Gaffney Kelly J, Urban Theresa A, Lucena Mariana, Anwer Faiz, Dean Robert M, Gerds Aaron T, Hamilton Betty K, Jagadeesh Deepa, Kalaycio Matt E, Khouri Jack, Pohlman Brad, Sobecks Ronald, Winter Allison, Rybicki Lisa, Majhail Navneet S, Hill Brian T
2345Medical University of South Carolina, Charleston, SC, USA.
2569Cleveland Clinic, Cleveland, OH, USA.
J Oncol Pharm Pract. 2022 Jun 7:10781552221104422. doi: 10.1177/10781552221104422.
Busulfan-based conditioning regimens are associated with serious toxicities and literature reports increased risk of toxicities when daily area under the curve concentrations exceed 6000 µM-minute. We implemented real time pharmacokinetic-guided therapeutic drug monitoring of busulfan for myeloablative conditioning regimens. The objective was to compare toxicity of intravenous busulfan before and after therapeutic drug monitoring implementation. The primary endpoint was incidence of hepatotoxicity. Medical records were retrospectively reviewed with weight-based dose Busulfan/Cyclophosphamide (BuCy) conditioning from August 2017 through March 2018 ( = 14) and therapeutic drug monitoring from April 2018 through December 2018 ( = 22). Recipients of busulfan therapeutic drug monitoring were younger than those receiving weight-based dose (median: 45 vs. 58 years, = 0.008). No other baseline differences were observed. There was no difference in hepatotoxicity between therapeutic drug monitoring and weight-based dose (median 1 vs. 0 days, = 0.40). In the therapeutic drug monitoring group, 45% of patients had increases and 41% had decreases in busulfan dose after Bu1. Repeat pharmacokinetic after Bu2 were required in 32% of patients. A pharmacokinetic dose monitoring program for myeloablative conditioning intravenous busulfan regimens may be considered a safe practice in stem cell transplant recipients. The majority of patients receiving pharmacokinetic-guided therapeutic drug monitoring required dose changes and therapeutic drug monitoring patients had no significant difference in toxicity compared to those receiving weight-based dose.
基于白消安的预处理方案与严重毒性相关，文献报道当曲线下面积每日浓度超过6000 µM-分钟时，毒性风险会增加。我们对用于清髓性预处理方案的白消安实施了实时药代动力学指导的治疗药物监测。目的是比较治疗药物监测实施前后静脉注射白消安的毒性。主要终点是肝毒性的发生率。回顾性分析了2017年8月至2018年3月采用基于体重剂量的白消安/环磷酰胺（BuCy）预处理的医疗记录（n = 14）以及2018年4月至2018年12月采用治疗药物监测的医疗记录（n = 22）。接受白消安治疗药物监测的患者比接受基于体重剂量的患者更年轻（中位数：45岁对58岁，P = 0.008）。未观察到其他基线差异。治疗药物监测组和基于体重剂量组之间的肝毒性无差异（中位数1天对0天，P = 0.40）。在治疗药物监测组中，45%的患者在Bu1后白消安剂量增加，41%的患者剂量减少。32%的患者在Bu2后需要重复药代动力学检测。对于清髓性预处理静脉注射白消安方案，药代动力学剂量监测程序可被视为干细胞移植受者的一种安全做法。大多数接受药代动力学指导治疗药物监测的患者需要调整剂量，与接受基于体重剂量的患者相比，治疗药物监测组患者的毒性无显著差异。
