Turoctocog alfa API Manufacturers

General Description:

Turoctocog alfa, identified by CAS number 1192451-26-5, is a notable compound with significant therapeutic applications. Turoctocog alfa is a recombinant factor VIII (rFVIII) with a truncated B-domain made from the sequence coding for 10 amino acids from the N-terminus and 11 amino acids from the C-terminus of the naturally occurring B-domain. Turoctocog alfa is produced in Chinese hamster ovary (CHO) cells without addition of any human- or animal-derived materials. During secretion, some rFVIII molecules are cleaved at the C-terminal of the heavy chain (HC) at amino acid 720, and a monoclonal antibody binding C-terminal to this position is used in the purification process allowing isolation of the intact rFVIII. It was developped by Novo Nordisk and FDA approved in October 16, 2013.

Indications:

This drug is primarily indicated for: Turoctocog alfa is indicated for the treatment and prophylaxis of bleedings in patients presenting hemophilia A. The treatment with turoctocog alfa is related with its use to control bleeding episodes or as a perioperative management. Hemophilia A is a hereditary hemorrhagic disorder generated by the congenital deficit of the coagulation factor VIII. This disease is manifested as excessive spontaneous or trauma-driven bleeding. The coagulation factor VIII is a robust initiator of thrombin which is later required for the generation of fibrin to form a platelet plug and its gene is expressed in the X chromosome. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Turoctocog alfa undergoes metabolic processing primarily in: Turoctocog alfa is expected to be cleaved by proteolysis into small individual aminoacids that constitute them after receptor mediated cell endocytosis. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Turoctocog alfa are crucial for its therapeutic efficacy: In pre-clinical studies, the absorption half-life was reported wot be 5.4 hours. The absorption profile varies depending on the age of the patient where the AUC is 9.92, 11.09 and 15.26 IU hour/ml for the age range of 0-6 years, 6-12 years and over 12 years old respectively. The Cmax according to the different age groups is 1, 1.07 and 1.226 IU/ml for the age range of 0-6 years, 6-12 years and over 12 years old respectively. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Turoctocog alfa is an important consideration for its dosing schedule: In pre-clinical studies, turoctocog half-life was reported to be 16 hours. In knockout mice there are reports of half-life of 7-8 hours. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Turoctocog alfa exhibits a strong affinity for binding with plasma proteins: Because turoctocog alfa is a recombinant protein, there has been not enough studies of protein binding. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Turoctocog alfa from the body primarily occurs through: After intravenous administration of turoctocog alfa, the time for complete elimination of the blood plasma is of 50-55 hours. Due to the fact that this drug is a 166 kDa, it is thought that it will be eliminated by tissue mechanisms such as receptor mediated endocytosis followed by catabolism rather than hepatic metabolism and renal excretion. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Turoctocog alfa is distributed throughout the body with a volume of distribution of: In pre-clinical studies, turoctocog distribution was studied based on a two model compartment and it resulted in 59 ml/kg in the central compartment and 13 ml/kg in the peripheral compartment. It also presented an inter-compartmental flow of 0.66 ml/hour kg. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Turoctocog alfa is a critical factor in determining its safe and effective dosage: In pre-clinical studies, turoctocog clearance was reported to be 6.5 ml/hour kg. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Turoctocog alfa exerts its therapeutic effects through: After turoctocog alfa administration, it has been reported a significant improvement in hemostasis. This effect was observed by the amelioration on whole blood clotting time. In clinical trials, there were no reports of development of factor VIII inhibitors and even 90% of the ocurred bleeds were resolved with 1 or 2 infusions of turoctocog alfa. There are no reports of treatment failure. In vitro studies confirmed the ability of turoctocog alfa to improve clot formation and clot stability. All these studies prove that turoctocog alfa is fully functional and its activity is similar to the one showed by other recombinant factor VIII products. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Turoctocog alfa functions by: The B domain is known to perform the function of restrict the expression of the endogenous coagulation factor VIII but it has no direct relationship to the function of this factor. In normal conditions during hemostasis, the coagulation factor VIII will be activated by specific thrombin cleavages producing A1, A2 and A3-C1-C2 fragments of activated factor VIII (Factor VIIIa) which will form a complex with the factor IXa and activate the factor X leading to a stable haemostatic plug. Turoctocog contains all function-related domains with a considerably easier intact expression of the protein in mammalian cells by truncating the B domain. This recombinant structure allows it to replace the missing factor VIII and restore hemostasis. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Turoctocog alfa belongs to the None, classified under the direct parent group Peptides. This compound is a part of the Organic Compounds, falling under the Organic Acids superclass, and categorized within the Carboxylic Acids and Derivatives class, specifically within the Amino Acids, Peptides, and Analogues subclass.

Categories:

Turoctocog alfa is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Biological Factors, Blood Coagulation Factors, Blood Proteins, Hemostatics, Protein Precursors, Proteins, Recombinant Proteins. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Turoctocog alfa include:

• Water Solubility: Soluble
• Isoelectric Point: It does not posses a distinct value
• Molecular Weight: 166000.0
• Molecular Formula: C7480H11379N1999O2194S68