Bulevirtide API Manufacturers

General Description:

Bulevirtide, identified by CAS number 2012558-47-1, is a notable compound with significant therapeutic applications. Hepatitis D is considered the most severe type of viral hepatitis and leads to the rapid development of cirrhosis, severe decompensation of liver function, and an increased risk of mortality. Until recently, there have been extremely limited treatments available for Hepatitis D infection. Bulevirtide, also known as Hepcludex, is a first-in-class entry inhibitor for the treatment of chronic Hepatitis D infection developed by MYR Pharmaceuticals, now part of Gilead. It was first approved for use in the EU on May 28, 2020; bulevirtide has been granted PRIME scheme eligibility and Orphan Drug Designation by the European Medicines Agency. In the USA, bulevirtide has been granted Orphan Drug Designation and Breakthrough Therapy Designation. Due to potentially beneficial synergistic effects in treating chronic Hepatitis D, bulevirtide is also under investigation in clinical trial NCT03852433 (Phase 2b Study of Bulevirtide With ) in Patients With CHD. Completion of this clinical trial is anticipated in early 2023.

Indications:

This drug is primarily indicated for: Bulevirtide is indicated for the treatment of chronic Hepatitis D infection in HDV-RNA positive adult patients with compensated liver disease. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Bulevirtide undergoes metabolic processing primarily in: To date, metabolism studies have not been conducted on bulevirtide. It is expected to be catabolized by peptidases to smaller peptides and amino acids, with no active metabolites. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Bulevirtide are crucial for its therapeutic efficacy: Human pharmacokinetic data for bulevirtide is limited in the literature. In rats, bulevirtide administered by subcutaneous injection is rapidly absorbed with a Cmax of 4 to 6 hours. The estimated bioavailability is 85% in humans, and steady-state concentrations are expected to occur within weeks of initiating treatment. The AUC for bulevirtide after a 2mg subcutaneous dose was found to be approximately 46 ng/ml.h with a Tmax of 0.5 hours. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Bulevirtide is an important consideration for its dosing schedule: The half-life of bulevirtide ranges between 4 and 7 hours in healthy adults. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Bulevirtide exhibits a strong affinity for binding with plasma proteins: The plasma protein binding of bulevirtide is >99%, and it is primarily bound to albumin. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Bulevirtide from the body primarily occurs through: Elimination through target (NTCP) binding is expected to be the main route of elimination for bulevirtide. In healthy volunteers, bulevirtide was not found to be excreted in the urine. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Bulevirtide is distributed throughout the body with a volume of distribution of: The volume of distribution of bulevirtide is estimated to be lower than total body water. In animals, bulevirtide distributes into the liver, gastrointestinal tract, kidney, and bladder. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Bulevirtide is a critical factor in determining its safe and effective dosage: The clearance after of bulevirtide after subcutaneous administration (CL/F) in healthy volunteers ranged from 7.98 L/h (±2.02) to 62 L/h (±16.7), depending on the dose administered. The clearance of bulevirtide decreases as the dose increases. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Bulevirtide exerts its therapeutic effects through: Bulevirtide prevents Hepatitis D entry into cells. It is effective in the reduction of Hepatitis D virus (HDV) RNA levels and improvement of liver inflammation in cases of Hepatitis D infection. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Bulevirtide functions by: The sodium taurocholate co-transporting polypeptide (NTCP) serves to transport bile acids in the sodium salt form to the liver from the portal circulation. It is an important component of enterohepatic circulation. The Hepatitis D virus replicates independently within liver cells but requires the hepatitis B surface antigen in order to propagate. Hepatitis B and D viruses enter hepatocytes through the binding of NTCP (sodium/taurocholate cotransporting polypeptide) to the Hepatitis B virus preS1 surface protein domain. Bulevirtide binds and subsequently inactivates the hepatitis B (HBV) and HDV receptors on hepatocytes. Bulevirtide blocks the NTCP binding site, subsequently blocking the entry of the viruses into cells. This prevents viral entry and replication, reducing symptoms of Hepatitis D infection. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Bulevirtide 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:

Bulevirtide is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Antiinfectives for Systemic Use, Antiviral Agents, Antivirals for Systemic Use, Direct Acting Antivirals, Lipids, Peptides. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.