Department of Pharmacy, Radboud Institute for Health Sciences (RIHS), Radboud University Medical Centre, Nijmegen, the Netherlands.
MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London.
Ther Drug Monit. 2019 Aug;41(4):431-443. doi: 10.1097/FTD.0000000000000637.
This review summarizes the current dosing recommendations for antiretroviral (ARV) drugs in the international pediatric guidelines of the World Health Organization (WHO), US Department of Health and Human Services (DHHS), and Pediatric European Network for Treatment of AIDS (PENTA), and evaluates the research that informed these approaches. We further explore the role of data generated through therapeutic drug monitoring in optimizing the dosing of ARVs in children.
A PubMed search was conducted for the literature on ARV dosing published in English. In addition, the registration documentation of European Medicines Agency and the US Food and Drug Administration for currently used ARVs and studies referenced by the WHO, DHHS, and EMA guidelines were screened. Resulting publications were screened for papers containing data on the area under the concentration-time curve, trough concentration, and peak concentration. Studies with enrolled participants with a median or mean age of ≥18 years were excluded. No restriction on publishing date was applied.
Pediatric ARV dosing is frequently based on data obtained from small studies and is often simplified to facilitate dosing in the context of a public health approach. Pharmacokinetic parameters of pediatric ARVs are subject to high interpatient variation and this leads to a potential risk of underdosing or overdosing when drugs are used in real life. To ensure optimal use of ARVs and validate dosing recommendations for children, it is essential to monitor ARV dosing more thoroughly with larger sample sizes and to include diverse subpopulations. Therapeutic drug monitoring data generated in children, where available and affordable, have the potential to enhance our understanding of the appropriateness of simplified pediatric dosing strategies recommended using a public health approach and to uncover suboptimal dosing or other unanticipated issues postmarketing, further facilitating the ultimate goal of optimizing pediatric ARV treatment.
本综述总结了世界卫生组织（WHO）、美国卫生与公众服务部（DHHS）和儿科艾滋病治疗欧洲网络（PENTA）国际儿科指南中抗逆转录病毒（ARV）药物的当前剂量推荐，并评估了这些方法所依据的研究。我们进一步探讨了通过治疗药物监测生成的数据在优化儿童 ARV 剂量中的作用。
在 PubMed 上搜索以英文发表的关于 ARV 剂量的文献。此外，还筛选了欧洲药品管理局和美国食品和药物管理局目前使用的 ARV 的注册文件以及 WHO、DHHS 和 EMA 指南中引用的研究。对包含浓度-时间曲线下面积、谷浓度和峰浓度数据的出版物进行了筛选。排除了纳入中位数或平均年龄≥18 岁的参与者的研究。未对出版日期施加限制。
儿科 ARV 剂量通常基于从小型研究中获得的数据，并且经常简化以促进在公共卫生方法的背景下进行剂量调整。儿科 ARV 的药代动力学参数存在很大的个体间差异，这导致在实际应用中存在潜在的剂量不足或过量风险。为了确保 ARV 的最佳使用并验证儿童的剂量推荐，必须使用更大的样本量更全面地监测 ARV 剂量，并纳入更多样化的亚人群。在儿童中生成的治疗药物监测数据（如果可用且负担得起）有可能增强我们对简化的儿科剂量策略的理解，这些策略是基于公共卫生方法推荐的，并且可以发现剂量不足或其他预期之外的问题，从而进一步促进优化儿科 ARV 治疗的最终目标。
