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General Description:

Crizanlizumab, identified by CAS number 1690318-25-2, is a notable compound with significant therapeutic applications. Crizanlizumab is a humanized IgG2 monoclonal antibody used to reduce the frequency of vaso-occlusive crises in patients with sickle cell disease. Sickle cell disease is a genetically inherited condition prevalent in the Middle East, Africa, and certain parts of India. The genetic mutation associated with this disease leads to the formation of abnormal, sickle shaped red blood cells that aggregate and block blood vessels throughout the body, causing vaso-occlusive crises. Sickle cell disease can lead to excruciating pain, stroke, infection, and various other complications arising from the blockage of blood vessels. Currently, patients are prescribed to raise levels of fetal hemoglobin as a method of reducing morbidity and mortality. Though hydroxyurea has been shown to reduce the frequency of vaso-occlusive crises, adherence to this therapy is difficult due to adverse effects and the high variability of response to the drug between patients. Crizanlizumab, or SEG101, is given once every 4 weeks and may improve patient adherence. It was developed by Novartis and was granted FDA approval on November 15, 2019.

Indications:

This drug is primarily indicated for: Crizanlizumab is indicated to reduce the frequency of vaso-occlusive crisis in patients with sickle cell diseases who are ≥16 years old. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Crizanlizumab undergoes metabolic processing primarily in: Crizanlizumab is expected to be metabolized into smaller peptides and amino acids. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Crizanlizumab are crucial for its therapeutic efficacy: Crizanlizumab reaches a C_max of 0.16mg/mL with an AUC of 34.6mg\*hr/mL. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Crizanlizumab is an important consideration for its dosing schedule: Given a 5mg/kg dose of crizanlizumab, the mean terminal elimination half life of crizanlizumab is 10.6 days in healthy subjects and 7.6 days in patients with sickle cell disease. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Crizanlizumab exhibits a strong affinity for binding with plasma proteins: Monoclonal antibodies are generally not protein bound. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Crizanlizumab from the body primarily occurs through: Monoclonal antibodies are eventually phagocytosed and broken down to smaller peptides and amino acids which are eliminated in a similar fashion to other proteins. Monoclonal antibodies are generally not eliminated in the urine, and only a small amount is excreted in bile. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Crizanlizumab is distributed throughout the body with a volume of distribution of: The volume of distribution of crizanlizumab is 4.26L. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Crizanlizumab is a critical factor in determining its safe and effective dosage: Given a 5mg/kg dose of crizanlizumab, the clearance rate is 11.7ml/hr in healthy subjects. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Crizanlizumab exerts its therapeutic effects through: Crizanlizumab is a P-selectin inhibitor that prevents interactions between endothelial cells, platelets, red blood cells, and leukocytes. It has a long duration of action as it is given every 4 weeks. Patients should be counselled regarding the risk of infusion reactions as well as crizanlizumab's interference with platelet counts using EDTA tubes. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Crizanlizumab functions by: Crizanlizumab binds to P-selectin on endothelial cells and platelets, preventing their interaction with P-selectin glycoprotein ligand 1 on endothelial cells, platelets, red blood cells, and leukocytes. By preventing this interaction, components of the blood are less likely to come together, causing a vaso-occlusive crisis in patients with sickle cell diseases. The median per year incidence of vaso-occlusive crises was 1.04 in the high-dose crizanlizumab group, 2.00 in the low-dose crizanlizumab group, and 2.08 in the placebo group. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Crizanlizumab 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:

Crizanlizumab is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Antibodies, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Blood and Blood Forming Organs, Blood Proteins, Globulins, Immunoglobulin G, Immunoglobulins, Immunoproteins, Proteins, 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 Crizanlizumab include:

• Molecular Weight: 146000.0