Seely John Curtis
Experimental Pathology Laboratories, Inc., P.O. Box 12766, Research Triangle Park, NC 27709, USA.
J Toxicol Pathol. 2017 Apr;30(2):125-133. doi: 10.1293/tox.2017-0006. Epub 2017 Feb 11.
Nonclinical juvenile animal tests perform a valuable role in determining adverse drug effects during periods of organogenesis and/or functional maturation. Developmental anatomic and functional maturation time points are important to consider between juveniles and adults when regarding different organ toxicities in response to drug administration. The kidney is an example of a major organ that has differences in these time points in comparing juveniles to adults and in contrasting humans to laboratory animal species. Toxicologic pathologists, involved in juvenile studies, need to be aware of these time points which are age-related exposure periods of sensitivity to drug toxicity. Age-related developmental anatomic and functional maturation are factors which can affect the way that a drug is absorbed, distributed, metabolized, and excreted (ADME). Changes to any component of ADME may alter drug toxicity resulting in kidney abnormalities, nephrotoxicity, or maturational disorders. Juvenile animal kidneys may either be less resistant or more resistant to known adult nephrotoxic drug effects. Furthermore, drug toxicity observed in juvenile animal kidneys may not always correspond to similar toxicities in humans. Juvenile animal nonclinical toxicology studies targeting the kidneys have to be carefully planned to attain the maximum knowledge from each study.
非临床幼年动物试验在确定器官发生和/或功能成熟期间的药物不良反应方面发挥着重要作用。在考虑药物给药后不同器官毒性时，幼年和成年动物之间发育解剖学和功能成熟的时间点很重要。肾脏就是一个主要器官的例子，在比较幼年与成年动物以及对比人类与实验动物物种时，这些时间点存在差异。参与幼年动物研究的毒理病理学家需要了解这些时间点，它们是与年龄相关的对药物毒性敏感的暴露期。与年龄相关的发育解剖学和功能成熟是可以影响药物吸收、分布、代谢和排泄（ADME）方式的因素。ADME任何组成部分的变化都可能改变药物毒性，导致肾脏异常、肾毒性或成熟障碍。幼年动物的肾脏对已知的成年肾毒性药物作用可能抵抗力较弱，也可能更强。此外，在幼年动物肾脏中观察到的药物毒性不一定总是与人类的类似毒性相对应。针对肾脏的幼年动物非临床毒理学研究必须精心规划，以便从每项研究中获取最大的知识。
