Adolescent Dosing and Labeling Since the Food and Drug Administration Amendments Act of 2007
Adolescent Dosing and Labeling Since the Food and Drug Administration Amendments Act of 2007
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DOI：
10.1001/jamapediatrics.2013.465
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发表时间：
2013-10-01
期刊：
影响因子：
26.1
通讯作者：
Burckart, Gilbert J.
中科院分区：
文献类型：
--
作者：
Momper, Jeremiah D.;Mulugeta, Yeruk;Burckart, Gilbert J.
重要性 在儿科药物开发过程中，通常会在所有相关年龄组中进行专门的药代动力学研究，以支持后续疗效试验的剂量选择。据我们所知，之前没有对青少年进行深入的药代动力学研究的必要性进行过评估。 目的 比较美国食品和药物管理局 (FDA) 批准的成人和青少年药物剂量，并评估异速生长缩放在预测青少年人群药物清除率方面的效用。 设计 成人和青少年剂量和药物清除率数据来自 FDA 批准的药物标签和包含提交给 FDA 的儿科试验评论的公开数据库。对青少年和成年患者具有一致适应症的产品的剂量信息进行了比较。通过使用异速生长标度，根据成人药代动力学数据预测青少年药物清除率，并与观察值进行比较。 主要结果和措施 青少年和成人剂量信息和药物清除率。 结果 自 2007 年 FDA 修正案法案以来，已有 126 种独特的儿科研究产品提交给 FDA，其中 92 种至少有 1 种青少年适应症与成人适应症一致。在这 92 种产品中，87 种 (94.5%) 的成人和青少年患者剂量相同。对于这 92 种产品中的 18 种，建议青少年接受成人剂量的最低体重或体表面积阈值。异速生长缩放预测青少年药物清除率的总体平均绝对百分比误差为 17.0%。 结论和相关性自 2007 年 FDA 修正案法案以来，已批准的成人和青少年药物剂量与研究的青少年适应症产品中的 94.5% 相当。异速生长缩放可能是一个有用的工具，可以避免儿科药物开发期间在青少年群体中进行不必要的专门药代动力学研究，尽管青少年的每个开发计划都需要与 FDA 充分讨论药物剂量。
IMPORTANCE During pediatric drug development, dedicated pharmacokinetic studies are generally performed in all relevant age groups to support dose selection for subsequent efficacy trials. To our knowledge, no previous assessments regarding the need for an intensive pharmacokinetic study in adolescents have been performed.OBJECTIVES To compare US Food and Drug Administration (FDA)-approved adult and adolescent drug dosing and to assess the utility of allometric scaling for the prediction of drug clearance in the adolescent population.DESIGN Adult and adolescent dosing and drug clearance data were obtained from FDA-approved drug labels and publicly available databases containing reviews of pediatric trials submitted to the FDA. Dosing information was compared for products with concordant indications for adolescent and adult patients. Adolescent drug clearance was predicted from adult pharmacokinetic data by using allometric scaling and compared with observed values.MAIN OUTCOMES AND MEASURES Adolescent and adult dosing information and drug clearance.RESULTS There were 126 unique products with pediatric studies submitted to the FDA since the FDA Amendments Act of 2007, of which 92 had at least 1 adolescent indication concordant with an adult indication. Of these 92 products, 87 (94.5%) have equivalent dosing for adults and adolescent patients. For 18 of these 92 products, a minimum weight or body surface area threshold is recommended for adolescents to receive adult dosing. Allometric scaling predicted adolescent drug clearance with an overall mean absolute percentage error of 17.0%.CONCLUSIONS AND RELEVANCE Approved adult and adolescent drug dosing is equivalent for 94.5% of products with an adolescent indication studied since the FDA Amendments Act of 2007. Allometric scaling may be a useful tool to avoid unnecessary dedicated pharmacokinetic studies in the adolescent population during pediatric drug development, although each development program in adolescents requires a full discussion of drug dosing with the FDA.