A database of FDA approved therapeutic peptides and proteins
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1684 details |
| Primary information | |
|---|---|
| ThPP ID | Th1164 |
| Therapeutic Peptide/Protein Name | Antithrombin Alfa |
| Sequence | NA view full sequnce in fasta |
| Functional Classification | Ia |
| Molecular Weight | 57,215 |
| Chemical Formula | C2191H3457N583O656S19 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting Point (℃) | NA |
| Half Life | 11.6 (84.7) for 50 IU/KG to17.7 (60.9) for 100IU/KG |
| Description | Antithrombin (Recombinant) and plasma-derived antithrombin both contain six cysteine residues forming three disulphide bridges and 3-4 N-linked carbohydrate moieties. The glycosylation profile of antithrombin (Recombinant) is different from plasma-derived antithrombin, which results in an increased heparin affinity. When assayed in the presence of excess of heparin the potency of the recombinant product is not different from that of plasma-derived product. |
| Indication/Disease | Indicated for the prevention of peri-operative and peri-partum thromboembolic events in hereditary antithrombin deficient patients |
| Pharmacodynamics | Hereditary AT deficiency causes an increased risk of venous thromboembolism (VTE). During high-risk situations such as surgery or trauma or for pregnant women, during the peripartum period, the risk of development of VTEs as compared to the normal population in these situations is increased by a factor 10 to 506,7. In hereditary antithrombin deficient patients ATryn restores (normalizes) plasma AT activity levels during peri-operative and peri-partum periods. |
| Mechanism of Action | Antithrombin (AT) plays a central role in the regulation of hemostasis. AT is the principal inhibitor of thrombin and Factor Xa5, the serine proteases that play pivotal roles in blood coagulation. AT neutralizes the activity of thrombin and Factor Xa by forming a complex which is rapidly removed from the circulation. The ability of antithrombin to inhibit thrombin and Factor Xa can be enhanced by greater than 300 to 1000 fold when AT is bound to heparin. |
| Toxicity | The toxicological profile of antithrombin (Recombinant) administered by the intravenous route as bolus injections and infusions has been evaluated in both single- and repeat-dose studies performed in rats, dogs, and monkeys across a range of doses from 2.1 to 360 mg/kg. The highest doses in the single dose toxicity studies in rats and dogs were 360 mg/kg and 210 mg/kg, respectively. Toxicities observed were limited to transient injection site swelling observed in rats and dogs at the highest doses tested, and increased AST at highest dose in the dog study, both resolved during recovery period. The highest dose in the 28-day repeated-dose toxicity study in rats was 360 mg/kg/day. The toxicity at this dose was limited to transient limb swelling and local injection site bruising and swelling. The highest dose in the 14-day repeated-dose toxicity study in monkeys was 300 mg/kg/day or approximately 7-8 times human dose. Toxicities observed in female monkeys at this dose included internal bleeding, hematological changes and liver toxicity, with one out of three female animals showing multifocal hepatic necrosis. Both sexes showed increased AST and ALK on day 15, with both parameters returning to normal by day 22. There was no adverse effect in monkeys dosed with 120 mg/kg/day. |
| Metabolism | NA |
| Absorption | NA |
| Volume of Distribution | NA |
| Clearance | NA |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | NA |
| Information of corresponding available drug in the market | |
| Brand Name | Atryn |
| Company | Gtc Biotherapeutics, Inc. |
| Brand Discription | ATryn is a nanofiltered, sterile, terminally heat treated, lyophilized dosage form. Antithrombin (Recombinant), active ingredient of ATryn, is a recombinant human antithrombin. It is a 432 amino acid glycoprotein with a molecular weight of approximately 57,215 Daltons. The molecular formula is: C2191H3457N583O656S18. Antithrombin (Recombinant) is produced by recombinant DNA technology using genetically engineered goats into which the DNA coding sequence for human antithrombin has been introduced along with a mammary gland specific DNA sequence, which directs the expression of the antithrombin into the milk. The goats in which antithrombin (Recombinant) is produced are USDA certified scrapie-free, and controlled for specific pathogens. |
| Prescribed for | It is indicated for the prevention of peri-operative and peri-partum thromboembolic events in hereditary antithrombin deficient patients |
| Chemical Name | NA |
| Formulation | 1750 [iU]/1 |
| Physcial Appearnce | injection, powder, lyophilized, for solution |
| Route of Administration | IV |
| Recommended Dosage | The dosage is to be individualized based on the patient's pre-treatment functional AT activity level (expressed in percent of normal) and body weight (expressed in kilograms) and using therapeutic drug monitoring |
| Contraindication | NA |
| Side Effects | Hemorrhage (intra-abdominal, hemarthrosis and post procedural) |
| Useful Link | http://www.rxlist.com/atryn-drug.htm |
| PubMed ID | 19141163 |
| 3-D Structure | N.A. |