Bridging Pharmacokinetics and Pharmacodynamics: A PBPK/PD Model-Based Approach for Deferasirox Dosing in Transfusion-Dependent Thalassemia.

ABSTRACT: Patients with transfusion-dependent thalassemia (TDT) require lifelong blood transfusions, resulting in excessive iron accumulation and necessitating effective chelation therapy. Deferasirox (DFX) is the primary oral iron chelator for managing iron overload; however, the response to this treatment varies substantially within different individuals, potentially because of differences in its pharmacokinetics (PK) and pharmacodynamics (PD). This study aimed to develop a physiologically based pharmacokinetic-pharmacodynamic (PBPK/PD) DFX model, integrating hepatic- and transfusion-derived iron burdens to assess their impact on DFX PK and optimize dosing. The model was developed using clinical PK data from Caucasian and Thai populations, comprising healthy individuals and patients with TDT. TDT-

SUBMITTER: Sakares W 

PROVIDER: S-EPMC12445128 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature