US Naval Academy, Annapolis, MD, 21402, USA,
J Cancer Res Clin Oncol. 2013 Dec;139(12):2035-45. doi: 10.1007/s00432-013-1508-z. Epub 2013 Sep 27.
Objective of this work was to extend pharmacokinetic scaling theory of the writer for bolus dosing to include the case of constant-rate i.v. dosing over fixed interval so as to allow projection of adult dose and schedule of typically administered anticancer agents to children.
The basis for the scaling is the requirement of time-scaled likeness of the plasma concentrations of an agent for adult and child. Algebraic expressions are established for describing the time history of the concentrations, and formulas for dose and dosing interval are determined so as to ensure the requirement on concentrations.
Scaling results for simple drug behavior are illustrated using clinical data for the anticancer agent carboplatin. Basic aspects of the theory are confirmed for dose and dosing interval of adult and 4-year-old child. The theory is also shown to describe tolerable doses for children when scaled from adult dosing requirements and to have application in determining dosing conditions for children requiring individualized dosing because of renal impairment. Scaling with more complex drug behavior is illustrated using preclinical and clinical data for the anticancer agent docetaxel. Adult-to-child scaling is demonstrated and shown to be consistent with previously reported clinical data. Additional consideration is given to the anticancer agents etoposide and melphalan, as widely used in pediatric chemotherapy, and also to the modern practice of combination chemotherapy.
Basic theory for scaling adult dose and schedule of anticancer agents to children is presented and demonstrated to be plausible in providing insight into existing and proposed pediatric treatment protocols.
本工作的目的是将作者的单次给药药代动力学比例化理论扩展到包括固定间隔恒速静脉滴注的情况，以便能够将典型的抗癌药物的成人剂量和方案预测到儿童。
比例化的基础是要求成人和儿童的药物血浆浓度具有时间比例相似性。建立了描述浓度随时间变化的代数表达式，并确定了剂量和给药间隔的公式，以确保满足浓度要求。
使用抗癌药物卡铂的临床数据说明了简单药物行为的比例化结果。确认了成人和 4 岁儿童的剂量和给药间隔的理论基本方面。该理论还表明，当从成人给药要求进行比例化并应用于因肾功能损害而需要个体化给药的儿童的给药条件时，可以描述儿童可耐受的剂量。使用抗癌药物多西紫杉醇的临床前和临床数据说明了更复杂药物行为的比例化。进行了成人到儿童的比例化，并与先前报道的临床数据一致。还考虑了广泛用于儿科化疗的抗癌药物依托泊苷和苯丙氨酸，以及现代联合化疗的实践。
提出了将抗癌药物的成人剂量和方案比例化到儿童的基本理论，并证明其在为现有和拟议的儿科治疗方案提供深入了解方面是合理的。
