Tìm theo
Repaglinide
Các tên gọi khác (6 ) :
  • AG-EE 388 ZW
  • AG-EE 623 ZW
  • Prandin
  • Repaglinida
  • Repaglinidum
  • Surepost
Insulin và nhóm Thuốc hạ đường huyết
Thuốc Gốc
Small Molecule
CAS: 135062-02-1
ATC: A10BX02
ĐG : Boehringer Ingelheim Ltd. , http://www.boehringer-ingelheim.com
CTHH: C27H36N2O4
PTK: 452.5857
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.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C27H36N2O4
Phân tử khối
452.5857
Monoisotopic mass
452.26750765
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
InChI Key
InChIKey=FAEKWTJYAYMJKF-QHCPKHFHSA-N
IUPAC Name
2-ethoxy-4-({[(1S)-3-methyl-1-[2-(piperidin-1-yl)phenyl]butyl]carbamoyl}methyl)benzoic acid
Traditional IUPAC Name
repaglinide
SMILES
CCOC1=C(C=CC(CC(=O)N[C@@H](CC(C)C)C2=CC=CC=C2N2CCCCC2)=C1)C(O)=O
Độ tan chảy
130-131 °C
Độ hòa tan
2.94e-03 g/l
logP
5.9
logS
-5.2
pKa (strongest acidic)
3.68
pKa (Strongest Basic)
4.82
PSA
78.87 Å2
Refractivity
131.83 m3·mol-1
Polarizability
51.49 Å3
Rotatable Bond Count
10
H Bond Acceptor Count
5
H Bond Donor Count
2
Physiological Charge
-1
Number of Rings
3
Bioavailability
1
Rule of Five
true
MDDR-Like Rule
true
Dược Lực Học : 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.
Cơ Chế Tác Dụng : 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. 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.
Dược Động Học :
▧ 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
Độc Tính : LD50 >1 g/kg (rat) (W. Grell)
Chỉ Định : As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Tương Tác Thuốc :
  • Acebutolol Acebutolol may decrease symptoms of hypoglycemia and increase the time required for the body to compensate for hypoglycemia.
  • Atenolol The beta-blocker, atenolol, may decrease symptoms of hypoglycemia.
  • Betaxolol The beta-blocker, betaxolol, may decrease symptoms of hypoglycemia.
  • Bevantolol The beta-blocker, bevantolol, may decrease symptoms of hypoglycemia.
  • Bisoprolol The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.
  • Carteolol The beta-blocker, carteolol, may decrease symptoms of hypoglycemia.
  • Carvedilol The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
  • Clarithromycin Clarithromycin may increase the effect of repaglinide.
  • Cyclosporine Cyclosporine may increase the therapeutic and adverse effects of repaglinide.
  • Erythromycin The macrolide, erythromycin, may increase the effect of repaglinide.
  • Esmolol The beta-blocker, esmolol, may decrease symptoms of hypoglycemia.
  • Fluvastatin Inhibitors of CYP3A4 and P-glycoprotein may increase serum concentrations of repaglinide. Monitor concomitant therapy closely.
  • Gemfibrozil Gemfibrozil may increase the effect and toxicity of repaglinide.
  • Glucosamine Possible hyperglycemia
  • Josamycin The macrolide, josamycin, may increase the effect of repaglinide.
  • Labetalol The beta-blocker, labetalol, may decrease symptoms of hypoglycemia.
  • Metoprolol The beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.
  • Nadolol The beta-blocker, nadolol, may decrease symptoms of hypoglycemia.
  • Oxprenolol The beta-blocker, oxprenolol, may decrease symptoms of hypoglycemia.
  • Penbutolol The beta-blocker, penbutolol, may decrease symptoms of hypoglycemia.
  • Pindolol The beta-blocker, pindolol, may decrease symptoms of hypoglycemia.
  • Practolol The beta-blocker, practolol, may decrease symptoms of hypoglycemia.
  • Pravastatin Substrates of organic anion transporters may increase levels of repaglinide. Monitor concomitant therapy closely.
  • Propranolol The beta-blocker, propranolol, may decrease symptoms of hypoglycemia.
  • Rifampicin Rifampin decreases the effect of repaglinide
  • Sotalol The beta-blocker, sotalol, may decrease symptoms of hypoglycemia.
  • Telithromycin Telithromycin may reduce clearance of Repaglinide. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Repaglinide if Telithromycin is initiated, discontinued or dose changed.
  • Timolol The beta-blocker, timolol, may decrease symptoms of hypoglycemia.
  • Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of repaglinide by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of repaglinide if voriconazole is initiated, discontinued or dose changed.
Liều Lượng & Cách Dùng : Tablet - Oral - 0.5 mg
Tablet - Oral - 1 mg
Tablet - Oral - 2 mg
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Prandin 2 mg tablet
    Giá bán buôn : USD >2.33
    Đơn vị tính : tablet
  • Biệt dược thương mại : Prandin 0.5 mg tablet
    Giá bán buôn : USD >2.47
    Đơn vị tính : tablet
  • Biệt dược thương mại : Prandin 1 mg tablet
    Giá bán buôn : USD >2.48
    Đơn vị tính : tablet
  • Biệt dược thương mại : Gluconorm 0.5 mg Tablet
    Giá bán buôn : USD >0.31
    Đơn vị tính : tablet
  • Biệt dược thương mại : Gluconorm 1 mg Tablet
    Giá bán buôn : USD >0.32
    Đơn vị tính : tablet
  • Biệt dược thương mại : Gluconorm 2 mg Tablet
    Giá bán buôn : USD >0.34
    Đơn vị tính : tablet
Nhà Sản Xuất
  • Công ty : Novo Nordisk
    Sản phẩm biệt dược : GlucoNorm
  • Công ty : Novo Nordisk
    Sản phẩm biệt dược : Prandin
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00912
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=65981
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46508150
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07670
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00594
ChemSpider
http://www.chemspider.com/Chemical-Structure.59377.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50153520
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/35356-303-01
PharmGKB
http://www.pharmgkb.org/drug/PA451234
Wikipedia
http://en.wikipedia.org/wiki/Repaglinide
RxList
http://www.rxlist.com/cgi/generic/prandin.htm
PDRhealth
http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/pra1343.shtml
Drugs.com
http://www.drugs.com/cdi/repaglinide.html
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