Nonacog beta pegol API Manufacturers

General Description:

Nonacog beta pegol, identified by CAS number 1175512-71-6, is a notable compound with significant therapeutic applications. Nonacog beta pegol is a recombinant coagulation factor IX derivative. It is produced without animal-derived materials and with an attached 40kDa polyethylene glycol (PEG) molecule for peptide activation by a site-directed glycoPEGylation. Once activated, the activation molecule with PEG is cleaved to leave the activated factor IX (Factor IXa). Nonacog beta pegol was developed by Novo Nordisk and received its first global approval by the FDA on May 31, 2017, followed by the European Commission approval on June 2, 2017. Nonacog beta pegol was approved by Health Canada on November 29, 2017.

Indications:

This drug is primarily indicated for: Nonacog beta pegol is indicated in adults and children with hemophilia B (congenital factor IX deficiency or Christmas disease) for control and prevention of bleeding episodes as well as control and prevention of bleeding in the perioperative setting. It is also used for routine prophylaxis to prevent or reduce the frequency of bleeding episodes. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Nonacog beta pegol undergoes metabolic processing primarily in: After being taken up by cells, the proteinic component of nonacog beta pegol is degraded by lysosomes or endosomes. The PEG component of the drug is retained in the body 7.5 to 9 times longer than the original compound, as it is returned to circulation. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Nonacog beta pegol are crucial for its therapeutic efficacy: The mean area under the curve (AUC)_inf ranged from 46 to 91 IU*hours/mL in children and adults. In preclinical studies, there was a reduced accumulation of systemic drug after multiple dosing. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Nonacog beta pegol is an important consideration for its dosing schedule: The mean half-life ranged from 70 to 89 hours in children and adults. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Nonacog beta pegol exhibits a strong affinity for binding with plasma proteins: Nonacog beta pegol is not expected to bind to plasma proteins. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Nonacog beta pegol from the body primarily occurs through: The 40 kDa PEG component of nonacog beta pegol is eliminated in urine and feces taking approximately 49 and 40% of the administered dose respectively. The PEG part of the drug seems to be eliminated with a bi-phasic profile that was registered at 2-3 days and at 15-18 days. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Nonacog beta pegol is distributed throughout the body with a volume of distribution of: The volume of distribution varies depending on the patient's age. After single administration, the volume of distribution goes from 72 ml/kg for children less than 6 years of age, 68 ml/kg for adolescents between 7 and 12 years of age, 59 ml/kg in adolescents between 13 and 17 years of age, and 47 ml/kg for adults. At steady state, the volume of distribution of nonacog beta pegol is 64 ml/kg. Nonacog beta pegol is not expected to accumulate in tissues. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Nonacog beta pegol is a critical factor in determining its safe and effective dosage: Mean clearance in children and adults ranged from 0.4 to 0.8 mL/hour/kg. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Nonacog beta pegol exerts its therapeutic effects through: After nonacog beta pegol is activated by the coagulation factor IXa and tissue-coagulation factor VIIa, the peptide is cleaved off. In preclinical studies, whole blood clotting time activity was restored and the activated-partial thromboplastin time returned to normal limits. In clinical trials, the administration of nonacog beta pegol significantly increased the levels of factor IX in plasma and temporarily corrected the level of activated partial thromboplastin time. The effect of nonacog beta pegol translated into good hemostasis when used to treat bleeding on demand. A reduction of annualized bleeding rates was also observed when used as prophylaxis without the formation of factor IX inhibitors, allergic reactions or thromboembolic complications. The reports in clinical trials have also shown a significant prolongation in the duration of the hemostatic effect. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Nonacog beta pegol functions by: Nonacog beta pegol is activated by factor IXa and the tissue complex factor VII, whereby the peptide, including the 40kDa PEG moiety, is cleaved off. The resulting product from this activation process is recombinant factor IX with the same biological activity as endogenous coagulation factor IXa. The activated coagulation factor IX, in combination with factor VIIIa, activates the coagulation factor X to trigger the coagulation cascade and promote the conversion of prothrombin into thrombin. Thrombin drives the conversion of fibrinogen into fibrin for clot formation. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Categories:

Nonacog beta pegol is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Biological Factors, Blood Coagulation Factors, Blood Proteins, Compounds used in a research, industrial, or household setting, Enzyme Precursors, Enzymes and Coenzymes, Hemostatics, Macromolecular Substances, Pegylated agents, Polymers, Protein Precursors, 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 Nonacog beta pegol include:

• Water Solubility: Soluble
• Molecular Weight: 98000.0
• Molecular Formula: C2041H3114N558O641S25