Indications
Lifitegrast is indicated for the treatment of the signs and symptoms associated with keratoconjunctivitis sicca, commonly known as dry eye syndrome. This condition is characterized by insufficient moisture on the eye's surface, leading to discomfort and potential damage if left untreated.
Pharmacodynamics
Lifitegrast operates as a lymphocyte function-associated antigen-1 (LFA-1) antagonist, providing therapeutic effects by disrupting the inflammatory cycle associated with dry eye syndrome. It achieves this by competitively inhibiting LFA-1, which consequently prevents T-cell recruitment, activation, and the release of proinflammatory cytokines. This mechanism of action not only alleviates the symptoms of dry eye but also mitigates damage to the ocular surface.
Absorption
Upon topical application, lifitegrast achieves a mean peak plasma concentration (Cmax) of 1.70 ng/mL within approximately 15 minutes, indicating rapid absorption. Quantifiable plasma concentrations have been observed to range from 0.55 ng/mL to 3.74 ng/mL. Notably, the drug's systemic exposure is limited, yet sufficient to produce significant clinical outcomes.
Metabolism
In vitro metabolism studies utilizing fresh human hepatocytes suggest that lifitegrast does not undergo significant metabolic processes. This minimal metabolism is advantageous as it reduces the potential for metabolic interactions with other drugs, thus simplifying its use in combination therapies.
Mechanism of Action
Lifitegrast functions by targeting and binding to the integrin, lymphocyte function-associated antigen-1 (LFA-1), located on the surface of leukocytes. This binding action inhibits the interaction between LFA-1 and its corresponding ligand, intercellular adhesion molecule-1 (ICAM-1), which is often overexpressed in the corneal and conjunctival tissues of patients with dry eye disease. The LFA-1/ICAM-1 interaction plays a crucial role in the formation of an immunological synapse, which subsequently leads to T-cell proliferation, activation, and migration to affected tissues. In vitro research has shown that lifitegrast can impede T-cell adhesion to ICAM-1 in a specific human T-cell line and can also suppress the secretion of inflammatory cytokines, mediators, chemokines, TNF-α, and IL-1 in human peripheral blood mononuclear cells.
