Accurate targeting of daily intravenous busulfan with 8-hour blood sampling in hospitalized adult hematopoietic cell transplant recipients.
Accurate targeting of daily intravenous busulfan with 8-hour blood sampling in hospitalized adult hematopoietic cell transplant recipients.
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通过 8 小时血液采样对住院成人造血细胞移植受者进行每日静脉注射白消安的准确靶向。
DOI：
10.1016/j.bbmt.2011.06.013
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
McCune,JeannineS
中科院分区：
文献类型：
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作者：
Yeh,RosaF;Pawlikowski,MatthewA;Blough,DavidK;McDonald,GeorgeB;O'Donnell,PaulV;Rezvani,Andrew;Deeg,HJoachim;McCune,JeannineS
每日静脉注射 (i.v.) 白消安越来越多地用于造血细胞移植 (HCT) 预处理方案。使用治疗药物监测 (TDM)，可以以每 6 小时一次的传统频率将静脉注射白消安剂量定向 (TBu) 至患者特定的稳态浓度 (Css)。在本报告中，我们描述了每日静脉注射 TDM 的经验。在成人人群中进行白消安的研究，具体目标是 (1) 评估与白消安清除率相关的协变量，以及 (2) 评估 TDM 门诊每日 TBu 给药的可行性，并在 6 小时内进行药代动力学采样。对 87 名成人进行回顾性药代动力学分析，该成人每天接受 TBu 作为环磷酰胺的一部分，然后接受 TBU (CY/TBU)、单磷酸氟达拉滨 (氟达拉滨)，然后接受 TBU，或同时接受 TBU 和氟达拉滨调理。 85% 每天接受静脉注射的患者达到了预期的 Css。白消安。白消安清除率与性别或年龄无关，但与给药日期和调理方案相关 (P = .0016)。在接受 CY/TBU 的患者中，在给药日之间未发现清除率存在差异 (P > .36)；然而，接受氟达拉滨治疗方案的患者的清除率显着下降 (P = .0016)。白消安清除率和 8、11 或 24 小时药代动力学采样的 Cs 估计值具有可比性 (P > .4)。然而，6 小时内个体患者浓度-时间数据的药代动力学模型无法可靠地估计白消安清除率或 Css。
Daily intravenous (i.v.) busulfan is increasingly being used in hematopoietic cell transplantation (HCT) conditioning regimens. Intravenous busulfan doses administered at the traditional frequency of every 6 hours can be targeted (TBu) to a patient-specific concentration at steady state (Css) using therapeutic drug monitoring (TDM). In this report, we describe our experiences with TDM of daily i.v. busulfan in an adult population, with the specific aims of (1) evaluating covariates associated with busulfan clearance, and (2) assessing the feasibility of TDM for outpatient administration of dailyTBu with pharmacokinetic sampling over 6 hours. A retrospective pharmacokinetic analysis was conducted in 87 adults receiving dailyTBu as part of cyclophosphamide followed byTBU (CY/TBU), fludarabine monophosphate (fludarabine) followed byTBU, orTBU concurrent with fludarabine conditioning. The desired Csswas achieved in 85% of patients receiving daily i.v. busulfan. Busulfan clearance was not associated with sex or age, but was associated with the day of dosing and conditioning regimen (P = .0016). In patients receiving CY/TBU, no differences in clearance were found between dosing days (P > .36); however, clearance decreased significantly in patients receiving fludarabine-based regimens (P = .0016). Busulfan clearance and Cssestimates from pharmacokinetic sampling over 8, 11, or 24 hours were comparable (P > .4). However, pharmacokinetic modeling of individual patient concentration-time data over 6 hours could not reliably estimate busulfan clearance or Css.