Combarel David, Tran Julie, Delahousse Julia, Vassal Gilles, Paci Angelo
Service de Pharmacologie, Département de biologie et pathologie médicale, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
Université Paris-Saclay, Faculté de Pharmacie, Université Paris-Saclay, Chatenay-Malabry, France.
Expert Opin Drug Metab Toxicol. 2023 Feb;19(2):75-90. doi: 10.1080/17425255.2023.2192924. Epub 2023 Mar 29.
Busulfan is an alkylating agent widely used in the conditioning of hematopoietic stem cell transplantation possessing a complex metabolism and a large interindividual and intra-individual variability, especially in children. Combined with the strong rationale of busulfan PK/PD relationships, factors altering its clearance (e.g. weight, age, and GST-A genetic polymorphism mainly) can also affect clinical outcomes.
This review aims to provide an overview of the current knowledge on busulfan pharmacokinetics, its pharmacokinetics variabilities in pediatric populations, drug-drug interactions (DDI), and their consequences regarding dose individualization. This review was based on medical literature up until October 2021.
To ensure effective busulfan exposure in pediatrics, different weight-based nomograms have been established to determine busulfan dosage and provided improved results (65-80% of patients correctly exposed). In addition to nomograms, therapeutic drug monitoring (TDM) of busulfan measuring plasmatic concentrations to estimate busulfan pharmacokinetic parameters can be used. TDM is now widely carried out in routine practices and aims to ensure the targeting of the reported therapeutic windows by individualizing busulfan dosing based on the clearance estimations from a previous dose.
白消安是一种烷化剂，广泛用于造血干细胞移植的预处理，其代谢复杂，个体间和个体内差异较大，尤其是在儿童中。结合白消安药代动力学/药效学关系的有力理论依据，改变其清除率的因素（主要是体重、年龄和谷胱甘肽S-转移酶A基因多态性）也会影响临床结果。
本综述旨在概述目前关于白消安药代动力学、其在儿科人群中的药代动力学变异性、药物相互作用（DDI）以及它们对剂量个体化的影响的知识。本综述基于截至2021年10月的医学文献。
为确保儿科患者对白消安有有效的暴露，已建立了不同的基于体重的列线图来确定白消安剂量，并取得了更好的结果（65-80%的患者暴露正确）。除了列线图，还可以使用测量血浆浓度以估计白消安药代动力学参数的白消安治疗药物监测（TDM）。TDM目前在常规实践中广泛开展，旨在通过根据前一剂的清除率估计值对白消安剂量进行个体化，确保达到报告的治疗窗目标。
