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Repaglinide

产品号 DB00912 公司名称 DrugBank
CAS号 135062-02-1 公司网站 http://www.ualberta.ca/
分子式 C27H36N2O4 电 话 (780) 492-3111
分子量 452.58574 传 真
纯 度 电子邮件 david.wishart@ualberta.ca
保 存 Chembase数据库ID: 788

产品价格信息

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产品别名

标题
Repaglinide
IUPAC标准名
2-ethoxy-4-({[(1S)-3-methyl-1-[2-(piperidin-1-yl)phenyl]butyl]carbamoyl}methyl)benzoic acid
IUPAC传统名
repaglinide
商标名
GlucoNorm
Prandin
别名
Repaglinida [INN-Spanish]
repaglinide
AG-EE 623 ZW
Repaglinidum [INN-Latin]
AG-EE 388 ZW

产品登记号

PubChem SID 46508150
PubChem CID 65981
CAS号 135062-02-1

产品性质

疏水性(logP) 5.9

产品详细信息

详细说明 (English)
Item Information
Drug 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 na?ve 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.
Indication For the treatment of non-insulin dependent-diabetes mellitus in conjunction with diet and exercise.
Pharmacology 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.
Toxicity LD50 >1 g/kg (rat) (W. Grell)
Affected Organisms
Humans and other mammals
Biotransformation 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.
Absorption Rapidly and completely absorbed following oral administration. Peak plasma concentrations are observed within 1 hour (range 0.5-1.4 hours). Absolutely bioavailability is approximately 56%. Maximal biological effect is observed within 3-3.5 hours and plasma insulin levels remain elevated for 4-6 hours
Half Life 1 hour
Protein Binding >98% (e.g. to to albumin and α1-acid glycoprotein)
Elimination 90% eliminated in feces (<2% as unchanged drug), 8% in urine (0.1% as unchanged drug)
Distribution 31 L following IV administration in healthy individuals
Clearance 33-38 L/hour following IV administration
External Links
Wikipedia
RxList
PDRhealth
Drugs.com

参考文献