Department of Pediatrics, Columbia University, New York, NY, USA.
Bone Marrow Transplant. 2013 Jan;48(1):19-25. doi: 10.1038/bmt.2012.105. Epub 2012 Jun 11.
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) i.v. BU administration in pediatric allo-SCT recipients is limited. We prospectively examined the PK results in a cohort of pediatric allo-SCT recipients receiving i.v. 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 (CI₉₅): 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 CI₉₅ 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 i.v. BU q6 h PK seen in the literature, and in pediatric allo-SCT recipients, is a feasible, attractive alternative to i.v. q6h dosing.
静脉注射 BU 每日四次（q6h）已被证明在儿科 allo-SCT 受者中是安全有效的。虽然更频繁的给药是理想的，但在儿科 allo-SCT 受者中，每日两次（q12h）静脉注射 BU 的药代动力学（PK）数据有限。我们前瞻性地检查了接受 allo-SCT 前作为预处理的一部分接受每日两次静脉注射 BU（q12h）的儿科 allo-SCT 受者队列中的 PK 结果。在第一次预处理剂量后获得 BU 水平。PK 参数分析（n=49）得出以下 95%置信区间（CI₉₅）：体重归一化分布容积：0.65-0.73 L/kg；半衰期（t(1/2)）：122-147 min；体重归一化清除率（CL(n)）：3.4-4.3 mL/min/kg；和曲线下面积：1835-2180 mmol × min/L。根据这些结果，计算出稳态浓度的 CI₉₅在 628-746 ng/mL 之间。≤4 岁和>4 岁受者之间的比较显示 t(1/2)（平均值：115 与 146 min，P=0.008）和 CL(n)（平均值：4.4 与 3.5 mL/min/kg，P=0.038）有显著差异。静脉注射 BU q12h 的 PK 与文献中静脉注射 BU q6h PK 相当，在儿科 allo-SCT 受者中，是静脉注射 q6h 给药的可行且有吸引力的替代方案。
