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General Description:

Tildrakizumab, identified by CAS number 1326244-10-3, is a notable compound with significant therapeutic applications. Tildrakizumab is a high-affinity, humanized, IgG1 κ antibody targeting interleukin 23 p19 that shows promise in the evolution of treatment strategy in chronic plaque psoriasis . The Food and Drug Administration (FDA) approved ILUMYA (tildrakizumab-asmn) for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy in March 2018. The approved recommended dosage of ILUMYA is a subcutaneous injection of 100 mg at Weeks 0, 4, and every 12 weeks thereafter . A study was performed on the pharmacokinetics of this drug on various ethnicities. The pharmacokinetics of tildrakizumab were similar in Japanese, Caucasian, and Chinese subjects .

Indications:

This drug is primarily indicated for: Moderate-severe plaque psoriasis , . Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Tildrakizumab undergoes metabolic processing primarily in: The metabolic pathway of tildrakizumab has not been characterized. As a humanized IgG1/k monoclonal antibody, tildrakizumab is expected to be degraded into small peptides and amino acids via catabolic pathways in a manner similar to endogenous IgG . The AUCinf of dextromethorphan (CYP2D6 substrate) increased by 20% when used concomitantly with tildrakizumab 200 mg (two times the approved recommended dose) administered subcutaneously at Weeks 0 and 4 in subjects with plaque psoriasis. No clinically significant changes in AUCinf of caffeine (CYP1A2 substrate), warfarin (CYP2C9 substrate), omeprazole (CYP2C19 substrate), and midazolam (CYP3A4 substrate) were observed . This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Tildrakizumab are crucial for its therapeutic efficacy: The mean (± SD) steady-state trough concentrations at 16 weeks post initiation of treatment ranged from 1.22 ± 0.94 mcg/mL to 1.47 ± 1.12 mcg/mL. The geometric mean (CV%) steady-state Cmax was 8.1 mcg/mL (34%) . The absolute bioavailability of tildrakizumab is estimated to be about 73-80% after subcutaneous administration. The peak concentration (Cmax) is reached by approximately 6 days . The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Tildrakizumab is an important consideration for its dosing schedule: The half-life is approximately 23 days (23%) . This determines the duration of action and helps in formulating effective dosing regimens.

Volume of Distribution:

Tildrakizumab is distributed throughout the body with a volume of distribution of: The geometric mean (CV%) volume of distribution is 10.8 L (24%) . This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Tildrakizumab is a critical factor in determining its safe and effective dosage: The mean (CV%) systemic clearance is 0.32 L/day (38%) . It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Tildrakizumab exerts its therapeutic effects through: Tildrakuzimab is a targeted immunomodulator that decreases inflammation by inhibiting the action of various cytokines associated with plaque psoriasis, thus relieving its symptom of scaly plaques , . The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Tildrakizumab functions by: This drug selectively binds interleukin (IL)-23 p19 subunit of cytokine IL-23 and neutralizes its function IL-23 regulates Th17 cells and is a powerful activator of keratinocyte proliferation . Targeting IL-23p19 alone has been found to be a promising treatment approach in patients with moderate-to-severe chronic plaque psoriasis. Upon administration, downregulation of Th17 and Th22 cell responses occur . IL-23 is a naturally occurring cytokine that is involved in inflammatory and immune responses. Tildrakizumab inhibits the release of proinflammatory cytokines and chemokines . This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Tildrakizumab 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:

Tildrakizumab 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, Interleukin Inhibitors, Interleukin-23 Antagonist, Interleukin-23 Subunit p19, 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 Tildrakizumab include:

• Molecular Weight: 144400.0
• Molecular Formula: C6426H9918N1698O2000S46