Developmental pharmacology

Johannes N. van den Anker
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Abstract

Understanding the pharmacokinetics and pharmacodynamics of drugs used in psychopharmacology across the pediatric age spectrum from infants to adolescents represents a major challenge for clinicians. In pediatrics, treatment protocols use either standard dose reductions for these drugs for children below a certain age or use less conventional parameters such as weight for allometric dosing. The rationale behind this, however, is often lacking. In this review current available data on the developmental changes in absorption, distribution, metabolism, and elimination of drugs are presented with a specific focus on metabolic pathways, indicating significant differences in the development of enzymes involved in the biotransformation of drugs used in psychopharmacology. Major emphasis will be given to the genetic variation in CYP2D6 activity, the most important enzyme for the metabolism of many psychotropic medications. Finally, this review will summarize the role of the developmental pharmacologist in ensuring rational use of drugs in children with developmental disabilities and in translating pharmacological concepts from the bench to the clinic. © 2010 Wiley-Liss, Inc. Dev Disabil Res Rev 2010;16:233–238.

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发展药理学
了解精神药理学中使用的药物的药代动力学和药效学,横跨从婴儿到青少年的儿科年龄谱,是临床医生面临的主要挑战。在儿科,治疗方案要么对低于一定年龄的儿童使用这些药物的标准剂量减少,要么使用不太常规的参数,如体重异速给药。然而,这背后的基本原理往往缺乏。在这篇综述中,目前关于药物的吸收、分布、代谢和消除的发育变化的现有数据,特别关注代谢途径,表明在精神药理学中使用的药物的生物转化中涉及的酶的发育存在显著差异。重点将放在CYP2D6活性的遗传变异上,CYP2D6是许多精神药物代谢中最重要的酶。最后,本综述将总结发育药理学家在确保发育障碍儿童合理用药和将药理学概念从实验室转化为临床方面的作用。©2010 Wiley-Liss, IncDev - disability Rev 2010; 16:33 - 238。
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