Stephenson Terence
University of Nottingham, Nottingham, UK.
Br J Clin Pharmacol. 2005 Jun;59(6):670-3. doi: 10.1111/j.1365-2125.2005.02445.x.
Children are not small adults. However, the main thesis of this review will be that children's responses to drugs have much in common with the responses in adults and indeed in other mammals. Often, it is assumed that drug effects differ in children but in reality this perception often arises because the drugs have not been adequately studied in paediatric populations of different ages and with different diseases. There may also be difficulties in measuring small but significant effects because the outcome measures are more difficult to assess in children. In some cases, stage of development can alter the action of, and response to, a drug - a truly age-dependent difference in pharmacodynamics. This may be true of both the desired action and adverse events. Examples are given. Programming by drugs is also a phenomenon almost exclusive to early life, i.e. permanent effects result from a stimulus applied at a sensitive point in development ('critical window'), often in fetal or neonatal life. Again, examples are discussed. Different pathophysiology, different disease variants, different pharmacodynamics, different 'host' response and different adverse drug reactions can all explain why some drugs behave differently in children. However, we need to explore ways to avoid re-inventing the wheel by determining how data from adult animal and human models can help inform research and practice for children.
儿童并非缩小版的成人。然而，本综述的主要论点是，儿童对药物的反应与成人乃至其他哺乳动物的反应有许多共同之处。通常，人们认为药物作用在儿童身上有所不同，但实际上这种认知往往源于药物在不同年龄和患有不同疾病的儿科人群中未得到充分研究。此外，测量微小但显著的效应可能也存在困难，因为在儿童中评估结局指标更具挑战性。在某些情况下，发育阶段会改变药物的作用及机体对药物的反应——这是药效学中真正依赖年龄的差异。这在预期作用和不良事件方面可能都是如此。文中给出了相关示例。药物编程也是一种几乎仅见于生命早期的现象，即发育过程中敏感阶段（通常是胎儿期或新生儿期）受到的刺激会产生永久性影响。同样，文中讨论了相关示例。不同的病理生理学、不同的疾病变体、不同的药效学、不同的“宿主”反应以及不同的药物不良反应，都可以解释为何某些药物在儿童身上的表现有所不同。然而，我们需要探索如何避免做无用功，即确定来自成年动物和人类模型的数据如何有助于为儿童研究和实践提供信息。
