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18 BrownG
1 Introduction Busulfan, a bifunctional DNA-alkylating agent, is widely applied as a chemotherapeutic in combination with cyclophosphamide, cytarabine, and fludarabine before allogeneic hematopoietic cell transplantation (HCT) ( The clinical application of busulfan is complicated by its high inter- and intra-individual pharmacokinetics/pharmacodynamics (PK/PD) variability, particularly in children ( Furthermore, owing to its narrow therapeutic index and large PK/PD variability, administering an initial busulfan IV dose based only on body weight (WT) may result in failure to reach the target therapeutic window ( Model-informed precision dosing utilizes population PK (popPK) models combined with maximum posterior Bayesian estimation to optimize both initial and subsequent dosing regimens based on TDM measurements ( GST alpha 1 ( GSTA1 ) genetic variations, and dosing schedule (day/time) are the most well-documented factors contributing to busulfan clearance variability ( Body size descriptors, including body surface area (BSA), fat-free mass (FFM), and normal fat mass (NFM), significantly influence busulfan PK in pediatric patients ( mat ), and distribution volume (V) based on FFM ( Time-varying CL was observed over a 4-day treatment with an every-6-h dosing regimen of busulfan ( Genetic polymorphisms in GSTA1 are associated with 8%27% reduction in CL ( Given this intricate interplay of physiological and pharmacological factors, comprehensive understanding of busulfan PK characteristics becomes essential for target exposure attainment
Some individuals explore the wolverine stack to accelerate post-surgical recovery, though any such use should involve the surgical team and medical supervision
