Tralokinumab API Manufacturers

General Description:

Tralokinumab, identified by CAS number 1044515-88-9, is a notable compound with significant therapeutic applications. Atopic dermatitis (AD) is an inflammatory skin disorder that causes skin inflammation, skin barrier dysfunction, and chronic pruritus. It is estimated to affect up to 20% of adults and children worldwide, and is frequently associated with other atopic conditions such as asthma or allergic rhinitis. While AD is a heterogenous condition with a variety of apparent genetic and environmental causes, it is primarily driven by the pro-inflammatory cytokine interleukin-13 (IL-13). Tralokinumab is a fully human IgG4 monoclonal antibody targeted against IL-13. It neutralizes IL-13 activity by inhibiting its ability to bind with receptors, thus helping to alleviate AD symptoms. Tralokinumab was first approved for the treatment of atopic dermatitis by the EMA in June 2021, under the brand name Adtralza (Leo Pharma), and was subsequently approved in Canada in October 2021 and the US in December 2021.

Indications:

This drug is primarily indicated for: Tralokinumab is indicated in Canada, the US, and the EU for the treatment of moderate-to-severe atopic dermatitis in patients who are candidates for systemic therapy and are inadequately controlled with topical interventions. In Canada and US, tralokinumab is only approved for adults. In Europe, it is approved for use in patients 12 years of age and older. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Tralokinumab undergoes metabolic processing primarily in: As with other therapeutic and endogenous proteins, the metabolism of tralokinumab is likely to occur via catabolism to smaller peptides and amino acids and has not been studied directly. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Tralokinumab are crucial for its therapeutic efficacy: The absolute bioavailability of tralokinumab following subcutaneous administration is 76%, with a median T_max of 5-8 days. In clinical trials, steady-state serum concentrations were achieved by week 16 of treatment, with trough concentrations ranging from 98.0±41.1 mcg/mL to 101.4±42.7 mcg/mL. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Tralokinumab is an important consideration for its dosing schedule: The half-life of tralokinumab is approximately 22 days. This determines the duration of action and helps in formulating effective dosing regimens.

Route of Elimination:

The elimination of Tralokinumab from the body primarily occurs through: The elimination of tralokinumab occurs through a non-saturable proteolytic pathway. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Tralokinumab is distributed throughout the body with a volume of distribution of: The volume of distribution of tralokinumab as estimated by population pharmacokinetic analysis was 4.2 L. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Tralokinumab is a critical factor in determining its safe and effective dosage: The clearance of tralokinumab following subcutaneous administration was estimated to be 0.149 L/day. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Tralokinumab exerts its therapeutic effects through: Tralokinumab exerts its therapeutic effects by inhibiting the inflammatory cytokine (IL-13) primarily responsible for the pathogenesis of atopic dermatitis. It is administered subcutaneously with a loading dose of 600mg followed by a maintenance dose of 300mg every two weeks. In clinical studies, tralokinumab treatment decreased the concentrations of a number of Th2 and Th22 immunity biomarkers in the blood, including periostin, IL-22, serum IgE. It also reduced epidermal thickness and decreased the expression of Keratin 16 and Ki-67 in skin affected by atopic dermatitis. Hypersensitivity reactions, including anaphylaxis, have been reported following the use of tralokinumab. Patients experiencing a systemic hypersensitivity reaction should discontinue treatment and initiate immediate therapy as clinically indicated. Tralokinumab should not be used in patients with pre-existing helminth infections, as the influence of tralokinumab on the immune response against helminth infections is unclear. Patients with helminth infections should be treated prior to therapy with tralokinumab. Patients becoming infected during the course of therapy may be treated with anti-helminth medications, but should discontinue tralokinumab if the infection fails to resolve. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Tralokinumab functions by: Interleukin-13 (IL-13) is a pro-inflammatory cytokine that has been implicated as the primary driver of atopic dermatitis (AD). IL-13 binds with high affinity to both a heterodimeric form of IL-13Rα1 - complexed with IL-4Rα - and to IL-13Rα2, both of which are expressed on keratinocytes and fibroblasts. While IL-13Rα2 does not appear to act as a signal mediator, the binding of IL-13 to heterodimeric IL-4Rα and IL-13Rα1 activates downstream Janus kinase 2 (JAK2) and tyrosine kinase 2 (TYK2) pathways which proceed to activate various signal transducer and activator of transcription (STAT) pathways. STAT signalling induces the expression of periostin, an extracellular matrix protein which serves a number of physiological functions in addition to its pathogenic role in skin fibrosis and chronic allergic inflammation. IL-13 also appears to contribute to skin barrier dysfunction via an indirect downregulation of filaggrin (FLG), a structural protein essential for correct skin barrier functioning. Tralokinumab is a monoclonal antibody targeted against IL-13. It neutralizes the activity of IL-13 by blocking its interaction with both the IL-13Rα1/IL-4Rα receptor complex and IL-13Rα2 receptors. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Tralokinumab 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:

Tralokinumab is categorized under the following therapeutic classes: Agents for Dermatitis, Excluding Corticosteroids, Amino Acids, Peptides, and Proteins, Antibodies, Asthma, drug therapy, Blood Proteins, Dermatologicals, Globulins, Immunoglobulins, Immunoproteins, Interleukin-13 Antagonist, 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 Tralokinumab include:

• Molecular Weight: 147000.0
• Molecular Formula: C6374H9822N1698O2014S44