Tìm theo
Insulin Lispro
Các tên gọi khác (1) :
  • Insulin Lispro Recombinant
Insulin và nhóm Thuốc hạ đường huyết
Thuốc Gốc
Biotech
CAS: 133107-64-9
ATC: A10AC04, A10AD04
ĐG : Eli Lilly & Co. , http://www.lilly.com
CTHH: C257H387N65O76S6
PTK: 5808.0000
Insulin lispro is a recombinant human insulin analogue produced in a specialized laboratory strain of Escherischia coli. Plasmid DNA transfected into the bacteria encodes for an analogue of human insulin that has a lysine at residuce B28 and proline at B29; these residues are reversed in endogenous human insulin. Reversal of these amino acid residues produces a rapid-acting insulin analogue. FDA approved on 1996.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C257H387N65O76S6
Phân tử khối
5808.0000
Độ tan chảy
81 °C
Độ kỵ nước
0.218
Điểm đẳng điện tích
5.39
Dược Lực Học : 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 lispro is a rapid-acting insulin analogue used to mimic postprandial insulin spikes in diabetic individuals. The onset of action of insulin lispro is 10-15 minutes. Its activity peaks 60 minutes following subcutaneous injection and its duration of action is 4-5 hours. Compared to regular human insulin, insulin lispro has a more rapid onset of action and a shorter duration of action. Insulin lispro is also shown to be equipotent to human insulin on a molar basis.
Cơ Chế Tác Dụng : Insulin lispro is a recombinant human insulin analogue produced in a specialized laboratory strain of Escherischia coli. Plasmid DNA transfected into the bacteria encodes for an analogue of human insulin that has a lysine at residuce B28 and proline at B29; these residues are reversed in endogenous human insulin. Reversal of these amino acid residues produces a rapid-acting insulin analogue. FDA approved on 1996. Insulin lispro 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 and catabolism. In humans, insulin is stored in the form of hexamers; however, only insulin monomers are able to interact with IR. Reversal of the proline and lysine residues at positions B28 and B29 of native insulin eliminates hydrophobic interactions and weakens some of the hydrogen bonds that contribute to the stability of the insulin dimers that comprise insulin hexamers. Hexamers of insulin lispro are produced in the presence of zinc and m-cresol. These weakly associated hexamers quickly dissociate upon subcutaneous injection and are absorbed as monomers through vascular endothelial cells. These properties give insulin lispro its fast-acting properties.
Dược Động Học :
▧ Absorption :
Rapidly absorbed following subcutaneous administration. It is also absorbed more quickly than regular human insulin. Peak serum levels occur 30-90 minutes after injection in healthy subjects. Absorption also differs depending on the site of injection. After insulin lispro was administered in the abdomen, serum drug levels were higher and the duration of action was slightly shorter than after deltoid or thigh administration. Bioavailability, 0.1 - 0.2 unit/kg = 55% - 77%.
▧ Volume of Distribution :
When administered intravenously as bolus injections of 0.1 and 0.2 U/kg dose in two separate groups of healthy subjects, the mean volume of distribution of insulin lispro appeared to decrease with increase in dose (1.55 and 0.72 L/kg, respectively).
▧ Metabolism :
Insulin is predominantly cleared by metabolic degradation via a receptor-mediated process.
▧ Half Life :
SubQ administration = 1 hour
▧ Clearance :
Clearance is dose dependent. When a dose of 0.1 unit/kg and 0.2 unit/kg were administered intravenously, the mean clearance was 21.0 mL/min/kg and 9.6 mL/min/kg respectively.
Độc Tính : 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. Rare cases of lipoatrophy or lipohypertrophy reactions have been observed.
Chỉ Định : For the treatment of Type 1 or 2 diabetes mellitus. To be used in conjunction with an intermediate or long-acting insulin except when used in a continuous insulin infusion pump.
Tương Tác Thuốc :
  • Acebutolol The beta-blocker, acebutolol, may decrease symptoms of hypoglycemia.
  • Atenolol The beta-blocker, atenolol, may decrease symptoms of hypoglycemia.
  • Bisoprolol The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.
  • Carvedilol The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
  • Dextropropoxyphene Concomitant therapy with drugs that may increase the blood-glucose-lowering effect of insulin lispro and thus the chance of hypoglycemia should be monitored closely.
  • Disopyramide Concomitant therapy with drugs that may increase the blood-glucose-lowering effect of insulin lispro and thus the chance of hypoglycemia should be monitored closely.
  • Enalapril Concomitant therapy with ACE inhibitors may increase the blood-glucose-lowering effect of insulin lispro and thus the chance of hypoglycemia should be monitored closely.
  • Epinephrine Concomitant therapy with sympathomimetic agents may reduce the blood-glucose-lowering effect of insulin lispro.
  • Esmolol The beta-blocker, esmolol, may decrease symptoms of hypoglycemia.
  • Fenofibrate Concomitant therapy with drugs that may increase the blood-glucose-lowering effect of insulin lispro and thus the chance of hypoglycemia should be monitored closely.
  • Fluoxetine Concomitant therapy with drugs that may increase the blood-glucose-lowering effect of insulin lispro and thus the chance of hypoglycemia should be monitored closely.
  • Hydrochlorothiazide Concomitant therapy with diuretics may reduce the blood-glucose-lowering effect of insulin lispro.
  • Losartan Concomitant therapy with angiotensin II receptor blockers may increase the blood-glucose-lowering effect of insulin lispro and thus the chance of hypoglycemia should be monitored closely.
  • Octreotide Concomitant therapy with somatostatin analogs may increase the blood-glucose-lowering effect of insulin lispro and thus the chance of hypoglycemia should be monitored closely.
  • Pentoxifylline Concomitant therapy with drugs that may increase the blood-glucose-lowering effect of insulin lispro and thus the chance of hypoglycemia should be monitored closely.
  • Pramlintide Concomitant therapy with drugs that may increase the blood-glucose-lowering effect of insulin lispro and thus the chance of hypoglycemia should be monitored closely.
  • Prednisone Concomitant therapy with corticosteriods may reduce the blood-glucose-lowering effect of insulin lispro.
  • Ramipril Concomitant therapy with ACE inhibitors may increase the blood-glucose-lowering effect of insulin lispro and thus the chance of hypoglycemia should be monitored closely.
Liều Lượng & Cách Dùng : Injection, solution - Subcutaneous - 100 units/ml
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty : Eli Lilly
    Sản phẩm biệt dược : Humalog
  • Công ty : Eli Lilly
    Sản phẩm biệt dược : Humalog KwikPen
  • Công ty : Eli Lilly
    Sản phẩm biệt dược : Humalog Pen
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00046
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D04477
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0002-7510-01
PharmGKB
http://www.pharmgkb.org/drug/PA164747059
Wikipedia
http://en.wikipedia.org/wiki/Insulin_lispro
RxList
http://www.rxlist.com/cgi/generic/insulinlispro.htm
Drugs.com
http://www.drugs.com/mtm/insulin-lispro.html
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