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Statements

Subject Item
n2:DB00046
rdf:type
n3:Drug
n3:description
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.
n3:dosage
n14:271B418C-363D-11E5-9242-09173F13E4C5 n14:271B418D-363D-11E5-9242-09173F13E4C5 n14:271B418E-363D-11E5-9242-09173F13E4C5
n3:generalReferences
# Miles HL, Acerini CL: Insulin analog preparations and their use in children and adolescents with type 1 diabetes mellitus. Paediatr Drugs. 2008;10(3):163-76. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/18454569 # Zib I, Raskin P: Novel insulin analogues and its mitogenic potential. Diabetes Obes Metab. 2006 Nov;8(6):611-20. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/17026485
n3:group
approved
n3:halfLife
SubQ administration = 1 hour
n3:indication
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.
n3:manufacturer
n4:271B417D-363D-11E5-9242-09173F13E4C5
owl:sameAs
n6:DB00046 n8:DB00046
dcterms:title
Insulin Lispro
adms:identifier
n16:D04477 n17:DB00046 n18:0002-7510-01 n22:PA164747059 n23:Insulin_lispro
n3:mechanismOfAction
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 <i>m</i>-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.
n3:packager
n4:271B417B-363D-11E5-9242-09173F13E4C5 n4:271B417C-363D-11E5-9242-09173F13E4C5 n4:271B4179-363D-11E5-9242-09173F13E4C5 n4:271B417A-363D-11E5-9242-09173F13E4C5 n4:271B4178-363D-11E5-9242-09173F13E4C5
n3:patent
n7:5514646 n7:5474978 n7:2151560 n7:2151564
n3:synonym
Insulin Lispro Recombinant
n3: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. Rare cases of lipoatrophy or lipohypertrophy reactions have been observed.
n3:volumeOfDistribution
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).
n19:hasAHFSCode
n21:68-20-08
n3:foodInteraction
Inject subcutaneuosly 15 minutes before meal
n3:mixture
n13:271B4174-363D-11E5-9242-09173F13E4C5 n13:271B4175-363D-11E5-9242-09173F13E4C5 n13:271B4176-363D-11E5-9242-09173F13E4C5 n13:271B4177-363D-11E5-9242-09173F13E4C5
foaf:page
n12:insulinlispro.htm n25:insulin-lispro.html
n3:Molecular-Formula
n10:271B4193-363D-11E5-9242-09173F13E4C5
n3:Molecular-Weight
n10:271B4192-363D-11E5-9242-09173F13E4C5
n19:hasATCCode
n20:A10AB04 n20:A10AD04 n20:A10AC04
n3: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%.
n3:affectedOrganism
Humans and other mammals
n3:casRegistryNumber
133107-64-9
n3:category
n3: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.
n3:containedIn
n9:271B4183-363D-11E5-9242-09173F13E4C5 n9:271B4184-363D-11E5-9242-09173F13E4C5 n9:271B4181-363D-11E5-9242-09173F13E4C5 n9:271B4182-363D-11E5-9242-09173F13E4C5 n9:271B417F-363D-11E5-9242-09173F13E4C5 n9:271B4180-363D-11E5-9242-09173F13E4C5 n9:271B417E-363D-11E5-9242-09173F13E4C5 n9:271B418B-363D-11E5-9242-09173F13E4C5 n9:271B4189-363D-11E5-9242-09173F13E4C5 n9:271B418A-363D-11E5-9242-09173F13E4C5 n9:271B4187-363D-11E5-9242-09173F13E4C5 n9:271B4188-363D-11E5-9242-09173F13E4C5 n9:271B4185-363D-11E5-9242-09173F13E4C5 n9:271B4186-363D-11E5-9242-09173F13E4C5
n3:Hydrophobicity
n10:271B4190-363D-11E5-9242-09173F13E4C5
n3:Isoelectric-Point
n10:271B4191-363D-11E5-9242-09173F13E4C5
n3:Melting-Point
n10:271B418F-363D-11E5-9242-09173F13E4C5