Финголимод

Description

Fingolimod is a first-in-class oral sphingosine-1-phosphate (S1P) receptor modulator approved by regulators as an antineoplastic and immunomodulatory agent (ATC code L04AA27) for the treatment of relapsing forms of multiple sclerosis. In the body, the substance is rapidly phosphorylated, and the resulting fingolimod phosphate acts as a “super-agonist” of the S1P1 receptor on the surface of thymocytes and lymphocytes, causing internalization and degradation of this receptor. As a result, cells stop responding to the S1P1 signal, which is necessary for the release of lymphocytes from lymph nodes and secondary lymphoid tissues: the number of B and T lymphocytes in the intravascular bed and their recirculation to extravascular compartments, including the central nervous system, decreases. In clinical trials, the 0.5 mg dose reduced the relapse rate by 48–54% relative to placebo and the risk of progression of disability by 17–30% over two years of follow-up.

Basic Attributes

• CAS No: 162359-55-9
• Chemical formula: C19H33NO2
• Molecular weight: 307.478; exact weight: 307.47
• UNII: 3QN8BYN5QF
• DSSTox ID: DTXSID40167363
• NCI Thesaurus Code: C74202
• ATC code: L04AA27 - L: antitumor and immunomodulatory agents
• PSA specifications: 66.5
• XLogP3: 4.2

Physico-chemical characteristics

• Density: 1.0±0.1 g/cm3
• Melting point: 121–124 °C
• Boiling point: 479.498 °C
• Flash point: 243.8±28.7°C
• Refractive index: 1.531
• Solubility in water: soluble
• Dissociation constant: pKa 8

Scope of application

An oral drug for the treatment of relapsing forms of multiple sclerosis in adults, and has also been studied in children under separate clinical programs. The mechanism of action is based on the retention of lymphocytes in lymphoid tissue, which reduces their influx into the central nervous system and autoimmune damage to myelin.

Observation during therapy

Since modulation of S1P receptors affects lymphocytes, as well as cells of the cardiovascular system and retina, the initiation of fingolimod therapy is accompanied by medical monitoring of heart rate and conductivity in the first hours after taking the first dose, and during treatment - periodic monitoring of ophthalmological status (risk of macular edema) and liver function indicators. Discontinuation of the drug requires a gradual restoration of the immune status due to the long-term effect of lymphocyte sequestration and increased susceptibility to infections during this transition period.

Storage and transportation

Store in original, tightly closed container, in a dry place at room temperature, away from direct sunlight. As a medicinal product, fingolimod is available with a prescription and requires compliance with requirements for the storage and circulation of medicinal products; There is no specific UN transport code for the substance.