Gasthuys Elke, Vandecasteele Tim, De Bruyne Pauline, Walle Johan Vande, De Backer Patrick, Cornillie Pieter, Devreese Mathias, Croubels Siska
Department of Toxicology, Pharmacology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
Curr Pharm Des. 2016;22(26):4069-85. doi: 10.2174/1381612822666160303111031.
Pediatric drug research is still substandard, not reaching the same quality level as adult drug research. Despite the efforts made by the Food and Drug Administration and European Medicines Agency to reduce off-label use in children, the lack of clinical studies involving the pediatric population still stands. Pharmacokinetic and pharmacodynamics studies (PK/PD) taking growth and maturation into account are necessary to rationalize dosing strategies in children. Currently, traditional animal models such as rats, mice, dogs and primates are used to conduct pharmacokinetic and pharmacodynamic studies, however age-related trials are rather uncommon. Moreover, these species have several shortcomings as animal models, such as a different physiology and anatomy of the gastrointestinal tract in dogs or the ethical aspects for the use of primates. In contrast, piglets might be potential biomedical pediatric animal models because of the good resemblance with humans, anatomically, physiologically and biochemically. This review summarizes the comparative anatomy and physiology and postnatal development of piglets and infants, focusing on six major topics, namely growth, cardiovascular system, gastrointestinal tract, liver, kidney and integument. Furthermore, the application of piglets as animal model in pediatric PK/PD research is discussed.
儿科药物研究仍未达标，未达到与成人药物研究相同的质量水平。尽管美国食品药品监督管理局和欧洲药品管理局为减少儿童超说明书用药做出了努力，但涉及儿科人群的临床研究仍然匮乏。考虑到生长和发育的药代动力学和药效学研究（PK/PD）对于合理制定儿童给药策略是必要的。目前，大鼠、小鼠、犬类和灵长类等传统动物模型被用于进行药代动力学和药效学研究，然而与年龄相关的试验相当少见。此外，这些物种作为动物模型存在一些缺点，比如犬类胃肠道的生理和解剖结构不同，或者使用灵长类动物存在伦理问题。相比之下，仔猪在解剖学、生理学和生物化学方面与人类有诸多相似之处，可能是潜在的生物医学儿科动物模型。本综述总结了仔猪和婴儿的比较解剖学、生理学及出生后的发育情况，重点关注六个主要主题，即生长、心血管系统、胃肠道、肝脏、肾脏和皮肤。此外，还讨论了仔猪作为动物模型在儿科PK/PD研究中的应用。
