Golimumab API Manufacturers

General Description:

Golimumab, identified by CAS number 476181-74-5, is a notable compound with significant therapeutic applications. Golimumab is a human IgG1қ monoclonal antibody derived from immunizing genetically engineered mice with human TNFα. Golimumab binds and inhibits soluble and transmembrane human TNFα. Increased TNFα is associated with chronic inflammation. Thus golimumab is indicated for use in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) alone or as an adjunct to methotrexate treatment in patients with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS), and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. In the U.S. and Canada, golimumab is marketed under the brand name Simponi®. The FDA label includes a black box warning of serious infections and malignancy. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed.

Indications:

This drug is primarily indicated for: Used in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) in patients 2 years old and above with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS) or in combination with methotrexate, and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. It is also indicated (v) for the treatment of active polyarticular juvenile idiopathic arthritis (pJIA) in patients 2 years of age and older. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Golimumab undergoes metabolic processing primarily in: The metabolism of golimumab has yet to be determined. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Golimumab are crucial for its therapeutic efficacy: After subcutaneous administration, golimumab can achieve maximum serum concentrations in 2 to 6 days and has an approximate bioavailability of 53%. In healthy volunteers, the maximum average concentration reached was 3.2 ± 1.4 μg/mL. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Golimumab is an important consideration for its dosing schedule: Golimumab has a long half-life of about 2 weeks. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Golimumab exhibits a strong affinity for binding with plasma proteins: Plasma protein binding was not quantified. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Golimumab from the body primarily occurs through: The route of elimination for golimumab has yet to be determined. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Golimumab is distributed throughout the body with a volume of distribution of: After IV administration, golimumab has a volume of distribution of about 58 to 126 mL/kg. This means that golimumab stays mostly in the circulatory system. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Golimumab is a critical factor in determining its safe and effective dosage: After one IV dose of golimumab, the systemic clearance was about 4.9 to 6.7 mL/day/kg. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Golimumab exerts its therapeutic effects through: Golimumab inhibits the activity of the cytokine, tumor necrosis factor alpha (TNFα). In areas such as the joints and blood, increased TNFα is associated with chronic inflammation seen in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Thus golimumab decreases the inflammation in these conditions. Concerning ulcerative colitis, the physiological effects of golimumab has yet to be determined. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Golimumab functions by: As a human monoclonal antibody, golimumab binds and inhibits soluble and transmembrane human TNFα. Inhibition of TNFα prevents it binding to its receptors, which prevents both leukocyte infiltration through prevention of cell adhesion proteins such as E-selectin, ICAM-1 and VCAM-1, and pro-inflammatory cytokine secretion such as IL-6, IL-8, G-CSF and GM-CSF in vitro. Consequently, in patients with chronic inflammatory conditions, decreases in ICAM-1 and IL-6 as well as C-reactive protein (CRP), matrix metalloproteinase 3 (MMP-3), and vascular endothelial growth factor (VEGF) were observed. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Golimumab 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:

Golimumab is categorized under the following therapeutic classes: Agents reducing cytokine levels, Amino Acids, Peptides, and Proteins, Anti-Inflammatory Agents, Antibodies, Antibodies, Monoclonal, Antineoplastic and Immunomodulating Agents, Antirheumatic Agents, Biologics for Rheumatoid Arthritis Treatment, Blood Proteins, Disease-modifying Antirheumatic Agents, Globulins, Immunoglobulins, Immunologic Factors, Immunoproteins, Immunosuppressive Agents, Proteins, Serum Globulins, Tumor necrosis factor alpha (TNF-alpha) inhibitors, Tumor Necrosis Factor Blockers, Tumor Necrosis Factor Receptor Blocking Activity. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Golimumab include:

• Molecular Weight: 146943.1937
• Molecular Formula: C6530H10068N1752O2026S44