Thirteen Years' Experience of Pharmacokinetic Monitoring and Dosing of Busulfan: Can the Strategy be Improved?
Thirteen Years' Experience of Pharmacokinetic Monitoring and Dosing of Busulfan: Can the Strategy be Improved?
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DOI：
10.1097/ftd.0b013e31829dc940
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发表时间：
2014-02-01
影响因子：
2.5
通讯作者：
Begg, Evan J.
中科院分区：
文献类型：
--
作者：
Buffery, Pamela J.;Allen, Kirstie M.;Begg, Evan J.
背景：自1998年以来，基督城医院一直提供白消安浓度监测和给药服务。本研究旨在观察（1）浓度时间曲线下面积（AUC）超出目标范围并进行剂量调整的患者百分比，（2）白消安清除率（CL）与体重的关系，以及（3）是否可以使用更少的样本来预测剂量。在口服给药后，通常在0.5、1、1.5和6小时，以及在开始2小时静脉内（IV）输注白消安后，在1、2、2.5、3、6、7、8、9、10、11、12、13、14、15、16、17、18、19、1和8小时。根据AUC与目标范围的比较进行剂量调整。IV组的CL和体重的关系用于制定修订的IV给药方案。使用较少的采样点估计的AUC的偏差和不精确性进行了检查，看看是否采样可以economized.Results：数据可用于150例患者，但6例患者，数据不完整，排除。在其余144例患者中（256个样本集，209例口服，47例IV，62%重复），38%（IV）和35%（口服）患者首次给药后AUC在目标范围内。分别有47%和34%的IV和口服给药患者进行了剂量调整，之后有更多患者达到目标AUC的趋势。CL与体重呈非线性关系。考虑到这一点，对初始IV给药方案进行了修订。在输注开始后的3个点（2.5，4，8小时）或2个点（2.5，8小时）进行白消安浓度测量的采样能够准确和精确地估计AUC（0-24）。37%的患者进行了剂量调整。CL与体重之间的关系用于修订初始IV给药方案。用于AUC估计的采样可减少至IV给药后的2个时间点。
Background: A busulfan concentration monitoring and dosing service has been provided by Christchurch Hospital since 1998. This study aimed to see (1) the percentage of patients with an area under the concentration time curve (AUC) outside the target range and had dose adjustment, (2) how busulfan clearance (CL) relates to body weight, and (3) if fewer samples could be used to predict doses.Methods: Blood samples were taken from patients after oral administration, usually at 0.5, 1, 1.5, and 6 hours, and after the start of a 2-hour intravenous (IV) infusion of busulfan, at 1, 2, 2.5, 3, 6, and 8 hours. Dose adjustment was made based on the AUC compared with the target range. The relationship of CL and body weight for the IV group was used to develop a revised IV dosing schedule. The bias and imprecision of AUCs estimated using fewer sampling points were examined to see if sampling could be economized.Results: Data were available for 150 patients but for 6 patients, data were incomplete and excluded. Of the remaining 144 patients (256 sample sets, 209 oral, 47 IV, 62% with repeats), 38% (IV) and 35% (oral) of patients had AUCs within the target range after the first dose. Dose adjustment was made in 47% and 34% of patients dosed IV and orally, respectively, after which there was a trend to more patients achieving the target AUC. A nonlinear relationship was found between CL and body weight. The initial IV dosing schedule was revised to take this into account. Sampling for busulfan concentration measurement at 3 points (2.5, 4, 8 hours) or 2 points (2.5, 8 hours) after the start of the infusion enabled accurate and precise estimates of AUC(0-24).Conclusions: Around two thirds of patients treated with busulfan were outside the target AUC range after the first dose. Dose adjustment was made in 37% of patients. The relationship between CL and body weight was used to revise the initial IV dosing schedule. Sampling for AUC estimation could be reduced to 2 time points after IV dosing.