Tìm theo
Glyburide
Các tên gọi khác (10 ) :
  • 1-((P-(2-(5-chloro-O-Anisamido)ethyl)phenyl)sulfonyl)-3-cyclohexylurea
  • 1-(P-(2-(5-chloro-2-Methoxybenzamido)ethyl)benzenesulfonyl)-3-cyclohexylurea
  • 5-chloro-N-(2-(4-((((Cyclohexylamino)carbonyl)amino)sulfonyl)phenyl)ethyl)-2-methoxybenzamide
  • Diabeta
  • Glibenclamida
  • Glibenclamide
  • Glibenclamidum
  • Glyburide
  • Glynase
  • Micronase
Hormon, Nội tiết tố
Thuốc Gốc
Small Molecule
CAS: 10238-21-8
ATC: A10BB01
ĐG : Advanced Pharmaceutical Services Inc.
CTHH: C23H28ClN3O5S
PTK: 494.004
Glyburide is an oral antihyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus (NIDDM). It belongs to the sulfonylurea class of insulin secretagogues, which act by stimulating β cells of the pancreas to release insulin. Sulfonylureas increase both basal insulin secretion and meal-stimulated insulin release. Medications in this class differ in their dose, rate of absorption, duration of action, route of elimination and binding site on their target pancreatic β cell receptor. Sulfonylureas also increase peripheral glucose utilization, decrease hepatic gluconeogenesis and may increase the number and sensitivity of insulin receptors. Sulfonylureas are associated with weight gain, though less so than insulin. Due to their mechanism of action, sulfonylureas may cause hypoglycemia and require consistent food intake to decrease this risk. The risk of hypoglycemia is increased in elderly, debilitated and malnourished individuals. Glyburide has been shown to decrease fasting plasma glucose, postprandial blood glucose and glycosolated hemoglobin (HbA1c) levels (reflective of the last 8-10 weeks of glucose control). Glyburide appears to be completely metabolized, likely in the liver. Although its metabolites exert a small hypoglycemic effect, their contribution to glyburide's hypoglycemic effect is thought to be clinically unimportant. Glyburide metabolites are excreted in urine and feces in approximately equal proportions. The half-life of glyburide appears to be unaffected in those with a creatinine clearance of greater than 29 ml/min/1.73m2.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C23H28ClN3O5S
Phân tử khối
494.004
Monoisotopic mass
493.143819418
InChI
InChI=1S/C23H28ClN3O5S/c1-32-21-12-9-17(24)15-20(21)22(28)25-14-13-16-7-10-19(11-8-16)33(30,31)27-23(29)26-18-5-3-2-4-6-18/h7-12,15,18H,2-6,13-14H2,1H3,(H,25,28)(H2,26,27,29)
InChI Key
InChIKey=ZNNLBTZKUZBEKO-UHFFFAOYSA-N
IUPAC Name
5-chloro-N-[2-(4-{[(cyclohexylcarbamoyl)amino]sulfonyl}phenyl)ethyl]-2-methoxybenzamide
Traditional IUPAC Name
5-chloro-N-(2-{4-[(cyclohexylcarbamoyl)aminosulfonyl]phenyl}ethyl)-2-methoxybenzamide
SMILES
COC1=C(C=C(Cl)C=C1)C(=O)NCCC1=CC=C(C=C1)S(=O)(=O)NC(=O)NC1CCCCC1
Độ tan chảy
169 °C
Độ hòa tan
4 mg/L (at 27 °C)
logP
4.7
logS
-5.09
pKa (strongest acidic)
4.32
pKa (Strongest Basic)
-1.2
PSA
113.6 Å2
Refractivity
126.98 m3·mol-1
Polarizability
51.75 Å3
Rotatable Bond Count
7
H Bond Acceptor Count
5
H Bond Donor Count
3
Physiological Charge
-1
Number of Rings
3
Bioavailability
1
Rule of Five
true
MDDR-Like Rule
true
Dược Lực Học : Glyburide, a second-generation sulfonylurea antidiabetic agent, lowers blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. With chronic administration in Type II diabetic patients, the blood glucose lowering effect persists despite a gradual decline in the insulin secretory response to the drug. Extrapancreatic effects may be involved in the mechanism of action of oral sulfonyl-urea hypoglycemic drugs. The combination of glibenclamide and metformin may have a synergistic effect, since both agents act to improve glucose tolerance by different but complementary mechanisms. In addition to its blood glucose lowering actions, glyburide produces a mild diuresis by enhancement of renal free water clearance. Glyburide is twice as potent as the related second-generation agent glipizide.
Cơ Chế Tác Dụng : Glyburide is an oral antihyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus (NIDDM). It belongs to the sulfonylurea class of insulin secretagogues, which act by stimulating β cells of the pancreas to release insulin. Sulfonylureas increase both basal insulin secretion and meal-stimulated insulin release. Medications in this class differ in their dose, rate of absorption, duration of action, route of elimination and binding site on their target pancreatic β cell receptor. Sulfonylureas also increase peripheral glucose utilization, decrease hepatic gluconeogenesis and may increase the number and sensitivity of insulin receptors. Sulfonylureas are associated with weight gain, though less so than insulin. Due to their mechanism of action, sulfonylureas may cause hypoglycemia and require consistent food intake to decrease this risk. The risk of hypoglycemia is increased in elderly, debilitated and malnourished individuals. Glyburide has been shown to decrease fasting plasma glucose, postprandial blood glucose and glycosolated hemoglobin (HbA1c) levels (reflective of the last 8-10 weeks of glucose control). Glyburide appears to be completely metabolized, likely in the liver. Although its metabolites exert a small hypoglycemic effect, their contribution to glyburide's hypoglycemic effect is thought to be clinically unimportant. Glyburide metabolites are excreted in urine and feces in approximately equal proportions. The half-life of glyburide appears to be unaffected in those with a creatinine clearance of greater than 29 ml/min/1.73m2. Sulfonylureas such as glyburide bind to ATP-sensitive potassium channels on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Depolarization stimulates calcium ion influx through voltage-sensitive calcium channels, raising intracellular concentrations of calcium ions, which induces the secretion, or exocytosis, of insulin.
Dược Động Học :
▧ Absorption :
Significant absorption within 1 hour and peak plasma levels are reached in 2 to 4 hours. Onset of action occurs within one hour.
▧ Volume of Distribution :
Steady state Vd=0.125 L/kg; Vd during elimination phase=0.155 L/kg.
▧ Protein binding :
Unchanged drug is ~99% bound to serum proteins; 4-trans-hydroxyglyburide is greater than 97% bound to serum proteins. Protein binding is primarily nonionic making glyburide and is less likely to displace or be displaced by drugs that bind via an ionic mechanism.
▧ Metabolism :
Primarily hepatic (mainly cytochrome P450 3A4). The major metabolite is the 4-trans-hydroxy derivative. A second metabolite, the 3-cis-hydroxy derivative, also occurs. These metabolites do not contribute clinically significant hypoglycemic action in humans as they are only weakly active; however, retention of 4-trans-hydroxyglyburide may prolong the hypoglycemic effect of the agent in those with severe renal impairment.
▧ Route of Elimination :
Glyburide is excreted as metabolites in the bile and urine, approximately 50% by each route. This dual excretory pathway is qualitatively different from that of other sulfonylureas, which are excreted primarily in the urine.
▧ Half Life :
1.4-1.8 hours (unchanged drug only); 10 hours (metabolites included). Duration of effect is 12-24 hours.
▧ Clearance :
78 ml/hr/kg in healthy adults. Clearance may be substantially decreased in those with severe renal impairment.
Độc Tính : Oral rat LD50: > 20,000 mg/kg. Oral mouse LD50: 3250 mg/kg.
Chỉ Định : Indicated as an adjunct to diet to lower the blood glucose in patients with NIDDM whose hyperglycemia cannot be satisfactorily controlled by diet alone.
Tương Tác Thuốc :
  • Acebutolol Acebutolol may decrease symptoms of hypoglycemia and increase the time required for the body to compensate for hypoglycemia.
  • Acetylsalicylic acid Acetylsalicylic acid increases the effect of the sulfonylurea, glibenclamide.
  • 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.
  • Bismuth Subsalicylate The salicylate, bismuth subsalicylate, increases the effect of the sulfonylurea, glibenclamide.
  • Bisoprolol The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.
  • Bosentan Increased risk of hepatic toxicity
  • Carteolol The beta-blocker, carteolol, may decrease symptoms of hypoglycemia.
  • Carvedilol The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
  • Chloramphenicol Chloramphenicol may increase the effect of sulfonylurea, glibenclamide.
  • Clofibrate Clofibrate may increase the effect of sulfonylurea, glibenclamide.
  • Colesevelam Colesevelam may decrease the serum concentration of Glyburide. Glyburide should be administered at least 4 hours before colesevelam to minimize the risk of an interaction.
  • Cyclosporine The sulfonylurea, glibenclamide, may increase the effect of cyclosporine.
  • Diazoxide Antagonism.
  • Dicoumarol Dicumarol may increase the effect of sulfonylurea, glibenclamide.
  • Esmolol The beta-blocker, esmolol, may decrease symptoms of hypoglycemia.
  • Glucosamine Possible hyperglycemia
  • Labetalol The beta-blocker, labetalol, may decrease symptoms of hypoglycemia.
  • Magnesium salicylate The salicylate, magnesium salicylate, increases the effect of the sulfonylurea, glibenclamide.
  • 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.
  • Phenylbutazone Phenylbutazone increases the effect of the hypoglycemic agent
  • Pindolol The beta-blocker, pindolol, may decrease symptoms of hypoglycemia.
  • Practolol The beta-blocker, practolol, may decrease symptoms of hypoglycemia.
  • Propranolol The beta-blocker, propranolol, may decrease symptoms of hypoglycemia.
  • Rifampicin Rifampin may decrease the effect of sulfonylurea, glibenclamide.
  • Salicylate-sodium The salicylate, salicylate-sodium, increases the effect of the sulfonylurea, glibenclamide.
  • Salsalate The salicylate, salsalate, increases the effect of the sulfonylurea, glibenclamide.
  • Somatropin recombinant Somatropin may antagonize the hypoglycemic effect of glibenclamide. Monitor for changes in fasting and postprandial blood sugars.
  • Sotalol The beta-blocker, sotalol, may decrease symptoms of hypoglycemia.
  • Timolol The beta-blocker, timolol, may decrease symptoms of hypoglycemia.
  • Trisalicylate-choline The salicylate, trisalicylate-choline, increases the effect of the sulfonylurea, glibenclamide.
Liều Lượng & Cách Dùng : Tablet - Oral - 2.5 mg
Tablet - Oral - 5 mg
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Daonil
  • Công ty :
    Sản phẩm biệt dược : Delmide
  • Công ty : Sanofi-Aventis
    Sản phẩm biệt dược : Diabeta
  • Công ty :
    Sản phẩm biệt dược : Euglucon
  • Công ty :
    Sản phẩm biệt dược : Glynase
  • Công ty :
    Sản phẩm biệt dược : Micronase
  • Công ty : Novopharm
    Sản phẩm biệt dược : Novo-Glyburide
  • Công ty :
    Sản phẩm biệt dược : Semi-Daonil
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01016
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=3488
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46509154
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07022
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00336
ChemSpider
http://www.chemspider.com/Chemical-Structure.3368.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0378-1113-01
PharmGKB
http://www.pharmgkb.org/drug/PA449782
Wikipedia
http://en.wikipedia.org/wiki/Glibenclamide
RxList
http://www.rxlist.com/cgi/generic/glybur.htm
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