Clinical pharmacokinetic characteristics and the food effect of radotinib

Abstract

Radotinib is a second-generation tyrosine kinase inhibitor that selectively targets BCR-ABL1 and is used for the treatment of chronic myeloid leukemia (CML). This study aimed to evaluate the clinical pharmacokinetic characteristics and the food effect of radotinib. Healthy volunteers received a single oral dose of radotinib 400 mg under fasted or fed conditions in a crossover manner, and CML patients received repeated oral doses of 300 mg twice daily. The pharmacokinetic characteristics were evaluated by a noncompartmental method, using plasma concentration-time data following a single administration in healthy volunteers, and on Days 1 and 14 in CML patients. The food effect was assessed by comparing the pharmacokinetic parameters under fed and fasted conditions in healthy volunteers. The pharmacokinetic analyses of radotinib included data from 23 healthy male volunteers and 24 patients newly diagnosed with CML. In both populations, the plasma concentrations of radotinib peaked at approximately 3 h. In healthy volunteers, the concentrations declined biexponentially with the terminal half-life (t1/2) of 17.5 h under fasted conditions. In CML patients, radotinib was substantially accumulated with the accumulation ratio of 3.59 on Day 14. The effective t1/2 derived from the accumulation ratio was 25.5 h. The systemic exposure to radotinib increased by 3.49-fold when administered after food intake, with time to maximum concentration delayed by 3 h. The results of the study provide essential pharmacokinetic information for the clinical use of radotinib in the treatment of CML patients. ClinicalTrials.gov, Identifier NCT06461078, NCT03722420.