Kauffman R E, Kearns G L
Department of Pediatrics, Wayne State University School of Medicine, Children's Hospital of Michigan, Detroit.
Clin Pharmacokinet. 1992 Jul;23(1):10-29. doi: 10.2165/00003088-199223010-00002.
Important advances in paediatric clinical pharmacology have been made over the past 2 decades. However, there remains a reluctance to pursue pharmacodynamic and pharmacokinetic studies in children and, consequently, many important therapeutic agents have not been adequately studied in this population. Age-related pharmacokinetic/pharmacodynamic studies are not only essential to provide optimal drug therapy for children, but are quite feasible. Usually, paediatric pharmacokinetic studies are conducted in children receiving treatment for a specific medical condition. The approach to soliciting participation of paediatric subjects requires special sensitivity to the fears and anxieties of the child and the parents. Factors influencing subject enrollment and suggestions to enhance enrollment into study protocols are discussed. Pharmacokinetic/pharmacodynamic studies require repeated measurements over time and often entail obtaining multiple blood and urine samples. Techniques for reducing sample volume and number of necessary samples while minimising the discomfort and fear associated with obtaining multiple samples include the development of highly sensitive analytical methods to measure drug concentrations in small volume samples. The number of samples obtained from individual subjects can be minimised by using pharmacokinetic analytical approaches such as the nonlinear mixed effect model (NONMEM) which allows estimation of pharmacokinetic characteristics of a population using limited data from each subject. In addition, less invasive methods to measure drug metabolism/elimination such as salivary sampling, transcutaneous collection and breath analysis have been applied to the study of certain drugs. Children are a particularly vulnerable population because of their limited cognitive abilities and dependence on adults. Thus, they must be afforded greater protection from exploitation as research subjects than that provided to adults.
在过去20年里，儿科临床药理学取得了重要进展。然而，人们仍然不愿意在儿童中开展药效学和药代动力学研究，因此，许多重要的治疗药物在这一人群中尚未得到充分研究。与年龄相关的药代动力学/药效学研究不仅对于为儿童提供最佳药物治疗至关重要，而且是完全可行的。通常，儿科药代动力学研究是在因特定疾病接受治疗的儿童中进行的。征求儿科受试者参与的方法需要对儿童及其父母的恐惧和焦虑特别敏感。讨论了影响受试者入组的因素以及提高研究方案入组率的建议。药代动力学/药效学研究需要随时间进行重复测量，并且通常需要采集多个血液和尿液样本。在尽量减少与采集多个样本相关的不适和恐惧的同时，减少样本量和所需样本数量的技术包括开发高灵敏度分析方法来测量小体积样本中的药物浓度。通过使用药代动力学分析方法，如非线性混合效应模型（NONMEM），可以减少从个体受试者获得的样本数量，该模型允许使用每个受试者的有限数据来估计总体的药代动力学特征。此外，唾液采样、经皮采集和呼吸分析等侵入性较小的药物代谢/消除测量方法已应用于某些药物的研究。由于儿童认知能力有限且依赖成年人，他们是一个特别脆弱的群体。因此，与给予成年人的保护相比，他们作为研究对象必须得到更大的保护以免受剥削。
