentPhenylpiperidines
Alternative Parents
Substituents
  • Phenylpiperidine
  • Phenylacetamide
  • Phenylpropylamine
  • Benzoic acid
  • Benzoic acid or derivatives
  • Substituted aniline
  • Dialkylarylamine
  • Phenol ether
  • Benzoyl
  • Aniline
  • Alkyl aryl ether
  • Benzenoid
  • Monocyclic benzene moiety
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Azacycle
  • Monocarboxylic acid or derivatives
  • Ether
  • Carboxylic acid
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationAs an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
PharmacodynamicsInsulin 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 actionRepaglinide 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.
Related Articles
AbsorptionRapidly 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.

SubstrateEnzymesProduct
Repaglinide
hydroxyrepaglinideDetails
Repaglinide
repaglinide aromatic amineDetails
Route of elimination90% eliminated in feces (<2% as unchanged drug), 8% in urine (0.1% as unchanged drug)
Half life1 hour
Clearance

33-38 L/hour following IV administration

ToxicityLD50 >1 g/kg (rat) (W. Grell)
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Repaglinide Action PathwayDrug actionSMP00454
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
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/1
Tabletoral2 mg/1
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
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2111851 No2002-02-262011-06-21Canada
US6677358 No1998-06-122018-06-12Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point130-131 °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 FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
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
ATC CodesA10BD14A10BX02
AHFS Codes
  • 68:20.16
PDB EntriesNot Available
FDA labelDownload (175 KB)
MSDSDownload (57.3 KB)
Interactions
Drug Interactions
Drug
AbirateroneThe serum concentration of Repaglinide can be increased when it is combined with Abiraterone.
AcetohexamideAcetohexamide may increase the hypoglycemic activities of Repaglinide.
Acetylsalicylic acidAcetylsalicylic acid may increase the hypoglycemic activities of Repaglinide.
AlogliptinAlogliptin may increase the hypoglycemic activities of Repaglinide.
AripiprazoleThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Aripiprazole.
Arsenic trioxideThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Arsenic trioxide.
ArticaineThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Articaine.
AsenapineThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Asenapine.
AtazanavirThe serum concentration of Repaglinide can be increased when it is combined with Atazanavir.
BendroflumethiazideThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Bendroflumethiazide.
BetamethasoneThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Betamethasone.
BexaroteneThe serum concentration of Repaglinide can be decreased when it is combined with Bexarotene.
BoceprevirThe serum concentration of Repaglinide can be increased when it is combined with Boceprevir.
BosentanThe serum concentration of Repaglinide can be decreased when it is combined with Bosentan.
BrexpiprazoleThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Brexpiprazole.
BumetanideThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Bumetanide.
BuserelinThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Buserelin.
CanagliflozinCanagliflozin may increase the hypoglycemic activities of Repaglinide.
CeritinibThe serum concentration of Repaglinide can be increased when it is combined with Ceritinib.
ChlorothiazideThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Chlorothiazide.
ChlorpropamideRepaglinide may increase the hypoglycemic activities of Chlorpropamide.
ChlorthalidoneThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Chlorthalidone.
ClarithromycinThe serum concentration of Repaglinide can be increased when it is combined with Clarithromycin.
ClopidogrelThe serum concentration of Repaglinide can be increased when it is combined with Clopidogrel.
ClozapineThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Clozapine.
CobicistatThe serum concentration of Repaglinide can be increased when it is combined with Cobicistat.
CorticotropinThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Corticotropin.
Cortisone acetateThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Cortisone acetate.
CyclosporineThe serum concentration of Repaglinide can be increased when it is combined with Cyclosporine.
Cyproterone acetateThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Cyproterone acetate.
DabrafenibThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Dabrafenib.
DanazolThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Danazol.
DarunavirThe serum concentration of Repaglinide can be increased when it is combined with Darunavir.
DeferasiroxThe serum concentration of Repaglinide can be increased when it is combined with Deferasirox.
DesogestrelThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Desogestrel.
DexamethasoneThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Dexamethasone.
DiazoxideThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Diazoxide.
DienogestThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Dienogest.
DihydrotestosteroneDihydrotestosterone may increase the hypoglycemic activities of Repaglinide.
DisopyramideRepaglinide may increase the hypoglycemic activities of Disopyramide.
DrospirenoneThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Drospirenone.
EltrombopagThe serum concentration of Repaglinide can be increased when it is combined with Eltrombopag.
EpinephrineThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Epinephrine.
ErythromycinThe serum concentration of Repaglinide can be increased when it is combined with Erythromycin.
EstradiolThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Estradiol.
Estrone sulfateThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Estropipate.
Etacrynic acidThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Ethacrynic acid.
Ethinyl EstradiolThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Ethinyl Estradiol.
Ethynodiol diacetateThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Ethynodiol.
EtonogestrelThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Etonogestrel.
EverolimusThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Everolimus.
FludrocortisoneThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Fludrocortisone.
FosamprenavirThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Fosamprenavir.
FurosemideThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Furosemide.
GemfibrozilThe serum concentration of Repaglinide can be increased when it is combined with Gemfibrozil.
GliclazideGliclazide may increase the hypoglycemic activities of Repaglinide.
GlimepirideRepaglinide may increase the hypoglycemic activities of Glimepiride.
GlipizideRepaglinide may increase the hypoglycemic activities of Glipizide.
GliquidoneGliquidone may increase the hypoglycemic activities of Repaglinide.
GlyburideGlyburide may increase the hypoglycemic activities of Repaglinide.
GoserelinThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Goserelin.
HistrelinThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Histrelin.
HydrochlorothiazideThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Hydrochlorothiazide.
HydrocortisoneThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Hydrocortisone.
Hydroxyprogesterone caproateThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Hydroxyprogesterone caproate.
IdelalisibThe serum concentration of Repaglinide can be increased when it is combined with Idelalisib.
IloperidoneThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Iloperidone.
IndapamideThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Indapamide.
IndinavirThe serum concentration of Repaglinide can be increased when it is combined with Indinavir.
Insulin AspartInsulin Aspart may increase the hypoglycemic activities of Repaglinide.
Insulin DegludecRepaglinide may increase the hypoglycemic activities of Insulin degludec.
Insulin DetemirInsulin Detemir may increase the hypoglycemic activities of Repaglinide.
Insulin GlargineRepaglinide may increase the hypoglycemic activities of Insulin Glargine.
Insulin GlulisineInsulin Glulisine may increase the hypoglycemic activities of Repaglinide.
Insulin HumanRepaglinide may increase the hypoglycemic activities of Insulin Regular.
Insulin LisproRepaglinide may increase the hypoglycemic activities of Insulin Lispro.
ItraconazoleThe serum concentration of Repaglinide can be increased when it is combined with Itraconazole.
KetoconazoleThe serum concentration of Repaglinide can be increased when it is combined with Ketoconazole.
LanreotideRepaglinide may increase the hypoglycemic activities of Lanreotide.
LeuprolideThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Leuprolide.
LevonorgestrelThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Levonorgestrel.
LinagliptinLinagliptin may increase the hypoglycemic activities of Repaglinide.
Lipoic AcidLipoic Acid may increase the hypoglycemic activities of Repaglinide.
LopinavirThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Lopinavir.
LurasidoneThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Lurasidone.
MecaserminRepaglinide may increase the hypoglycemic activities of Mecasermin.
Medroxyprogesterone AcetateThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Medroxyprogesterone Acetate.
Megestrol acetateThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Megestrol acetate.
MestranolThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Mestranol.
MetforminMetformin may increase the hypoglycemic activities of Repaglinide.
MethotrimeprazineThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Methotrimeprazine.
MethyclothiazideThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Methyclothiazide.
MethylprednisoloneThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Methylprednisolone.
MetolazoneThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Metolazone.
MifepristoneThe serum concentration of Repaglinide can be increased when it is combined with Mifepristone.
MitotaneThe serum concentration of Repaglinide can be decreased when it is combined with Mitotane.
NadololThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Nadolol.
NateglinideRepaglinide may increase the hypoglycemic activities of Nateglinide.
NefazodoneThe serum concentration of Repaglinide can be increased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Repaglinide can be increased when it is combined with Nelfinavir.
NiacinThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Niacin.
NilotinibThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Nilotinib.
NorethisteroneThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Norethindrone.
NorgestimateThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Norgestimate.
OctreotideRepaglinide may increase the hypoglycemic activities of Octreotide.
OlanzapineThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Olanzapine.
OxandroloneOxandrolone may increase the hypoglycemic activities of Repaglinide.
PaliperidoneThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Paliperidone.
ParoxetineParoxetine may increase the hypoglycemic activities of Repaglinide.
PasireotideRepaglinide may increase the hypoglycemic activities of Pasireotide.
PegvisomantPegvisomant may increase the hypoglycemic activities of Repaglinide.
PentamidineRepaglinide may increase the hypoglycemic activities of Pentamidine.
PhenelzinePhenelzine may increase the hypoglycemic activities of Repaglinide.
PhenytoinThe metabolism of Repaglinide can be increased when combined with Phenytoin.
PipotiazineThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Pipotiazine.
PosaconazoleThe serum concentration of Repaglinide can be increased when it is combined with Posaconazole.
PrednisoloneThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Prednisolone.
PrednisoneThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Prednisone.
ProgesteroneThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Progesterone.
QuetiapineThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Quetiapine.
QuinineRepaglinide may increase the hypoglycemic activities of Quinine.
Repository corticotropinThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Repository corticotropin.
RifampicinThe serum concentration of Repaglinide can be decreased when it is combined with Rifampicin.
RisperidoneThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Risperidone.
RitonavirThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Ritonavir.
RosiglitazoneThe metabolism of Repaglinide can be decreased when combined with Rosiglitazone.
SaquinavirThe serum concentration of Repaglinide can be increased when it is combined with Saquinavir.
SaxagliptinSaxagliptin may increase the hypoglycemic activities of Repaglinide.
SiltuximabThe serum concentration of Repaglinide can be decreased when it is combined with Siltuximab.
SirolimusThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Sirolimus.
SparfloxacinSparfloxacin may increase the hypoglycemic activities of Repaglinide.
St. John's WortThe serum concentration of Repaglinide can be decreased when it is combined with St. John&#39;s Wort.
SulfadiazineRepaglinide may increase the hypoglycemic activities of Sulfadiazine.
SulfamethoxazoleRepaglinide may increase the hypoglycemic activities of Sulfamethoxazole.
SulfisoxazoleRepaglinide may increase the hypoglycemic activities of Sulfisoxazole.
SunitinibRepaglinide may increase the hypoglycemic activities of Sunitinib.
TacrolimusThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Tacrolimus.
TelaprevirThe serum concentration of Repaglinide can be increased when it is combined with Telaprevir.
TelithromycinThe serum concentration of Repaglinide can be increased when it is combined with Telithromycin.
TemsirolimusThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Temsirolimus.
TeriflunomideThe serum concentration of Repaglinide can be increased when it is combined with Teriflunomide.
TestosteroneTestosterone may increase the hypoglycemic activities of Repaglinide.
TipranavirThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Tipranavir.
TocilizumabThe serum concentration of Repaglinide can be decreased when it is combined with Tocilizumab.
TolazamideRepaglinide may increase the hypoglycemic activities of Tolazamide.
TolbutamideTolbutamide may increase the hypoglycemic activities of Repaglinide.
TorasemideThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Torasemide.
TranylcypromineTranylcypromine may increase the hypoglycemic activities of Repaglinide.
TriamcinoloneThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Triamcinolone.
TrichlormethiazideThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Trichlormethiazide.
TrimethoprimThe metabolism of Repaglinide can be decreased when combined with Trimethoprim.
TriptorelinThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Triptorelin.
VildagliptinVildagliptin may increase the hypoglycemic activities of Repaglinide.
VoriconazoleThe serum concentration of Repaglinide can be increased when it is combined with Voriconazole.
VorinostatThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Vorinostat.
ZiprasidoneThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Ziprasidone.
Food Interactions
  • Take up to 30 minutes before meals.
  • When taken with a high-fat meal, AUC and Cmax decreases.

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
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) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation...
Gene Name:
PPARG
Uniprot ID:
P37231
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme...
Gene Name:
CYP2C8
Uniprot ID:
P10632
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
substrateinhibitor
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
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 colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.
Gene Name:
ALB
Uniprot ID:
P02768
Molecular Weight:
69365.94 Da
References
  1. Novo Nordisk. Prandin® (repaglinide) tablets prescribing information. Princeton, NJ; 2010 Mar 19.

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, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. Involved in the clearance of bile acids and organic anions from the liver.
Gene Name:
SLCO1B1
Uniprot ID:
Q9Y6L6
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 ]
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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12