This study assessed the pharmacokinetic characteristics and the exposure-response relationship of radotinib, a second-generation tyrosine kinase inhibitor for chronic myeloid leukemia (CML). Newly diagnosed CML patients (n=24) received 300 mg of radotinib twice daily. Blood samples were collected on Days 1 and 14. Additional measurements of trough concentrations (Ctrough) and efficacy assessments of major molecular response (MMR) were conducted at Months 3, 6, 9 and 12, whereas adverse events were monitored throughout the study. On Day 1, the median values of maximum concentration (Cmax), time to Cmax (tmax) and area under the concentration-time curve over a dosing interval (AUCτ) were 0.49 μg/mL, 3.0 hours and 3.43 μg·h/mL, respectively. By Day 14, the median AUCτ increased to 11.98 μg·h/mL, which indicates substantial accumulation (median accumulation ratio, Rac, 3.59). The median half-life calculated from Rac was 25.5 hours suggesting the dosing interval to be lengthened. Ctrough was used as the surrogate of radotinib exposure, since a strong correlation (Spearman correlation, r=0.974) exists between Ctrough and AUCτ. The median value of Ctrough was significantly higher in patients with MMR than in those without MMR at Month 12 (1.58 versus 1.12 μg/mL, Mann-Whitney U test, p=0.037). Radotinib was well-tolerated with no significant exposure-safety relationship. The findings suggest that Ctrough may be used in dose adjustments for optimizing outcomes in CML patients.