| Size | Price | Stock | Qty |
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| 100mg |
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| 250mg |
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| 500mg |
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| 1g |
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| 2g |
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Purity: ≥98%
Repaglinide (AG-EE388 ZW; AG-EE-623 ZW, Prandin, GlucoNorm, Surepost, NovoNorm) is a potent and short-acting potassium channel blocker with antidiabetic activity. It can lower blood glucose by stimulating the release of insulin from the pancreas. Repaglinide is an approved antidiabetic drug belonging to the meglitinide class of medications, and was invented in 1983. Repaglinide is an oral medication used for the treatment of type 2 diabetes mellitus. The mechanism of action of repaglinide involves promoting insulin release from β-islet cells of the pancreas.
| ln Vitro |
Repaglinide decreases postprandial glucose levels by boosting the early phase of insulin secretion and increasing the total quantity of insulin secreted[1].
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| ln Vivo |
Repaglinide (AG-EE 623ZW) has a t1/2 of less than an hour and is absorbed very quickly (tmax less than an hour). Repaglinide is also inactivated in the liver and eliminated through the bile in more than 90% of cases. Repaglinide (1 mg/kg po) in a rat model of type 2 diabetes (low-dose streptozotocin) is an effective (P<0.001) insulin-releasing drug.
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| Animal Protocol |
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| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
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. 90% eliminated in feces (<2% as unchanged drug), 8% in urine (0.1% as unchanged drug) 31 L following IV administration in healthy individuals 33-38 L/hour following IV administration Metabolism / Metabolites 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. Repaglinide has known human metabolites that include Repaglinide aromatic amine, 2-ethoxy-4-[2-[[1-[2-(4-hydroxybutylamino)phenyl]-3-methylbutyl]amino]-2-oxoethyl]benzoic acid, 3'-Hydroxy Repaglinide(Mixture of Diastereomers), 2-ethoxy-4-[2-[[3-hydroxy-3-methyl-1-(2-piperidin-1-ylphenyl)butyl]amino]-2-oxoethyl]benzoic acid, and 2-Hydroxy-4-[2-[[3-methyl-1-(2-piperidin-1-ylphenyl)butyl]amino]-2-oxoethyl]benzoic acid. Biological Half-Life 1 hour |
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| Toxicity/Toxicokinetics |
Hepatotoxicity
In several large clinical trials, serum aminotransferase elevations during repaglinide therapy were uncommon and similar in frequency with placebo. All serum enzyme elevations that occurred were asymptomatic and resolved rapidly with stopping therapy. Since its approval and with wide scale use, there have been a small number of reports of clinically apparent liver injury attributed to repaglinide. The time to onset ranged from 2 to 8 weeks and the pattern of serum enzyme elevations was typically cholestatic or mixed. Jaundice and pruritus were prominent. Immunoallergic features and autoantibodies were not present. All published cases have been self-limited, resolving within 1 to 2 months of stopping. Likelhood score: D (possible rare cause of clinically apparent liver injury). Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation No information is available on the use of repaglinide during breastfeeding. Repaglinide is a weak acid that is over 98% protein bound, so it is unlikely to pass into breastmilk in clinically important amounts. Monitor breastfed infants for signs of hypoglycemia such as jitteriness, excessive sleepiness, poor feeding, seizures cyanosis, apnea, or hypothermia. If there is concern, monitoring of the breastfed infant's blood glucose is advisable during maternal therapy with repaglinide. However, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding >98% (e.g. to to albumin and α1-acid glycoprotein) |
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| Additional Infomation |
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. |
| Molecular Formula |
C27H36N2O4
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| Molecular Weight |
452.59
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| Exact Mass |
452.267
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| CAS # |
135062-02-1
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| Related CAS # |
Repaglinide-d5;1217709-85-7
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| PubChem CID |
65981
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| Appearance |
White to off-white solid powder
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
672.9±55.0 °C at 760 mmHg
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| Melting Point |
129-130.2 °C
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| Flash Point |
360.8±31.5 °C
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| Vapour Pressure |
0.0±2.2 mmHg at 25°C
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| Index of Refraction |
1.568
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| LogP |
4.69
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
33
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| Complexity |
619
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CCOC1=C(C=CC(=C1)CC(=O)N[C@@H](CC(C)C)C2=CC=CC=C2N3CCCCC3)C(=O)O
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| InChi Key |
FAEKWTJYAYMJKF-QHCPKHFHSA-N
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| InChi Code |
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
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| Chemical Name |
2-ethoxy-4-[2-[[(1S)-3-methyl-1-(2-piperidin-1-ylphenyl)butyl]amino]-2-oxoethyl]benzoic acid
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.52 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.52 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.52 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2095 mL | 11.0475 mL | 22.0951 mL | |
| 5 mM | 0.4419 mL | 2.2095 mL | 4.4190 mL | |
| 10 mM | 0.2210 mL | 1.1048 mL | 2.2095 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
A Phase 3, 24-Week, Multi-Center, Open-Label, Randomized, Controlled Trial Comparing the Efficacy and Safety of Prandial Inhalation of Technosphere®/Insulin in Combination with Metformin or Technosphere®/Insulin Alone Versus 2 Oral Anti-Diabetic Agents (Metformin and a Secretagogue) in Subjects With Type 2 Diabetes Mellitus Sub-Optimally Controlled on Combination Metformin and a Secretagogue
CTID: null
Phase: Phase 3 Status: Completed
Date: 2006-12-01
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