Vincristine pharmacokinetics after repetitive dosing in children
Vincristine pharmacokinetics after repetitive dosing in children
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DOI：
10.1007/s002800050968
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发表时间：
1999-09-01
影响因子：
3
通讯作者：
de Graaf, SSN
中科院分区：
文献类型：
--
作者：
Gidding, CEM;Meeuwsen-de Boer, GJ;de Graaf, SSN
目的：我们研究32例急性淋巴细胞白血病、非霍奇金淋巴瘤或威尔姆斯肿瘤患儿在169周静脉注射长春新碱后的反应。该研究的目的是确定患者体内和患者间长春新碱处置的变异性以及影响这种变异性的人口统计学、临床和生化特征。方法：采用电化学检测的高效液相色谱法测定长春新碱血药浓度。采用了一种基于贝叶斯参数估计算法的有限采样策略，该算法是ADAPT II软件包的一部分。对数据拟合两室一阶模型，并利用ADAPT II软件根据模型计算药代动力学参数。统计分析采用方差分析（ANOVA）、t检验、简单回归和多元回归分析以及非参数或鲁棒等效分析。结果：在分布半衰期、消除半衰期、全身清除率、稳态表观分布容积、浓度-时间曲线下面积等方面，患者内部和患者间存在较大差异。除分布半衰期外，所有这些参数的患者内变异性显著小于患者间变异性。诊断或治疗方案被证明是最具预测性的特征；白血病和非霍奇金淋巴瘤患者的总清除率明显高于Wilms肿瘤患者。结论：我们得出结论，小儿癌症患者的长春新碱药代动力学的患者内和患者间变异性很大，这种变异性虽然受到诊断的显著影响，但在很大程度上仍然是不可预测的。
Purpose: We studied vincristine disposition after 169 weekly i.v. bolus injections in 32 children with acute lymphoblastic leukemia, non-Hodgkin lymphoma, or Wilms' tumor. The aim of the study was to determine intrapatient and interpatient variability in vincristine disposition and demographic, clinical, and biochemical characteristics influencing this variability. Methods: Vincristine plasma concentrations were measured by a high-performance liquid chromatography assay with electrochemical detection. A limited sampling strategy was used based on a bayesian parameter estimation algorithm that is part of the ADAPT II software package. A two-compartment, first-order model was fitted to the data, and pharmacokinetic parameters were calculated from the model using the ADAPT II software. For statistical analysis, analysis of variance (ANOVA), t test, simple and multiple regression analysis, and non-parametric or robust equivalents were used. Results: Results showed a large intrapatient and interpatient variability in distribution half-life, elimination half-life, total body clearance, apparent volume of distribution at steady state, and area under the concentration-time curve. Intrapatient variability was significantly smaller than interpatient variability for all these parameters except distribution half-life. The diagnosis or treatment protocol turned out to be the most predictive characteristic; leukemia and non-Hodgkin lymphoma patients had a significantly higher total body clearance than Wilms' tumor patients. Conclusions: We conclude that both intrapatient and interpatient variability in vincristine pharmacokinetics is large in pediatric cancer patients and that variability, although significantly influenced by diagnosis, largely remains unpredictable.