Rodieux Frédérique, Daali Youssef, Rollason Victoria, Samer Caroline F, Ing Lorenzini Kuntheavy
Division of Clinical Pharmacology and Toxicology, Department of Anesthesiology, Pharmacology, Emergency Medicine and Intensive care, Geneva University Hospitals, Geneva, Switzerland.
School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland.
Front Pharmacol. 2023 Feb 27;14:1130100. doi: 10.3389/fphar.2023.1130100. eCollection 2023.
Pharmacokinetics varies widely between children. Many factors play an important role in this variability, such as ontogeny, pharmacogenetics, gender, comorbidities, and drug-drug interactions. Significant work has already been done in adults to understand the impact of genetic polymorphisms on drug-metabolizing enzyme activity and drug response. Data remain poor in children due to ontogeny that impacts genotyping-phenotyping correlation and the difficulty enrolling children in prospective studies. Our study aimed to describe the use of cytochromes P450 (CYP) phenotyping and/or genotyping tests in children in a real-life setting and assess the correlation between the genotype and the phenotype. We reviewed the results of tests performed between January 2005 and December 2020. Fifty-two children were genotyped and/or phenotyped. Four patients were excluded from the present analysis as they only underwent ABCB1 genotyping, without CYP testing. Of the remainder, 18 underwent simultaneous CYP genotyping and phenotyping, while 17 underwent CYP genotyping only, and 13 underwent CYP phenotyping only. In all cases, investigations were performed after the following situations: insufficient clinical response to treatment, low plasma concentrations, and adverse drug reactions (ADR). The vast majority of cases were related to immunosuppressive or antipsychotic therapy. Genotyping and/or phenotyping explained or contributed to the aforementioned clinical events in 56% of cases. The correlation between the genotype and the phenotype showed variability depending on the assessed cytochrome. In several cases, the phenotype did not correspond to the genotype because of comedications. In conclusion, there is clearly value in guiding drug based on CYP activity in children.
儿童的药代动力学差异很大。许多因素在这种变异性中起重要作用，如个体发育、药物遗传学、性别、合并症以及药物相互作用。在成人中已经开展了大量工作来了解基因多态性对药物代谢酶活性和药物反应的影响。由于个体发育影响基因分型与表型的相关性以及招募儿童参与前瞻性研究存在困难，儿童方面的数据仍然匮乏。我们的研究旨在描述在实际临床环境中细胞色素P450（CYP）表型和/或基因分型检测在儿童中的应用，并评估基因型与表型之间的相关性。我们回顾了2005年1月至2020年12月期间进行的检测结果。52名儿童进行了基因分型和/或表型分析。4名患者仅接受了ABCB1基因分型，未进行CYP检测，因此被排除在本分析之外。其余患者中，18名同时进行了CYP基因分型和表型分析，17名仅进行了CYP基因分型，13名仅进行了CYP表型分析。在所有病例中，检测均在以下情况后进行：治疗临床反应不足、血浆浓度低以及药物不良反应（ADR）。绝大多数病例与免疫抑制或抗精神病治疗有关。基因分型和/或表型分析在56%的病例中解释了或促成了上述临床事件。基因型与表型之间的相关性因所评估的细胞色素而异。在一些病例中，由于合并用药，表型与基因型不相符。总之，基于儿童CYP活性指导用药显然具有价值。
