Morphine is a potent analgesic used for treating surgical and cancer pain. Despite being the drug of choice for the management of severe pain in children, the high interindividual variability in morphine pharmacokinetics limits its clinical utility to effectively relieve pain without adverse effects. This review was conducted to identify and describe all studies that have assessed the effect of genetic factors on the pharmacokinetics of morphine and its main metabolites in children. Embase and Medline databases were used to conduct the literature search, and the systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Of the 188 articles screened and after the application of specific inclusion and exclusion criteria, the review identified 8 studies. These studies suggest that genetic variants of selected metabolic enzymes and transporters may play a role in the observed interindividual variability in morphine plasma concentrations. Variants of the genes SLC22A1 and ABCC3 had the most supporting evidence for genetic variants that influence morphine and morphine metabolites pharmacokinetics. Although the available evidence suggests a potential genetic contribution to the variability in morphine concentration, the heterogeneity of the included studies in terms of experimental design and small sample sizes in some studies makes it challenging to propose the use of genetic biomarkers to personalize morphine dosing. This underscores the need to conduct more comprehensive and large-scale pharmacokinetic-pharmacogenetic studies to determine how or if genetic testing can optimize morphine safety and effectiveness in children.

中文翻译：

---

药物遗传学因素对儿科患者吗啡及其代谢物药代动力学的影响：系统评价。


吗啡是一种有效的镇痛药，用于治疗手术和癌症疼痛。尽管吗啡是治疗儿童严重疼痛的首选药物，但吗啡药代动力学的高度个体间变异性限制了其有效缓解疼痛而无不良反应的临床应用。本综述旨在确定和描述所有评估遗传因素对儿童吗啡及其主要代谢物药代动力学影响的研究。使用 Embase 和 Medline 数据库进行文献检索，系统评价根据系统评价和荟萃分析的首选报告项目 （PRISMA） 指南进行。在筛选的 188 篇文章中，在应用特定的纳入和排除标准后，该评价确定了 8 项研究。这些研究表明，选定代谢酶和转运蛋白的遗传变异可能在观察到的吗啡血浆浓度的个体间变异中发挥作用。基因 SLC22A1 和 ABCC3 的变异对影响吗啡和吗啡代谢物药代动力学的遗传变异具有最支持的证据。尽管现有证据表明吗啡浓度的可变性存在潜在的遗传贡献，但纳入研究在实验设计和一些研究中样本量小方面的异质性使得提议使用遗传生物标志物来个性化吗啡剂量具有挑战性。这强调了进行更全面和大规模的药代动力学-药物遗传学研究的必要性，以确定基因检测如何或是否可以优化儿童吗啡的安全性和有效性。