Busulfan pharmacokinetics in adults – a real-world evaluation of intra-individual variability and the impact of obesity and deferasirox

Abstract

To avoid under- or overexposure caused by a high variability of busulfan’s pharmacokinetic parameters, therapeutic drug monitoring (TDM) is highly recommended. Nevertheless, it is not widely used in European transplant centers. We retrospectively analyzed real-world busulfan TDM data in adults in our center between 9/2016 and 11/2024 with special focus on overweight/obesity and comedication with deferasirox. Overall, 287 patients (161 male/126 female), median age 59.6 years (19.4–77.7), were included. Median calculated AUC after the first TDM was 17.1 mg*h/L with high interindividual variability (range: 9.6–37.9). Target attainment without TDM would only have been achieved in 59 patients (20.6%) using the standard dose, even if adjusted for overweight/obesity and comedication with deferasirox. Busulfan clearance (CL) was significantly reduced in patients receiving deferasirox (0.13 L/kgdosing weight [0.07–0.22] vs 0.20 [0.12–0.33], p < 0.001), while no influence of body weight was detectable. Overall, there were no Intra-individual changes in both CL (−0.65% [−41.72–57.79]) and Vd (−1.40% [−36.85–69.04) between doses. However, in one third of patients relevant deviations were observed, regardless of either body weight or comedication with deferasirox. In contrast to some published data, no general decrease in CL over time was observed.