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药品详细

Insulin Glargine (甘精胰岛素 )

化学结构式图
没有图片
中文名
甘精胰岛素
英文名
Insulin Glargine
分子式
Not Available
化学名
分子量
CAS号
160337-95-1
ATC分类
A10A 未知
药物类型
biotech
阶段
商品名
Lantus (Sanofi-Aventis);Lantus SoloStar;
同义名
Insulin Glargine (rDNA origin);
基本介绍

Insulin glargine is produced by recombinant DNA technology using a non-pathogenic laboratory strain of Escherichia coli (K12) as the production organism. It is an analogue of human insulin made by replacing the asparagine residue at position A21 of the A-chain with glycine and adding two arginines to the C-terminus (positions B31 and 32) of the B-chain. The resulting protein is soluble at pH 4 and forms microprecipitates at physiological pH 7.4. Small amounts of insulin glargine are slowly released from microprecipitates giving the drug a long duration of action and no pronounced peak concentration.

生产厂家
  • Sanofi aventis us llc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Chatterjee S, Tringham JR, Davies MJ: Insulin glargine and its place in the treatment of Types 1 and 2 diabetes mellitus. Expert Opin Pharmacother. 2006 Jul;7(10):1357-71. Pubmed
  2. Dunn CJ, Plosker GL, Keating GM, McKeage K, Scott LJ: Insulin glargine: an updated review of its use in the management of diabetes mellitus. Drugs. 2003;63(16):1743-78. Pubmed
  3. Home PD, Ashwell SG: An overview of insulin glargine. Diabetes Metab Res Rev. 2002 Sep-Oct;18 Suppl 3:S57-63. Pubmed
  4. Jones R: Insulin glargine (Aventis Pharma). IDrugs. 2000 Sep;3(9):1081-7. Pubmed
  5. Wang F, Carabino JM, Vergara CM: Insulin glargine: a systematic review of a long-acting insulin analogue. Clin Ther. 2003 Jun;25(6):1541-77, discussion 1539-40. Pubmed
  6. Warren E, Weatherley-Jones E, Chilcott J, Beverley C: Systematic review and economic evaluation of a long-acting insulin analogue, insulin glargine. Health Technol Assess. 2004 Nov;8(45):iii, 1-57. Pubmed
剂型
Form Route Strength
Injection, solution Subcutaneous 100 units/ml
规格
Unit description Cost Unit
Lantus SoloStar 100 unit/ml Solution 1 Box = Five 3ml Syringes 223.89 USD box
Lantus 100 unit/ml Solution 10ml Vial 111.88 USD vial
Lantus for OptiClik 100 unit/ml Solution 3ml Cartridge 44.78 USD cartridge
Lantus 100 unit/ml cartridge 14.35 USD ml
Lantus solostar 100 unit/ml 14.35 USD ml
化合物类型
Type biotech
Classes Not Available
Substructures Not Available
适应症
Diabetes 糖尿病;
药理
Indication For the treatment of Type 1 or 2 diabetes mellitus in patients over 17 years old who require a long-acting (basal) insulin for the control of hyperglycemia. May be used in pediatric patients with Type 1 diabetes mellitus who require a long-acting (basal) insulin for glycemic control.
Pharmacodynamics Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, a basal level of insulin is supplemented with insulin spikes following meals. Increased insulin secretion following meals is responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin glargine is a long-acting insulin analogue with a flat and predictable action profile. It is used to mimic the basal levels of insulin in diabetic individuals. The onset of action of insulin glargine is approximately 90 minutes and its duration of action is up to 24 hours.
Mechanism of action Insulin glargine binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism. Insulin glargine is completely soluble at pH 4, the pH of administered solution, and has low solubility at physiological pH 7.4. Upon subcuteous injection, the solution is neutralized resulting in the formation of microprecipitates. Small amounts of insulin glargine are released from microprecipitates giving the drug a relatively constant concentration over time profile over 24 hours with no pronounced peak. This release mechanism allows the drug to mimic basal insulin levels within the body.
Absorption Forms microprecipitates following subcutaneous injection. Slow release of insulin glargine from microprecipitates provides a relatively constant concentration of insulin over 24 hours. Onset of action is approximately 1.1 hours.
Volume of distribution Not Available
Protein binding Not Available
Metabolism

Partly metabolized to two active metabolites with similar in vitro activity to insulin: A21-Gly-insulin and A21-Gly-des-B30-Thr-insulin.

Route of elimination Not Available
Half life Not reported in humans; 30 hours in vitro in mammalian reticulocytes.
Clearance Not Available
Toxicity Inappropriately high dosages relative to food intake and/or energy expenditure may result in severe and sometimes prolonged and life-threatening hypoglycemia. Neurogenic (autonomic) signs and symptoms of hypoglycemia include trembling, palpitations, sweating, anxiety, hunger, nausea and tingling. Neuroglycopenic signs and symptoms of hypoglycemia include difficulty concentrating, lethargy/weakness, confusion, drowsiness, vision changes, difficulty speaking, headache, and dizziness. Mild hypoglycemia is characterized by the presence of autonomic symptoms. Moderate hypoglycemia is characterized by the presence of autonomic and neuroglycopenic symptoms. Individuals may become unconscious in severe cases of hypoglycemia. Other adverse events that may occur include allergic reaction, injection site reaction, lipodystrophy, pruritis, and rash.
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State liquid
Melting point 81 oC (Khachidze, D.G. et al., J. Biol. Phys. Chem. 1:64-67 (2001))
Experimental Properties
Property Value Source
hydrophobicity 0.098 PhysProp
isoelectric point 6.88 Various sources
药物相互作用
Drug Interaction
Acebutolol The beta-blocker, acebutolol, may decrease symptoms of 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.
Esmolol The beta-blocker, esmolol, may decrease symptoms of hypoglycemia.
Labetalol The beta-blocker, labetolol, 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.
Propranolol The beta-blocker, propranolol, may decrease symptoms of hypoglycemia.
Somatropin recombinant Somatropin may antagonize the hypoglycemic effect of insulin glargine. 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.
食物相互作用
Not Available

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