Crom W R
Pharmaceutical Department, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Environ Health Perspect. 1994 Dec;102 Suppl 11(Suppl 11):111-7. doi: 10.1289/ehp.94102s11111.
Pharmacokinetic studies have made many significant contributions to rational therapeutics in children. Pharmacokinetic data have helped distinguish between differences in drug disposition and drug sensitivity in children as compared to adults and led to the establishment of age-specific dosage guidelines. Factors influencing the observed differences between drug disposition in children and adults are reviewed. Specific examples utilizing anticancer drugs are presented. The use of model substrates to study hepatic drug metabolism and renal excretion in children is described and some results are discussed. The significance of genetic polymorphic drug metabolism is presented and the use of model substrates to determine individual metabolic phenotypes is described. The use of pharmacokinetic data to define the maximum-tolerated systemic exposure rather than the maximum-tolerated dosage of anticancer drugs in children is presented.
药代动力学研究为儿童合理治疗做出了许多重大贡献。与成人相比，药代动力学数据有助于区分儿童药物处置和药物敏感性的差异，并促成了针对特定年龄的剂量指南的建立。本文综述了影响儿童与成人药物处置差异的因素。列举了使用抗癌药物的具体实例。描述了利用模型底物研究儿童肝脏药物代谢和肾脏排泄的情况并讨论了一些结果。介绍了遗传多态性药物代谢的意义，并描述了使用模型底物确定个体代谢表型的方法。提出了利用药代动力学数据来定义儿童抗癌药物的最大耐受全身暴露量而非最大耐受剂量的方法。
