Evans W E, Sinkule J A, Crom W R, Dow L, Look A T, Rivera G
Cancer Chemother Pharmacol. 1982;7(2-3):147-50. doi: 10.1007/BF00254537.
The clinical pharmacokinetics of VM26 and VP16-213 were assessed in 15 children (median age 10 years) with acute leukemia, using a new high-performance liquid chromatography-electrochemical assay. Pharmacokinetic parameters were calculated by both model-dependent and compartment model-independent methods. These studies demonstrated substantial differences in the central volumes of distribution (VDc), steady-state volumes of distribution (VDss) and systemic clearances (Cls) of VM26 and VP16-213; with the VDc, VDss, and Cls all being smaller for VM26, Systemic clearances determined by model-independent methods were 5.2 +/- 1.0 ml/min/m2 (mean +/- SD) for VM26 and 17.8 +/- 11.2 ml/min/m2 for VP16-213. The major metabolites. detected in serum and urine were the hydroxy acids. Low levels of the picro-lactone isomers were detected in some patients while the aglycones were not detected in the serum or urine of any patients.
采用一种新的高效液相色谱 - 电化学分析法，对15名（中位年龄10岁）急性白血病患儿进行了VM26和VP16 - 213的临床药代动力学评估。通过模型依赖和非房室模型方法计算药代动力学参数。这些研究表明VM26和VP16 - 213的中央分布容积（VDc）、稳态分布容积（VDss）和全身清除率（Cls）存在显著差异；VM26的VDc、VDss和Cls均较小，通过非房室模型方法测定的全身清除率，VM26为5.2±1.0 ml/min/m²（平均值±标准差），VP16 - 213为17.8±11.2 ml/min/m²。在血清和尿液中检测到的主要代谢产物为羟基酸。在一些患者中检测到低水平的苦内酯异构体，而在任何患者的血清或尿液中均未检测到苷元。
