In this article, we will discuss Plerixafor (Mechanism of Action). So, let’s get started.
Mechanism of Action
Plerixafor is an inhibitor of the CXCR4 chemokine receptor and blocks binding of its cognate ligand, stromal cell-derived factor-lq (SDF-1a). SDF-la and CXCR4 are recognized to playa role in the trafficking and homing of human hematopoietic stem cells (HSCs) to the marrow comparment. Once in the marrow, stem cell CXCR4 can act to help anchor these cells to the marrow matrix, either directly via SDF-1a or through the induction of other adhesion molecules. Treatment with p1erixafor resulted in leukocytosis and elevations in circulating hematopoietic progenitor cells in mice, dogs and humans. CD34+ cells mobilized by plerixafor were capable of engraftment with long-term repopulating capacity up to one year in canine transplantation models.
Pharmacodynamics
Data on the fold increase in peripheral blood CD34+ cell count (cells/mcL) by apheresis day were evaluated in two placebo-controlled clinical studies in patients with NHL and MM (Study 1 and Study 2, respectively). The fold increase in CD34+ cell count (cells/mcL) over the 24-hour period starting from the day prior to the first apheresis and ending the next mOffingjust before the first apheresis is summarized in Table 1. During
this 24-hour period, a single dose of Mozobil or placebo was administered 10 to 11 hours
prior to apheresis
Table 1: Fold Increase in Peripheral Blood CD34+ Cell Count Following Pretreatment with G-CSF and Administration of Plerixafor
• Study- Mozobil and G-CSF (Median/Mean (SD))- Placebo and G-CSF (Median/Mean (SD))
• Study 1- 5.0/6.1 (5.4)- 1.4/1.9 (1.5)
• Study 2- 4.8/6.4 (6.8)- 1.7/2.4(7.3)
In pharmacodynamic studies of Plerixafor in healthy volunteers, peak mobilization of
CD34+ cells was observed between 6 and 9 hours after administration. In pharmacodynamic studies of Plerixafor in conjunction with G-CSF in healthy volunteers, a sustained elevation in the peripheral blood CD34+ count was obsered from 4 to 18 hours after plerixafor administration with a peak CD34+ count between 10 and 14 hours.