Concentration-QTcF analysis of quizartinib in patients with newly diagnosed FLT3-internal-tandem-duplication-positive acute myeloid leukemia.

ABSTRACT: Quizartinib prolongs QT interval through inhibition of the slow delayed rectifier potassium current (I_Ks). We used non-linear mixed-effects modeling to explore the relationship between quizartinib and its pharmacologically active metabolite AC886 and the Fridericia-corrected QT interval (QTcF) in newly diagnosed acute myeloid leukemia (AML) patients. We evaluated linear and non-linear drug effect models, using triplicate QTcF measurements with available time-matched pharmacokinetic samples from the Phase 3 QuANTUM-First trial. The effect of intrinsic and extrinsic factors on model parameters was tested using stepwise covariate model building. Simulations were conducted to predict the change from baseline in QTcF (ΔQTcF) at the maximum concentration at steady-state (C_max,ss<

SUBMITTER: Vaddady P 

PROVIDER: S-EPMC11557512 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature