| Primary information |
|---|
| ThPP ID | Th1152 |
| Therapeutic Peptide/Protein Name | Drotrecogin alfa |
| Sequence | Heavy Chain: LIDGKMTRRGDSPWQVVLLDSKKKLACGAVLIHPSWV view full sequnce in fasta |
| Functional Classification | Ib |
| Molecular Weight | 55000 |
| Chemical Formula | C1786H2779N509O519S29 |
| Isoelectric Point | 6.78 |
| Hydrophobicity | -0.291 |
| Melting Point (℃) | N.A. |
| Half Life | 5.5 Hrs (Mammalian reticulocytes,in vitro |
| Description | Drotrecogin alfa is activated human protein C that is synthesized by recombinant DNA technology. It is a glycoprotein of approximately 55 kilodalton molecular weight, consisting of a heavy chain and a light chain linked by a disulfide bond. Drotrecogin alfa was withdrawn from the market after a major study indicated that it was not effective in improving outcomes in patients with sepsis. |
| Indication/Disease | For reduction of mortality in patients with severe sepsis. |
| Pharmacodynamics | Drotrecogin alfa is activated human protein C that is synthesized by recombinant DNA technology. It is a glycoprotein of approximately 55 kilodalton molecular weight, consisting of a heavy chain and a light chain linked by a disulfide bond. Drotrecogin alfa inhibits factor Va and VIIIa, thereby reducing the coagulability of blood. |
| Mechanism of Action | Activated protein C combines with protein S on platelet surfaces and then degrades factor Va and factor VIIIa, thereby reducing blood coagulability. |
| Toxicity | N.A. |
| Metabolism | N.A. |
| Absorption | N.A. |
| Volume of Distribution | N.A. |
| Clearance | 40 L/hr- Severe sepsis adults, 30±8L/hr patients without sepsis undergoing haemodialysis, 28±9L/hr for healthy patients |
| Categories | Antisepsis |
| Patents Number | CA2036894 |
| Date of Issue | 15/01/02 |
| Date of Expiry | 22/02/11 |
| Drug Interaction | Clopidogrel, Enoxaprin, Dalteparin, Fondaparinux, Tinzaparin, enhance the adverse or toxic effect of drotrecogin alfa |
| Target | Coagulation factor VIII, V, Plasminogen activator inhibitor 1, Thrombomodulin, Vitamin K-dependent protein S, Ceruloplasmin, Prothrombin, Platelet factor 4, Plasma serine protease inhibitor, Serpin B6, Vitamin K-dependent gamma-carboxylase, Endothelial protein C receptor |
| Information of corresponding available drug in the market |
|---|
| Brand Name | Xigris |
| Company | Eli Lilly and Company |
| Brand Discription | Xigris (drotrecogin alfa (activated)) is a recombinant form of human activated protein C. An established human cell line possessing the complementary DNA for the inactive human protein C zymogen secretes the protein into the fermentation medium. Fermentation is carried out in a nutrient medium containing the antibiotic geneticin sulfate. Geneticin sulfate is not detectable in the final product. |
| Prescribed for | Xigris (drotrecogin alfa) is indicated for the reduction of mortality in adult patients with severe sepsis (sepsis associated with acute organ dysfunction) who have a high risk of death |
| Chemical Name | N.A. |
| Formulation | The 5 and 20 mg vials of Xigris contain 5.3 mg and 20.8 mg of drotrecogin alfa (activated), respectively. The 5 and 20 mg vials of Xigris (drotrecogin alfa) also contain 40.3 and 158.1 mg of sodium chloride, 10.9 and 42.9 mg of sodium citrate, and 31.8 and 124.9 mg of sucrose, respectively. |
| Physcial Appearnce | Xigris (drotrecogin alfa) is supplied as a sterile, lyophilized, white to off-white powder |
| Route of Administration | Intravenous Infusion |
| Recommended Dosage | Xigris (drotrecogin alfa) should be administered intravenously at an infusion rate of 24 mcg/kg/hr (based on actual body weight) for a total duration of infusion of 96 hours. Dose adjustment based on clinical or laboratory |
| Contraindication | Xigris (drotrecogin alfa) increases the risk of bleeding. Xigris (drotrecogin alfa) is contraindicated in the active internal bleeding, hemorraghic stroke, intracranial surgery, Trauma, Intracranial neospasm |
| Side Effects | Bleeding is the most commonly reported adverse reaction in patients receiving Xigris therapy |
| Useful Link | http://www.rxlist.com/xigris-drug.htm |
| PubMed ID | 22616830, 16333441 |
| 3-D Structure | Th1152 (View) or (Download) |