Sorafenib Dose Recommendation in Acute Myeloid Leukemia Based on Exposure-FLT3 Relationship.

ABSTRACT: Sorafenib administered at the approved dose continuously is not tolerated long-term in patients with acute myeloid leukemia (AML). The purpose of this study was to optimize the dosing regimen by characterizing the sorafenib exposure-response relationship in patients with AML. A one-compartment model with a transit absorption compartment and enterohepatic recirculation described the exposure. The relationship between sorafenib exposure and target modulation of kinase targets (FMS-like tyrosine kinase 3 (FLT3)-ITD and extracellular signal-regulated kinase (ERK)) were described by an inhibitory maximum effect (E_max ) model. Sorafenib could inhibit FLT3-ITD activity by 100% with an IC₅₀ of 69.3 ng/mL and ERK activity by 84% with an IC₅₀ of 85.7 ng/mL (both adju

SUBMITTER: Liu T 

PROVIDER: S-EPMC6039208 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature