Department of Pediatric Surgery and Intensive Care, Erasmus MC-Sophia Children's Hospital, Dr. Molewaterplein 60, 3015 GJ, Rotterdam, The Netherlands.
Clin Pharmacokinet. 2013 May;52(5):333-45. doi: 10.1007/s40262-013-0041-1.
The aim of this review is to discuss our current understanding of the developmental changes of the drug-metabolizing enzyme cytochrome P450 (CYP) 3A and its impact on drug therapy. In the last 10 years, several methods have been used to study the ontogeny of specific CYP3A isoforms in vitro and in vivo. Although most studies confirm previous findings that CYP3A4/5 activity is low at birth and reaches adult values in the first years of life, there are still important gaps in our knowledge of the exact developmental patterns of individual CYP3A isoforms, especially in this age range. Moreover, most in vivo clinical studies have also failed to cover the whole pediatric age range. To date, this information gap still hampers the design of age-specific dosing guidelines of CYP3A substrate drugs, especially in neonates and infants. Innovative study methods, including opportunistic sampling and sensitive analytical assays used in combination with physiologically based pharmacokinetics, and population pharmacokinetic model concepts may help to improve our understanding of the ontogeny of CYP3A and aid the application of this knowledge in clinical practice.
本综述旨在讨论我们目前对药物代谢酶细胞色素 P450（CYP）3A 发育变化的理解及其对药物治疗的影响。在过去的 10 年中，已经使用了几种方法来研究体外和体内特定 CYP3A 同工酶的个体发育。尽管大多数研究证实了先前的发现，即 CYP3A4/5 活性在出生时较低，并且在生命的最初几年达到成人水平，但我们对个体 CYP3A 同工酶的确切发育模式的认识仍存在重要差距，尤其是在这个年龄段。此外，大多数体内临床研究也未能涵盖整个儿科年龄范围。迄今为止，这一信息差距仍然阻碍了 CYP3A 底物药物的特定年龄剂量指南的制定，尤其是在新生儿和婴儿中。创新的研究方法，包括机会性采样和结合生理药代动力学使用的敏感分析检测，以及群体药代动力学模型概念，可能有助于我们更好地了解 CYP3A 的个体发育，并有助于将这方面的知识应用于临床实践。
