Vedolizumab is a humanizedIgG1monoclonal antibody that targets theα4β7integrinfor the treatment of ulcerative colitis and Crohn's disease.

Integrin^[1]

Vedolizumab does not bind to the majority of memory CD4+ T lymphocytes (60%), neutrophils, and most monocytes. The highest level of vedolizumab binding is to a subset (25%) of human peripheral blood memory CD4+ T lymphocytes that include gut-homing interleukin 17 T-helper lymphocytes. Vedolizumab also binds to eosinophils at high levels, and to naive T-helper lymphocytes, naive and memory cytotoxic T lymphocytes, B lymphocytes, natural killer cells, and basophils at lower levels; vedolizumab binds to memory CD4+ T and B lymphocytes with subnanomolar potency (EC₅₀=0.3-0.4 nM). Vedolizumab selectively inhibits adhesion of α4β7-expressing cells to mucosal addressin cell adhesion molecule 1 (IC₅₀=0.02-0.06 μg/mL) and fibronectin (IC₅₀=0.02 μg/mL), but not vascular cell adhesion molecule 1^[1].

Blockade of α4β7 receptors on T-lymphocytes has been shown to occur for several weeks after a single dose of vedolizumab. The drug concentration following the infusion has been shown to be dose related with a mean maximum concentration of 12.5 μg/mL in those receiving 0.5 mg/kg of vedolizumab and 52.0 μg/mL in those receiving 2 mg/kg. The serum half-life of these two doses is 9-12 days respectively and saturation of α4β7 receptors on T-lymphocytes is >90% at both 4-6 weeks following infusion. In a dose ranging study, the serum drug concentrations increase with increasing dose and when regular induction infusions are used (on day 1, 15, 29 and 85), the serum half-life is between 15 and 22 days across all groups^[1].

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