| Primary information |
|---|
| ID | 1535 |
| ThPP ID | Th1114 |
| Therapeutic Peptide/Protein Name | Preotact |
| Sequence | Parathyroid hormone SVSEIQLMHNLGKHLNSMERVEWLRKKLQ view full sequnce in fasta |
| Functional Classification | Ib |
| Molecular Weight | 9420 |
| Chemical Formula | C408H674N126O126S2 |
| Isoelectric Point | N.A. |
| Hydrophobicity | N.A. |
| Melting Point (℃) | N.A. |
| Half Life | 1.5 hrs |
| Description | Recombinant, pharmaceutical form of parathyroid hormone (PTH), which is a single-chain polypeptide composed of 84 amino acids. Its sequence is identical to the full-length native 84-amino acid PTH polypeptide. It lacks disulfide bonds and glycosylation sites. Preotact is marketed in Europe by Nycomed. Preos is a registered trade mark owned by NPS Pharmaceuticals, Inc. The name Preos and the New Drug Application is pending approval by the U.S. Food and Drug Administration (FDA). |
| Indication/Disease | For use/treatment in osteoporosis. |
| Pharmacodynamics | Parathyroid hormone is responsible for the fine regulation of serum calcium concentration on a minute-to-minute basis. This is achieved by the acute effects of the hormone on calcium resorption in bone and calcium reabsorption in the kidney. The phosphate mobilized from bone is excreted into the urine by means of the hormone's influence on renal phosphate handling. Parathyroid hormone also stimulates calcium absorption in the intestine, this being mediated indirectly by 1,25-dihydroxyvitamin D. Thus, a hypocalcemic stimulus of parathyroid hormone secretion results in an increased influx of calcium from three sources (bone, kidney, and intestine), resulting in a normalization of the serum calcium concentration without change in the serum phosphate concentration. |
| Mechanism of Action | The biological actions of rhPTH are mediated through binding to at least two distinct high- affinity cell-surface receptors specific for the N-terminal and C-terminal regions of the molecule, both of which are required for normal bone metabolism. The N-terminal portion of the molecule is primarily responsible for the bone building effects of parathyroid hormone. The C-terminal portion of the molecule has antiresorptive activity and is necessary for normal regulation of N-terminal fragment activity. |
| Toxicity | N.A. |
| Metabolism | PTH is metabolised in the liver and to a lesser extent in the kidney. Parathyroid hormone is efficiently removed from the blood by a receptor-mediated process in the liver and is broken down into smaller peptide fragments. The fragments derived from the amino-terminus are further degraded within the cell while the fragments derived from the carboxy-terminus are released back into the blood and cleared by the kidney. These carboxy-terminal fragments are thought to play a role in the regulation of PTH activity. Under normal physiological conditions full-length PTH constitutes only 5-30% of the circulating forms of the molecule, while 70-95% is present as carboxy-terminal fragments. Following administration of Preotact, carboxy-terminal fragments make up about 60-90% of the circulating forms of the molecule. Intersubject variability in systemic clearance is about 15%. |
| Absorption | The absolute bioavailability of 100 micrograms of Preotact after subcutaneous administration in the abdomen is 55%. |
| Volume of Distribution | The volume of distribution at steady-state following intravenous administration is approximately 5.4 liters. Intersubject variability is about 40%. |
| Clearance | PTH is rapidly cleared from plasma, primarily by Kupffer cells in the liver. To a lesser extent, PTH is cleared by filtration and reabsorption by the kidney. |
| Categories | N.A. |
| Patents Number | N.A. |
| Date of Issue | N.A. |
| Date of Expiry | N.A. |
| Drug Interaction | N.A. |
| Target | Parathyroid hormone/parathyroid hormone-related peptide receptor,Parathyroid hormone 2 receptor |
| Information of corresponding available drug in the market |
|---|
| Brand Name | Preotact |
| Company | Nycomed |
| Brand Discription | pharmaceutical form of parathyroid hormone (H05AA03) manufactured using a strain of Escherichia coli modified by recombinant DNA technology. Preotact is used to treat osteoporosis in women past menopause with high risk of fractures. Osteoporosis is a disease that causes bones to become thin and fragile. It is especially common in women after the menopause. The disease progresses gradually so you may not feel any symptoms at first. But if you have osteoporosis, it makes you more likely to break bones, especially in your spine, hips and wrists. It may also cause back pain, loss of height, and a curved back. Preotact reduces the risk of breaking spinal bones because it increases your bone quality and strength. |
| Prescribed for | osteoporosis in women past menopause |
| Chemical Name | N.A. |
| Formulation | N.A. |
| Physcial Appearance | N.A. |
| Route of Administration | Subcutaneous |
| Recommended Dosage | 100 micrograms given once a day. Your doctor may advise you to take supplementary calcium and vitamin D. |
| Contraindication | Do not use Preotact: if you are allergic (hypersensitive) to parathyroid hormone or any of the other ingredients of Preotact; if you have had radiation therapy to the skeleton; if you suffer from high calcium levels and other disturbances in the calcium-phosphor metabolism; if you have other bone disease (including hyperparathyroidism or Paget’s disease); if you have high levels of alkaline phosphatase; if you suffer from severe kidney problems; if you suffer from severe liver disease. |
| Side Effects | increased level of calcium in the blood, increased level of calcium in the urine, and nausea. back pain, constipation, decreased muscle strength, diarrhoea, dizziness, erythema at injection site, fast or irregular heart beats, headache, muscle cramps, pain in extremity, stomach upset, tiredness, and vomiting. |
| Useful Link | http://en.wikipedia.org/wiki/Preotact http://www.diagnosia.com/en/drug/preotact-100-micrograms-powder-and-solvent-solution-injection http://www.firstwordpharma.com/node/1065956#axzz3TyRJJpfa http://www.medicaldevicesummit.com/Resource.ashx?sn=Preotactpendesignpaper |
| PubMed ID | 21524248, 21524246, 21155613, 20739387, 19189037 |
| 3-D Structure | Th1114 (View) or (Download) |