Two-point blood sampling is sufficient and necessary to estimate the area under the concentration-time curve for intravenous busulfan in infants and young children.
Two-point blood sampling is sufficient and necessary to estimate the area under the concentration-time curve for intravenous busulfan in infants and young children.
复制标题
两点采血足以估计婴儿和幼儿静脉注射白消安的浓度-时间曲线下面积。
DOI：
10.1002/pbc.29069
复制
发表时间：
2021
影响因子：
3.2
通讯作者：
Yamatani A.
中科院分区：
文献类型：
--
作者：
Utano T;Kato M;Sakamoto K;Osumi T;Matsumoto K;Tomizawa D;Matsumoto K;Yamatani A.
背景：治疗药物监测对预防干细胞移植不良事件和改善预后非常重要。我们研究了静脉注射布苏凡的药代动力学，并评估了有限采样策略（LSS）作为估计浓度-时间曲线下面积（AUC）的简单方法的实用性。该研究包括在2015年8月至2020年5月期间接受静脉注射丁硫芬的54名儿童的87次丁硫芬测量。从每个患者的3 - 5个采血点计算AUC，并计算开始布苏凡输注后1、2、3、4和6小时（分别为C1、C2、C3、C4和C6） AUC与血浆浓度（ng/mL）的相关性。结果采用单点抽样策略，所有患者的预测AUC均以C6为基础（r2= 0.789，精度为11.0%）。基于c6的预测AUC对于体重为50 ~ 23 kg的青少年患者是可以接受的（r2= 0.937，精度为5.9%），但对于体重≤23 kg的婴幼儿相关性较差（r2= 0.782，精度为11.4%）。通过两点抽样策略，基于c3和c6的预测AUC显示出最相关的浓度（r2= 0.943，精度为6.4%），即使在婴幼儿中也是如此，而基于c3和c6的预测AUC是可以接受的（r2= 0.963，精度为5.7%）。结论基于c6可预测青少年患者布苏凡的AUC。然而，在婴幼儿中，布苏凡的药代动力学存在显著的个体间差异，两点LSS对于准确预测AUC是必要的。
BackgroundTherapeutic drug monitoring for busulfan is important to prevent adverse events and improve outcomes in stem cell transplantation. We investigated intravenous busulfan pharmacokinetics and evaluated the utility of limited sampling strategy (LSS) as a simple method to estimate the area under the concentration‐time curve (AUC).ProcedureThe study comprised 87 busulfan measurements in 54 children who received intravenous busulfan between August 2015 and May 2020. AUCs were calculated from three to five blood sampling points in each patient, and the correlation between AUC and plasma concentrations (ng/mL) at 1, 2, 3, 4, and 6 h after initiating busulfan infusion (C1, C2, C3, C4, and C6, respectively).ResultsBy one‐point sampling strategy, the most relevant predicted AUC was based on C6(r2= 0.789; precision, 11.0%) in all patients. The predicted AUC based on C6was acceptable (r2= 0.937; precision, 5.9%) for adolescent patients weighing >23 kg, but the correlation was poor in infants and young children weighing ≤ 23 kg (r2= 0.782; precision, 11.4%). By two‐point sampling strategy, the predicted AUC based on C3and C6showed the most relevant concentrations (r2= 0.943; precision, 6.4%), even in infants and young children, whereas the predicted AUC based on C3and C6was acceptable (r2= 0.963; precision, 5.7%).ConclusionsThe AUC of busulfan can be predicted based on C6in adolescent patients. However, there was substantial interindividual variation in busulfan pharmacokinetics in infants and young children, in whom two‐point LSS was necessary for accurate AUC prediction.