Taha I A, Ahmad R A, Rogers D W, Pritchard J, Rogers H J
Cancer Chemother Pharmacol. 1983;10(3):212-6. doi: 10.1007/BF00255766.
The pharmacokinetics of high-dose IV melphalan (140 or 220 mg m-2) were studied after 12 administrations in 10 children (aged 2.5-16 years) undergoing chemotherapy for either neuroblastoma or Ewing's tumour. To assess whether a simpler and less expensive nitrobenzylpyridine (NBP) spectrophotometric assay for alkylating activity was a satisfactory alternative to high-pressure liquid chromatography (HPLC), the plasma melphalan concentration was estimated by both methods in five cases. Analysis of the disposition of melphalan gave a mean half-life of 1.3 +/- 1.0 (SD) h, clearance 18.4 +/- 9.4 l X h-1 X m-2, and apparent volume of distribution 26.3 +/- 18.0 l X m-2. These pharmacokinetic parameters were similar to those found in adults: no correlation was found between any parameter and age or glomerular filtration rate. NBP alkylating activity determinations yielded consistent results and good correlation with plasma melphalan concentration. However, concordance analysis indicated a consistent bias, the NBP assay always giving lower estimates of plasma melphalan concentration: HPLC assay therefore remains the method of choice for determining plasma melphalan pharmacokinetics.
对10名接受神经母细胞瘤或尤因氏肿瘤化疗的儿童（年龄在2.5至16岁之间）进行了12次大剂量静脉注射美法仑（140或220 mg m-2）后的药代动力学研究。为了评估一种更简单且成本更低的用于测定烷基化活性的硝基苄基吡啶（NBP）分光光度法是否是高压液相色谱法（HPLC）的令人满意的替代方法，在5例病例中用两种方法对血浆美法仑浓度进行了估算。美法仑处置分析得出平均半衰期为1.3±1.0（标准差）小时，清除率为18.4±9.4 l×h-1×m-2，表观分布容积为26.3±18.0 l×m-2。这些药代动力学参数与在成人中发现的参数相似：未发现任何参数与年龄或肾小球滤过率之间存在相关性。NBP烷基化活性测定产生了一致的结果，并且与血浆美法仑浓度具有良好的相关性。然而，一致性分析表明存在一致的偏差，NBP测定法总是给出较低的血浆美法仑浓度估计值：因此，HPLC测定法仍然是测定血浆美法仑药代动力学的首选方法。
