Risankizumab API Manufacturers

General Description:

Risankizumab, identified by CAS number 1612838-76-2, is a notable compound with significant therapeutic applications. Risankizumab is a fully humanized IgG1 monoclonal antibody (mAb) directed against interleukin 23 (IL-23). It gained its first global approval in Japan in March 2019, followed by approval in Canada, the US, and Europe in April 2019. Risankizumab is used to treat plaque psoriasis, psoriatic arthritis, and Crohn's disease. Risankizumab is being investigated for atopic dermatitis.

Indications:

This drug is primarily indicated for: Risankizumab is indicated to treat: - moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. - active psoriatic arthritis in adults. In Canada and Europe, it may be used alone or in combination with a conventional non-biologic disease-modifying antirheumatic drug (cDMARD) (e.g, methotrexate). - moderately to severely active Crohn's disease in adults. In Canada, it is used in patients who have had an inadequate response, intolerance, or demonstrated dependence on corticosteroids; or an inadequate response, intolerance, or loss of response to immunomodulators or biologic therapies. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Risankizumab undergoes metabolic processing primarily in: The metabolic pathway of risankizumab has not been fully characterized. As a humanized IgG1 monoclonal antibody, it is likely to be catabolized into small peptides and amino acids in the same way as endogenous IgG. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Risankizumab are crucial for its therapeutic efficacy: Drug plasma concentrations increased dose-proportionally after subcutaneous administration of a single dose over the dose range from 18 mg to 360 mg and intravenous administration over a dose range from 200 mg to 1800 mg via a 3-hour infusion. In patients with plaque psoriasis who received a subcutaneous dose of 150 mg risankizumab, steady-state peak concentration (C_max) and trough concentration (C_trough) were 12 mcg/mL and 2 mcg/mL, respectively. In subjects with Crohn’s disease treated with 600 mg intravenous induction dose at Weeks 0, 4, and 8, followed by 180 mg or 360 mg subcutaneous maintenance dose at Week 12 and every 8 weeks thereafter, the median Cmax and Ctrough are estimated to be 156 mcg/mL and 38.8 mcg/mL, respectively, during Weeks 8-12; and the steady state median Cmax and Ctrough are estimated to be 14.0 mcg/mL and 4.1 mcg/mL, respectively for 180 mg or 28.0 mcg/mL and 8.1 mcg/mL, respectively, for 360 mg, during Weeks 40-48. The absolute bioavailability of risankizumab was approximately 74 to 89% following subcutaneous injection. In healthy subjects, following administration of a single subcutaneous dose, C_max was reached by 3 to 14 days. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Risankizumab is an important consideration for its dosing schedule: The terminal elimination half-life was approximately 28 days in patients with plaque psoriasis and 21 days in patients with Crohn’s disease. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Risankizumab exhibits a strong affinity for binding with plasma proteins: No information is available. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Risankizumab from the body primarily occurs through: As an IgG1 monoclonal antibody, risankizumab is not expected to be filtered by glomerular filtration in the kidneys or to be excreted as an intact molecule in the urine. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Risankizumab is distributed throughout the body with a volume of distribution of: The estimated steady-state volume of distribution (inter-subject CV%) was 11.2 L (34%) in subjects with plaque psoriasis, and 7.68 L (64%) in subjects with Crohn’s disease. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Risankizumab is a critical factor in determining its safe and effective dosage: The estimated systemic clearance (inter-subject CV%) was 0.31 L/day (24%) in patients with plaque psoriasis and 0.30 L/day (34%) in patients with Crohn’s disease. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Risankizumab exerts its therapeutic effects through: Risankizumab works to suppress the inflammatory effects of interleukin (IL)-23. It inhibits the release of pro-inflammatory cytokines and chemokines. _In vitro_, risankizumab blocked IL-17 production; however, risankizumab does not actually bind to IL-17. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Risankizumab functions by: Interleukin (IL)-23 is a pro-inflammatory cytokine implicated in various chronic inflammatory disorders, such as plaque psoriasis, psoriatic arthritis, and Crohn's disease. IL-23 binds to the IL-23 receptor to activate the IL-23/Th17 axis, which is responsible for mediating T cell-mediated immune responses and inflammation. The IL-23/Th17 axis triggers the differentiation of Th-17 and Th-22 cells and induces the release of inflammatory cytokines and chemokines such as IL-17. While the IL-23/Th17 axis serves a critical role in protection against pathogens, it is also involved in chronic, autoimmune, inflammatory disorders. IL-23 is made up of two subunits, p19 and p40: p19 is specific to IL-23 and p40 is present on both IL-12 and IL-23. Risankizumab binds to the p19 subunit of IL-23 with high affinity and neutralizes it, thereby preventing its interaction with the IL-23 receptor and activation of IL-23 signalling cascades. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Risankizumab 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:

Risankizumab is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Antibodies, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antineoplastic and Immunomodulating Agents, Blood Proteins, Globulins, Immunoglobulins, Immunoproteins, Immunosuppressive Agents, Immunotherapy, Interleukin Inhibitors, Interleukin-23 Antagonist, Interleukin-23 Subunit p19, Misc. Skin and Mucous Membrane Agents, Proteins, Selective Immunosuppressants, 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 Risankizumab include:

• Molecular Weight: 149000.0
• Molecular Formula: C6476H9992N1720O2016S44