| Primary information |
|---|
| ThPP ID | Th1140 |
| Therapeutic Peptide/Protein Name | Insulin,isophane |
| Sequence | A chain: GIVEQCCTSICSLYQLENYCN B chain: FVNQHLCGS view full sequnce in fasta |
| Functional Classification | Ia |
| Molecular Weight | 5808 |
| Chemical Formula | C257H383N65O77S6 |
| Isoelectric Point | 9 |
| Hydrophobicity | N.A. |
| Melting Point (℃) | N.A. |
| Half Life | N.A. |
| Description | Recombinant (E.coli derived), Intermediate-acting insulin to improve glycemic control. It consists of a crystalline suspension of human insulin with protamine and zinc, which results in an intermediate-acting insulin with a slower onset of action and longer duration of activity compared to regular human insulin. |
| Indication/Disease | Used to improve glycemic control in patients with type 1 or type 2 diabetes mellitus. |
| Pharmacodynamics | When 0.3 Units/kg of NPH insulin was subcutaneously administered, the onset of action was approximately 0.8 hours. The duration of action was 13.2 hours. The peak activity of NPH insulin occurs 4-6 hours post-dose. Compared to insulin glargine, NPH insulin has a quicker onset of action and shorter duration of action. |
| Mechanism of Action | The primary activity of insulin is the regulation of glucose metabolism. Insulin promotes glucose and amino acid uptake into muscle and adipose tissues, and other tissues except brain and liver. It also has an anabolic role in stimulating glycogen, fatty acid, and protein synthesis. Insulin inhibits gluconeogenesis in the liver. Insulin 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 is able to autophosphorylate and phosphorylate numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. These activated proteins, in turn, lead 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) which play a critical role in metabolism and catabolism |
| Toxicity | Hypoglycemia is one of the most frequent adverse events experienced by insulin users. |
| Metabolism | Insulin is predominantly cleared by metabolic degradation via a receptor-mediated process. |
| Absorption | NPH insulin is generally well and rapidly absorbed from the site of injection. Absorption does not differ if it is subcutaneously administered in the thigh or abdomen. when 0.5 IU/kg of NPH insulin was given to adult type 1 diabetes patients before breakfast, the pharmacokinetic parameters are as follows: AUC (0-24hours) = 111,941 ± 77,941 pmol · l-1 · min-1; Cmax = 149 ± 121 pmol/l; Tmax = 480 ± 237 minute. It is important to note that NPH insulin has a high degree of patient variability in its absorption profile. |
| Volume of Distribution | 0.15 L/kg |
| Clearance | N.A. |
| Categories | Hypoglycemic Agents and Antidiabetic Agents |
| Patents Number | N.A. |
| Date of Issue | N.A. |
| Date of Expiry | N.A. |
| Drug Interaction | N.A. |
| Target | Insulin receptor |
| Information of corresponding available drug in the market |
|---|
| Brand Name | Novolin N |
| Company | Novo Nordisk |
| Brand Discription | It is an intermediate-acting insulin administered to control blood sugar level in diabetic patient. It was created by adding neutral protamine to regular procine insulin. Insulin isophane is a man-made form of a hormone that is produced in the body. It works by lowering levels of glucose (sugar) in the blood. Insulin isophane is a long-acting form of insulin that is slightly different from other forms of insulin that are not man-made. Insulin isophane is used to treat diabetes. Insulin isophane may also be used for purposes not listed in this medication guide. This package contains Novolin N in an InnoLet disposable prefilled insulin syringe. Novolin N is commonly known as NPH, Human Insulin Isophane Suspension (recombinant DNA origin). The concentration of this product is 100 units of insulin per milliliter. It is a cloudy or milky suspension of human insulin with protamine and zinc. The insulin substance (the cloudy material) settles at the bottom of the insulin reservoir, therefore, the Novolin N InnoLet (nph, human insulin isophane suspension 3 ml disposable prefilled syringe) must be rotated up and down so that the contents are uniformly mixed before a dose is given. Novolin N has an intermediate duration of action. The effect of Novolin N begins approximately 1½ hours after injection. The effect is maximal between 4 and 12 hours. The full duration of action may last up to 24 hours after injection. The time course of action of any insulin may vary considerably in different individuals, or at different times in the same individual. Because of this variation, the time periods listed here should be considered as general guidance only. This human insulin (recombinant DNA origin) is structurally identical to the insulin produced by the human pancreas. This human insulin is produced by recombinant DNA technology utilizing Saccharomyces cerevisiae (bakers' yeast) as the production organism. |
| Prescribed for | Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus, |
| Chemical Name | N.A. |
| Formulation | Novolin N in an InnoLet disposable prefilled insulin syringe. Novolin N is commonly known as NPH, Human Insulin Isophane Suspension (recombinant DNA origin). The concentration of this product is 100 units of insulin per milliliter. It is a cloudy or milky suspension of human insulin with protamine and zinc. The insulin substance (the cloudy material) settles at the bottom of the insulin reservoir, therefore, the Novolin N InnoLet (nph, human insulin isophane suspension 3 ml disposable prefilled syringe) must be rotated up and down so that the contents are uniformly mixed before a dose is given |
| Physcial Appearnce | Novolin N InnoLet (nph, human insulin isophane suspension 3 ml disposable prefilled syringe) |
| Route of Administration | Subcutaneous |
| Recommended Dosage | 0.5 U/kg/day SC (Type 1 Diabetes Mellitus), 0.5-1 units/kg/day in divided doses (Type 2 Diabetes Mellitus) |
| Contraindication | Tell your doctor or pharmacist if you have any medical conditions, pregnant, planning to become pregnant, or are breast-feeding; taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement; allergies to medicines, foods, or other substances; drink alcoholic beverages or smoke; heart problems (eg, heart failure); kidney or liver problems; nerve problems; adrenal, pituitary, or thyroid problems; or diabetic ketoacidosis; use 3 or more insulin injections per day; if you are fasting, have high blood sodium levels, or are on a low-salt (sodium) diet. Some MEDICINES MAY INTERACT with insulin isophane vials. Tell your health care provider if you are taking any other medicines, especially any of the following: Beta-blockers, Angiotensin-converting enzyme, (ACE) inhibitors, Thiazolidinediones Corticosteroids . |
| Side Effects | insulin allergy, Hypoglycemia, or low blood sugar, is the most common side effect of insulin. Symptoms of low blood sugar may include headache, hunger, sweating, pale skin, irritability, dizziness, feeling shaky, or trouble concentrating. Watch for signs of low blood sugar. Carry a piece of non-dietetic hard candy or glucose tablets with you in case you have low blood sugar. Tell your doctor if you have itching, swelling, redness, or thickening of the skin where you inject insulin isophane. |
| Useful Link | http://en.wikipedia.org/wiki/NPH_insulin http://www.drugs.com/mtm/insulin-isophane.html http://reference.medscape.com/drug/humulin-70-30-novolin-70-30-insulin-isophane-human-insulin-regular-human-999708 |
| PubMed ID | US4430266 |
| 3-D Structure | Th1140 A chainor (Download)Th1140 B chain (View) or (Download) |