Frost B M, Lönnerholm G, Koopmans P, Abrahamsson J, Behrendtz M, Castor A, Forestier E, Uges D R A, de Graaf S S N
Department of Women's and Children's Health, University Children's Hospital, Uppsala, Sweden.
Acta Paediatr. 2003 May;92(5):551-7.
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.
A total of 98 children, aged 1.3-17.3 y, with acute lymphoblastic leukaemia (ALL) were studied on day 1 of induction therapy. Plasma samples were drawn before and 10, 30, 360 and 1380 min after injection of vincristine 2.0 mg/m2 (maximum dose 2.0 mg) and analysed by high-performance liquid chromatography.
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/m2 (137-1241) and total body clearance 362 ml/min/m2 (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; p - 0.31), as expected from the dosage of vincristine. The lower AUC in children with a body surface area > 1 m2, 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.
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.
探讨对于青少年使用长春新碱的剂量相对低于年幼儿童这一普遍做法是否存在药代动力学依据。
在诱导治疗第1天，对98例年龄为1.3 - 17.3岁的急性淋巴细胞白血病（ALL）患儿进行研究。静脉注射长春新碱2.0 mg/m²（最大剂量2.0 mg）前及注射后10、30、360和1380分钟采集血浆样本，采用高效液相色谱法进行分析。
分布半衰期的中位数（及范围）为6.4分钟（0.8 - 11.8），消除半衰期为1014分钟（258 - 2570），分布容积为445 L/m²（137 - 1241），全身清除率为362 ml/min/m²（134 - 2553）。未发现年龄与这些药代动力学参数中的任何一项存在相关性。浓度 - 时间曲线下面积（AUC）与年龄显著相关（p = 0.002；r = 0.31），这与长春新碱的给药剂量预期一致。8 - 9岁时体表面积>1 m²的儿童AUC较低，表明由于长春新碱剂量上限为2.0 mg，他们接受的治疗强度较低。
在该儿科人群中，长春新碱的药代动力学不依赖于年龄。因此，我们未发现青少年降低剂量的药代动力学依据。应仔细重新考虑将长春新碱剂量限制在2.0 mg的普遍做法。
