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General Description:

Reslizumab, identified by CAS number 241473-69-8, is a notable compound with significant therapeutic applications. Reslizumab is a humanized interleukin-5 (IL-5) antagonist monoclonal antibody (IgG4 kappa) that is produced by recombinant DNA technology in murine myeloma non-secreting 0 (NS0) cells. IL-5 is a pro-inflammatory cytokine that is responsible for the growth and differentiation, recruitment, activation, and survival of eosinophils . Elevated levels of eosinophils increase the risk for asthma exacerbations, including both allergic forms and nonallergic forms of asthma where eosinophilia is prominent. By targeting the IL-5 and disrupting its signalling pathways, reslizumab aims to inhibit eosinophil maturation and promote programmed cell death . Asthma is a chronic respiratory disease that causes inflammation in the lungs with asthma attacks that lead to severe breathing difficulties. Patients often experience persistent or exacerbating symptoms overtime despite conventional first-line therapies available. Inflammation-predominant asthma, which is chatacterized by eosinophilic infiltration of airway mucosa and elevated levels of eosinophils in the blood, sputum and BAL fluid, is associated with an increased risk for recurrent exacerbation and asthma-related hospitalizations . In four double-blind, randomized, placebo‑controlled trials in patients with severe asthma on currently available therapies, patients receiving reslizumab had fewer asthma attacks, and a longer time to the first attack compared to patients receiving placebo . In addition, a significant improvement in lung function was seen, as measured by the volume of air exhaled by patients in one second . Studies demonstrated that reslizumab was not effective in various asthma outcomes in patients without eosinophilia . Reslizumab was developed by Teva Pharmaceuticals. Approved by the FDA in March 2016, reslizumab is marketed under the brand name Cinqair for intravenous injection. It is injected once every four weeks via intravenous infusion. Cinqair is indicated as an add-on maintenance therapy for adults with severe asthma with an eosinophilic phenotype. It is approved for patients who have a history of severe asthma attacks (exacerbations) despite receiving their current asthma medicines. Reslizumab is marketed as Cinqaero in Europe.

Indications:

This drug is primarily indicated for: Indicated for the add-on maintenance treatment of patients with severe asthma aged 18 years and older with an eosinophilic phenotype. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Reslizumab undergoes metabolic processing primarily in: Like other monoclonal antibodies, reslizumab is assumed to undergo enzymatic proteolysis into smaller peptides and amino acids. As reslizumab bind to the target, it is not expected to undergo a target-mediated clearance . This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Reslizumab are crucial for its therapeutic efficacy: The peak serum concentrations of reslizumab were typically observed at the end of the infusion with the serum concentrations gradually declining from the peak in a biphasic manner. Following multiple doses, serum concentrations of reslizumab accumulated approximately 1.5 to 1.9-fold. Interindividual variability in peak and overall exposure across healthy individuals, patients with asthma, and other populations in pharmacokinetic studies was around 20-30% . Systemic exposure to reslizumab appeared to be unaffected by the presence of treatment-emergent anti-reslizumab antibodies. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Reslizumab is an important consideration for its dosing schedule: The half-life is approximately 24 days . This determines the duration of action and helps in formulating effective dosing regimens.

Volume of Distribution:

Reslizumab is distributed throughout the body with a volume of distribution of: The approximate volume of distribution of reslizumab is 5L, suggesting minimal distribution to the extravascular tissues . This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Reslizumab is a critical factor in determining its safe and effective dosage: Reslizumab clearance was approximately 7 mL/hour . It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Reslizumab exerts its therapeutic effects through: A reduction in blood eosinophil counts was observed in clinical studies following an initial infusion of 3 mg/kg reslizumab and was maintained through 52 weeks of treatment with no signs of tachyphylaxis. Greater reductions of blood eosinophils were observed in subjects with higher reslizumab serum concentrations. This effect was independent of the presence of treatment-emergent anti-reslizumab antibodies . The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Reslizumab functions by: Reslizumab an interleukin-5 (IL-5) antagonist (IgG4, kappa) that binds to IL-5 with a dissociation constant of 81 pM. IL-5 is a proinflammatory cytokine responsible for the terminal maturation of eosinophils and increases chemotaxis, endothelial adhesion, activation and survival of eosinophils. Eosinophils are known to play a central role in the pathophysiology of many patients with asthma; upon activation, eosinophils release leukotrienes, platelet activation factor, major basic protein, eosinophil cationic protein, eosinophil peroxidase, eosinophil-derived neurotoxin, and other cytokines that are cytotoxic to the bronchial epithelium and lead to airway inflammation and bronchospasm . IL-5 production is increased by upon activation of TH2 lymphocytes after antigen exposure and IL-5 stimulates the production and maturation of eosinophil precursors in the bone marrow . IL-5 promotes the growth and differentiation, recruitment, activation, and survival of eosinophils via interacting with the IL-5 receptor expressed on the eosinophil surface . Increased production and activation of eosinophils is especially prominent in nonallergic forms of asthma . Reslizumab is a humanized monoclonal antibody that occupies the region ERRR (glutamic acid, arginine, arginine, arginine) corresponding to amino acids 89–92 on IL-5, which is a region critical for its interaction with the IL-5 receptor on the eosinophil surface . By binding to IL-5 and disrupting its binding to the alpha chain of the IL-5 receptor complex, reslizumab inhibits the bioactivity of IL-5 and attenuates IL-5 signaling. Blocking of IL-5 signalling thereby reduces the production and survival of eosinophils and inhibits eosinophilic-driven inflammation. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Reslizumab 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:

Reslizumab is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Anti-Asthmatic Agents, Antibodies, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Blood Proteins, Drugs for Obstructive Airway Diseases, Globulins, Immunoglobulins, Immunoproteins, Interleukin Antagonists, Interleukin-5 Antagonist, Proteins, Respiratory System Agents, Serum Globulins. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Reslizumab include:

• Molecular Weight: 147000.0