The pharmacokinetics and safety of twice daily i.v. BU during conditioning in pediatric allo-SCT recipients.
The pharmacokinetics and safety of twice daily i.v. BU during conditioning in pediatric allo-SCT recipients.
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每日两次静脉注射的药代动力学和安全性
DOI：
10.1038/bmt.2012.105
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发表时间：
2013
影响因子：
4.8
通讯作者：
Cairo,MS
中科院分区：
文献类型：
--
作者：
LeGall,JB;Milone,MC;Waxman,IM;Shaw,LM;Harrison,L;Duffy,D;vandeVen,C;Militano,O;Geyer,MB;Morris,E;Bhatia,M;Satwani,P;George,D;Garvin,JH;Bradley,MB;Schwartz,J;Baxter-Lowe,LA;Cairo,MS
静脉BU每日分四次（q6 h）已被证明是安全和有效的儿科allo-SCT受体。尽管希望降低给药频率，但在儿科allo-SCT受者中每日两次（q12 h）iv BU给药的药代动力学（PK）数据有限。我们前瞻性地检查了一组在allo-SCT前接受iv BU q12 h作为预处理的一部分的儿科allo-SCT受者的PK结果。BU水平在第一次剂量的预处理后获得。PK参数分析（n= 49）得出以下95%置信区间（CI 95）：体重标准化分布容积：0.65-0.73 L/kg; t1/2：122-147 min;体重标准化清除率（CL n）：3.4-4.3 mL/min/kg;曲线下面积：1835-2180 mmol× min/L。根据这些结果，计算稳态浓度，CI 95在628-746 ng/mL之间。年龄> 4岁与> 4岁受者之间的比较显示t1/2（平均值：115 vs 146 min，P= 0.008）和CL n（平均值：4.4 vs 3.5 mL/min/kg，P= 0.038）存在显著差异。在文献中观察到，静脉内BU q12 h的PK与静脉内BU q6 h的PK相当，在儿科allo-SCT接受者中，静脉内BU q12 h是静脉内q6 h给药的一种可行且有吸引力的替代方案。
Intravenous BU divided four times daily (q6 h) has been shown to be safe and effective in pediatric allo-SCT recipients. Though less frequent dosing is desirable, pharmacokinetic (PK) data on twice daily (q12 h) iv BU administration in pediatric allo-SCT recipients is limited. We prospectively examined the PK results in a cohort of pediatric allo-SCT recipients receiving iv BU q12 h as part of conditioning before allo-SCT. BU levels were obtained after the first dose of conditioning. PK parameter analysis (n= 49) yielded the following 95% confidence intervals (CI 95): weight-normalized volume of distribution: 0.65–0.73 L/kg; t 1/2: 122–147 min; weight-normalized clearance (CL n): 3.4–4.3 mL/min/kg; and area under the curve: 1835–2180 mmol× min/L. From these results, a steady state concentration was calculated with CI 95 between 628–746 ng/mL. Comparison between recipients⩽ 4 vs> 4 years old revealed significant differences in t 1/2 (mean: 115 vs 146 min, P= 0.008) and CL n (mean: 4.4 vs 3.5 mL/min/kg, P= 0.038). Intravenous BU q12 h had a comparable PK to iv BU q6 h PK seen in the literature, and in pediatric allo-SCT recipients, is a feasible, attractive alternative to iv q6h dosing.