CYP3A4 drug metabolism considerations in pediatric pharmacotherapy

IF 2.6 4区医学 Q3 CHEMISTRY, MEDICINAL

Medicinal Chemistry Research Pub Date : 2024-12-05 DOI:10.1007/s00044-024-03360-7

Marin Vander Schaaf, Kyrle Luth, Danyelle M. Townsend, Katherine H. Chessman, Catherine M. Mills, Sandra S. Garner, Yuri K. Peterson

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Abstract

Cytochrome P450 3A4 (CYP3A4) is a crucial enzyme involved in the Phase I metabolism of numerous medications used in clinical practice. Its potential significance in pediatric pharmacotherapy is underscored by the unique metabolic profile of children, which differs markedly from adults, especially in neonates, infants, and young children due to developmental changes in enzyme activity. This review explores the critical role of CYP3A4 in the metabolism of drugs used in the pediatric population, with a particular focus on combination drug therapies. Given the high potential for drug-drug interactions in combination therapies, understanding the modulation of CYP3A4 activity is essential for optimizing therapeutic outcomes and minimizing adverse effects. This paper further examines the structural similarities between these medications and bergamottin, a known CYP3A4 inhibitor found in citric fruits such as grapefruit. Variability in CYP3A4 activity, influenced by genetic polymorphisms, developmental stage, and external factors, necessitates careful consideration in the prescribing and management of drugs in children. This review corroborates the need for personalized medicine approaches and enhanced pharmacovigilance to ensure the safe and effective use of CYP3A4-metabolized drugs in the pediatric population.

Graphical Abstract

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细胞色素 P450 3A4 (CYP3A4) 是一种重要的酶，参与临床上许多药物的 I 期代谢。由于儿童独特的代谢特征，特别是新生儿、婴儿和幼儿体内酶活性的发育变化，儿童的代谢特征与成人明显不同，这就凸显了 CYP3A4 在儿科药物治疗中的潜在意义。本综述探讨了 CYP3A4 在儿科用药代谢中的关键作用，尤其关注联合用药治疗。鉴于联合用药疗法中药物间相互作用的可能性很大，了解 CYP3A4 活性的调节对于优化治疗效果和减少不良反应至关重要。本文进一步研究了这些药物与佛手柑素之间的结构相似性，佛手柑素是一种已知的 CYP3A4 抑制剂，存在于葡萄柚等柠檬类水果中。受基因多态性、发育阶段和外部因素的影响，CYP3A4 活性存在差异，因此在给儿童开处方和管理药物时必须慎重考虑。本综述证实了个性化医疗方法和加强药物警戒的必要性，以确保在儿童群体中安全有效地使用 CYP3A4 代谢药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Medicinal Chemistry Research 医学-医药化学

CiteScore

4.70

自引率

3.80%

发文量

162

审稿时长

5.0 months

期刊介绍： Medicinal Chemistry Research (MCRE) publishes papers on a wide range of topics, favoring research with significant, new, and up-to-date information. Although the journal has a demanding peer review process, MCRE still boasts rapid publication, due in part, to the length of the submissions. The journal publishes significant research on various topics, many of which emphasize the structure-activity relationships of molecular biology.