Effect of age on the pharmacokinetics of busulfan in patients undergoing hematopoietic cell transplantation; an alliance study (CALGB 10503, 19808, and 100103).
Effect of age on the pharmacokinetics of busulfan in patients undergoing hematopoietic cell transplantation; an alliance study (CALGB 10503, 19808, and 100103).
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DOI：
10.1007/s00280-014-2571-0
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发表时间：
2014-11
影响因子：
3
通讯作者：
Egorin, Merrill J.
中科院分区：
文献类型：
--
作者：
Beumer, Jan H.;Owzar, Kouros;Lewis, Lionel D.;Jiang, Chen;Holleran, Julianne L.;Christner, Susan M.;Blum, William;Devine, Steven;Kolitz, Jonathan E.;Linker, Charles;Vij, Ravi;Alyea, Edwin P.;Larson, Richard A.;Ratain, Mark J.;Egorin, Merrill J.
由于非疾病相关的发病率和死亡率，患有急性髓性白血病（AML）和骨髓增生异常综合征（MDS）的老年患者经常被排除在含有白消安的清髓预处理方案之外。我们假设，与年轻患者相比，老年患者（> 60 岁）的白消安清除率 (BuCL) 会降低，这可能解释了观察到的白消安耐受性差异。三项 CALGB 造血细胞移植研究中的 AML 患者接受了静脉注射白消安的预处理方案治疗，剂量为 0.8 mg/kg。通过LC-MS测定血浆白消安浓度，并通过非房室方法进行分析。 BuCL 标准化为实际 (ABW)、理想 (IBW) 或校正 (CBW) 体重 (kg)。使用 Wilcoxon 秩和检验检查年龄组之间 BuCL 的差异。累计185名患者； 174 提供了可用的药代动力学数据。 29 名 ≥ 60 岁的患者（中位数 66；范围 60-74）的 BuCL 显着高于那些 <60 岁的患者（中位数 50；范围 18-60）：BuCL 236 vs 168 mL/min，p=0.0002； BuCL/ABW 3.0 与 2.1 mL/min/kg，p=0.0001； BuCL/IBW 3.8 vs 2.6 mL/min/kg，p=0.0035； BuCL/CBW 3.4 与 2.6 mL/min/kg，p=0.0005。两个年龄组的患者间清除率变异性 (CV%) 均高达 48%。苯妥英给药是一个潜在的混杂因素，无论体重正常化如何，都不影响 BuCL（p>0.34）。与我们的假设相反，在这些研究中，老年患者的 BuCL 显着高于年轻患者，并且不能解释先前报道的老年患者中观察到的白消安毒性增加。
Older patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) have often been excluded from myeloablative conditioning regimens containing busulfan because of non-disease related morbidity and mortality. We hypothesized that busulfan clearance (BuCL) in older patients (>60 years) would be reduced compared to that in younger patients, potentially explaining observed differences in busulfan tolerability. AML patients in three CALGB hematopoietic cell transplantation studies were treated with a conditioning regimen using IV busulfan, dosed at 0.8 mg/kg. Plasma busulfan concentrations were determined by LC-MS, and analyzed by non-compartmental methods. BuCL was normalized to actual (ABW), ideal (IBW) or corrected (CBW) body weight (kg). Differences in BuCL between age groups were examined using the Wilcoxon rank sum test. 185 patients were accrued; 174 provided useable pharmacokinetic data. Twenty-nine patients ≥ 60 years old (median 66; range 60–74) had a significantly higher BuCL vs those <60 years old (median 50; range 18–60): BuCL 236 vs 168 mL/min, p=0.0002; BuCL/ABW 3.0 vs 2.1 mL/min/kg, p=0.0001; BuCL/IBW 3.8 vs 2.6 mL/min/kg, p=0.0035; BuCL/CBW 3.4 vs 2.6 mL/min/kg, p=0.0005. Inter-patient variability in clearance (CV%) was up to 48% in both age groups. Phenytoin administration, a potential confounder, did not affect BuCL, regardless of weight normalization (p>0.34). Contrary to our hypothesis, BuCL was significantly higher in older patients compared to younger patients in these studies and does not explain the previously reported increase in busulfan toxicity observed in older patients.
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影响因子：
4.3
作者：
Alatrash, Gheath;de Lima, Marcos;Andersson, Borje S.
通讯作者：
Andersson, Borje S.
影响因子：
11.4
作者：
Cahn, JY;Labopin, M;Gorin, NC
通讯作者：
Gorin, NC
影响因子：
20.3
作者：
Kolitz, Jonathan E.;George, Stephen L.;Larson, Richard A.
通讯作者：
Larson, Richard A.
影响因子：
3.8
作者：
Kostrubsky, SE;Sinclair, JF;Mutlib, A
通讯作者：
Mutlib, A
DOI：
10.1053/bbmt.2002.v8.pm12374452
发表时间：
2002-01-01
影响因子：
4.3
作者：
Andersson, BS;Thall, PF;Champlin, RE
通讯作者：
Champlin, RE