A database of FDA approved therapeutic peptides and proteins
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1520 details |
| Primary information | |
|---|---|
| ThPP ID | Th1107 |
| Therapeutic Peptide/Protein Name | Insulin glulisine |
| Sequence | A chainGIVEQCCTSICSLYQLENYCN B chainFVKQHLCGSHLVEA view full sequnce in fasta |
| Functional Classification | Ib |
| Molecular Weight | 5823 |
| Chemical Formula | C258H384N64O78S6 |
| Isoelectric Point | N.A. |
| Hydrophobicity | N.A. |
| Melting Point (℃) | N.A. |
| Half Life | Elimination half life= 42 minutes (SC injection) |
| Description | Insulin glulisine is a recombinant (E. Coli derived), rapid-acting analog of human insulin. It contains two mutations, one at position B3, where R is replaced by K and the other at position B29, where K is replaced by E. This results in decrease hexamer formation and increased stability of the monomer, thus increasing the rate of absorption and quicker action as compared to native insulin. |
| Indication/Disease | For the treatment of Type 1 and 2 diabetes mellitus. Should be used in regimens including a long-acting or basal insulin analogue unless it is used in a continuous infusion pump. May be used with oral antidiabetic agents. |
| 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. Postprandial insulin spikes are 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 glulisine is a rapid-acting insulin analogue used to mimic postprandial insulin spikes in diabetic individuals. The onset of action of insulin glulisine is approximately 15 minutes. Its activity peaks 60 minutes following subcutaneous injection and its duration of action is 2-4 hours. |
| Mechanism of Action | Insulin glulisine 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. Substitution of the arginine at position B3 for lysine and replacement of the B29 lysine with glutamic acid decreases the propensity to form hexamers, stabilizes the hormone in monomeric form and results in a rapid rate of absorption and short duration of action. |
| 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. |
| Metabolism | N.A. |
| Absorption | Compared to regular human insulin, insulin glulisine is faster absorbed. When 0.15 units/kg was subcutaneously administered to type 1 diabetes patients, the pharmacokinetic parameters are as follows: Tmax = 60 minutes (range of 40 - 120 minutes); Cmax = 83 microUnits/mL (range of 40 - 131 microUnits/mL). Absolute bioavailability following subcutaneous administration is approximately 70%, regardless of site of injection. |
| Volume of Distribution | 13 L |
| Clearance | N.A. |
| Categories | Antidiabetic Agents |
| Patents Number | US6960561 |
| Date of Issue | 26/01/07 |
| Date of Expiry | 26/01/27 |
| Drug Interaction | N.A. |
| Target | Insulin receptor |
| Information of corresponding available drug in the market | |
| Brand Name | APIDRA |
| Company | sanofi-aventis |
| Brand Discription | APIDRA (insulin glulisine [rDNA origin] injection) is a rapid-acting human insulin analog used to lower blood glucose. Insulin glulisine is produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli (K12). Insulin glulisine differs from human insulin in that the amino acid asparagine at position B3 is replaced by lysine and the lysine in position B29 is replaced by glutamic acid. Chemically, insulin glulisine is 3B-lysine29B-glutamic acid-human insulin, has the empirical formula C258H384N64O78S6 and a molecular weight of 5823 |
| Prescribed for | APIDRA is indicated to improve glycemic control in adults and children with diabetes mellitus. |
| Chemical Name | N.A. |
| Formulation | Each milliliter of APIDRA contains 100 units (3.49 mg) insulin glulisine, 3.15 mg metacresol, 6 mg tromethamine, 5 mg sodium chloride, 0.01 mg polysorbate 20, and water for injection. APIDRA has a pH of approximately 7.3. The pH is adjusted by addition of aqueous solutions of hydrochloric acid and/or sodium hydroxide |
| Physcial Appearnce | Sterile, aqueous, clear, and colorless solution |
| Route of Administration | N.A. |
| Recommended Dosage | APIDRA is a recombinant insulin analog that is equipotent to human insulin (i.e. one unit of APIDRA has the same glucose-lowering effect as one unit of regular human insulin) when given intravenously. When given subcutaneously, APIDRA has a more rapid onset of action and a shorter duration of action than regular human insulin. The dosage of APIDRA must be individualized. Blood glucose monitoring is essential in all patients receiving insulin therapy. The total daily insulin requirement may vary and is usually between 0.5 to 1 Unit/kg/day. Insulin requirements may be altered during stress, major illness, or with changes in exercise, meal patterns, or coadministered drugs. |
| Contraindication | APIDRA is contraindicated: during episodes of hypoglycemia, in patients who are hypersensitive to APIDRA or to any of its excipients When used in patients with known hypersensitivity to APIDRA or its excipients, patients may develop localized or generalized hypersensitivity reactions. |
| Side Effects | Hypoglycemia, Hypokalemia |
| Useful Link | http://www.rxlist.com/apidra-drug/side-effects-interactions.htm http://www.apidra.com/default.aspx http://www.drugs.com/pro/apidra.html |
| PubMed ID | 20429049, 20424816, 19496630, 18076215, 17764465, 17703632, 17316105, 16706558, 16193096 |
| 3-D Structure | Th1107 A chain or (Download),Th1107 B chain (View) or (Download) |