Evaluation of Bruton's Tyrosine Kinase (BTK) inhibition with alternative doses of ibrutinib in subjects with Chronic Lymphocytic Leukemia (CLL).

ABSTRACT:

Purpose

To evaluate alternative ibrutinib dosing regimens that maintain Bruton's tyrosine kinase (BTK) receptor occupancy over the entire dosing interval for CLL patients using a model-based approach.

Methods

Ibrutinib inhibits B-cell proliferation via irreversible binding of BTK. As IC₅₀ is not an appropriate parameter to describe the potency of the inhibition in the presence of a covalent binding inhibitor. A BTK covalent binding model was developed using k_inact/K_I as key parameter to account for covalent binding. The ibrutinib-BTK covalent binding model was used to describe the effect of daily doses of 140, 280, 420 and 560 mg on the proportion of subjects with more than 90% BTK inhibition at steady state trough concentrations. Predictive

SUBMITTER: Ouerdani A 

PROVIDER: S-EPMC11870975 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature