Vincristine in childhood leukaemia:: no pharmacokinetic rationale for dose reduction in adolescents
Vincristine in childhood leukaemia:: no pharmacokinetic rationale for dose reduction in adolescents
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DOI：
10.1080/08035320310000000
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发表时间：
2003-01-01
期刊：
影响因子：
3.8
通讯作者：
de Graaf, SSN
中科院分区：
文献类型：
--
作者：
Frost, BM;Lönnerholm, G;de Graaf, SSN
目的：研究以相对较低剂量给予青少年长春新碱的常见做法是否有药代动力学依据。方法：共98例急性淋巴细胞白血病（ALL）患儿，年龄1.3-17.3岁，在诱导治疗的第一天进行研究。在注射长春新碱2.0 mg/m2（最大剂量2.0 mg）之前和之后10、30、360和1380 min采集血浆样品，并通过高效液相色谱法进行分析。结果如下：分布半衰期的中位数（和范围）为6.4 min（0.8-11.8），消除半衰期为1014 min（258-2570），分布容积为445 L/m2（137-1241），总清除率为362 ml/min/m2（134-2553）。未发现年龄与这些药代动力学参数之间存在相关性。浓度-时间曲线下面积（AUC）与年龄显著相关（p = 0.002; rho - 0.31），与长春新碱剂量的预期一致。体表面积>1 m2的儿童AUC较低，在8-9岁时达到，表明他们接受的治疗强度较低，因为长春新碱剂量上限为2.0 mg。结论：在该儿科人群中，长春新碱的药代动力学不具有年龄依赖性。因此，我们未发现青少年剂量降低的药代动力学依据。应仔细重新考虑将长春新碱剂量限制为2.0 mg的常见做法。
Aim: To investigate whether there is any pharmacokinetic rationale for the common practice of administering vincristine to adolescents at relatively lower doses than those to younger children. Methods: A total of 98 children, aged 1.3-17.3 y, with acute lymphoblastic leukaemia (ALL) were studied on day I of induction therapy. Plasma samples were drawn before and 10, 30, 360 and 1380 min after injection of vincristine 2.0 mg/m(2) (maximum dose 2.0 mg) and analysed by high-performance liquid chromatography. Results: The median value (and range) for distribution half-life was 6.4 min (0.8-11.8), elimination half-life 1014 min (258-2570), volume of distribution 445 L/m(2) (137-1241) and total body clearance 3 62 ml/min/m(2) (134-2553). No correlation was found between age and any of these pharmacokinetic parameters. The area under the concentration time curve (AUC) was significantly correlated to age (p = 0.002; rho - 0.31), as expected from the dosage of vincristine. The lower AUC in children with a body surface area >1 m(2), which is reached at 8-9 y of age, indicates that they received a less intense treatment because of the capping of the vincristine dose at 2.0 mg.Conclusions: Vincristine pharmacokinetics were not age dependent in this paediatric population. Thus, we found no pharmacokinetic rationale for dose reduction in adolescents. The common practice of limiting the vincristine dose to 2.0 mg should be carefully reconsidered.