School of Pharmacy, Institute of Clinical Sciences, University of Birmingham, Edgbaston, B15 2TT, UK.
Division of Quantitative Methods and Modelling, Office of Research and Standard, Office of Generic Drug Products, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland, 20993, USA.
AAPS J. 2021 Apr 21;23(3):57. doi: 10.1208/s12248-021-00592-y.
Generally, bioequivalence (BE) studies of drug products for pediatric patients are conducted in adults due to ethical reasons. Given the lack of direct BE assessment in pediatric populations, the aim of this work is to develop a database of BE and relative bioavailability (relative BA) studies conducted in pediatric populations and to enable the identification of risk factors associated with certain drug substances or products that may lead to failed BE or different pharmacokinetic (PK) parameters in relative BA studies in pediatrics. A literature search from 1965 to 2020 was conducted in PubMed, Cochrane Library, and Google Scholar to identify BE studies conducted in pediatric populations and relative BA studies conducted in pediatric populations. Overall, 79 studies covering 37 active pharmaceutical ingredients (APIs) were included in the database: 4 bioequivalence studies with data that passed BE evaluations; 2 studies showed bioinequivalence results; 34 relative BA studies showing comparable PK parameters, and 39 relative BA studies showing differences in PK parameters between test and reference products. Based on the above studies, common putative risk factors associated with differences in relative bioavailability (DRBA) in pediatric populations include age-related absorption effects, high inter-individual variability, and poor study design. A database containing 79 clinical studies on BE or relative BA in pediatrics has been developed. Putative risk factors associated with DRBA in pediatric populations are summarized.
一般来说，由于伦理原因，儿科患者的药物产品的生物等效性 (BE) 研究是在成年人中进行的。鉴于儿科人群中缺乏直接的 BE 评估，本工作的目的是建立一个在儿科人群中进行的 BE 和相对生物利用度 (relative BA) 研究的数据库，并能够识别与某些药物物质或产品相关的风险因素，这些因素可能导致 BE 失败或儿科相对 BA 研究中出现不同的药代动力学 (PK) 参数。在 PubMed、Cochrane Library 和 Google Scholar 中进行了从 1965 年到 2020 年的文献检索，以确定在儿科人群中进行的 BE 研究和在儿科人群中进行的相对 BA 研究。总体而言，该数据库共纳入了 79 项涵盖 37 种活性药物成分 (API) 的研究：4 项具有通过 BE 评估的数据的生物等效性研究；2 项显示生物不等效结果的研究；34 项显示可比 PK 参数的相对 BA 研究，以及 39 项显示试验和参比产品之间 PK 参数存在差异的相对 BA 研究。基于上述研究，与儿科人群中相对生物利用度 (DRBA) 差异相关的常见假定风险因素包括与年龄相关的吸收效应、个体间变异性大以及研究设计不佳。已经开发了一个包含 79 项儿科 BE 或相对 BA 临床研究的数据库。总结了与儿科人群中 DRBA 相关的假定风险因素。
