Population Pharmacokinetic Analysis of Busulfan in Japanese Pediatric and Adult HCT Patients

Busulfan is the most common chemotherapy agent used in allogeneic hematopoietic cell transplant (HCT) conditioning regimens. As narrow therapeutic index and interpatient variability exists in the effectiveness and toxicity of conditioning regimens, personalizing intravenous busulfan therapy is desirable. Population pharmacokinetic‐based approaches have been applied to therapeutic drug monitoring for the purpose of personalizing therapy. A population pharmacokinetic analysis with the objective of personalizing therapy in Japanese patients was conducted by integrating pediatric patient data with adult patient data. McCune's model, a 2‐compartment model that includes maturation of clearance and allometric scaling of clearance and volume of distribution, was used for the analysis. McCune's model could precisely describe the Japanese data, and the estimated parameters were similar to McCune's results for non‐Japanese, indicating that there are no racial differences in busulfan pharmacokinetics. Using this model, the plasma concentrations for once‐daily dosing were simulated to adapt new dosage regimens for the benefit and convenience of both patients and medical staff. The predicted busulfan concentrations were within the therapeutic range.