Monoclonal antibodies (mAbs) and their derivatives are increasingly used in pediatric pharmacotherapy, and the number of antibody-based drug products with approved pediatric indications is continuously growing. In most instances, pediatric use is being pursued after the efficacy and safety of novel antibody medications have been established in adult indications. The pediatric extrapolation exercise that is frequently used in this context to bridge efficacy and safety from adults to children is oftentimes challenged through uncertainties and knowledge gaps in how to reliably extrapolate pharmacokinetics and clinical pharmacology of mAbs to different pediatric age groups, and how to derive age-appropriate dosing regimens that strike a balance between precision dosing and practicability. The article highlights some of the pharmacokinetic and clinical pharmacology challenges with regard to therapeutic use of mAbs and antibody derivatives in children, including immunogenicity events. Although considering body size-based differences in drug disposition can account for many of the perceived and actual differences in the distribution and elimination of antibody-based therapeutics between children and adults, increasing evidence suggests potential or actual age-associated differences beyond size differences, especially for young pediatric patients such as newborns and infants. To overcome age-associated differences in antibody disposition, various different dosing approaches have been applied to ensure safe and efficacious antibody exposure for pediatric populations of different ages. The development of such dosing regimens and the associated pathway to pediatric indication approval is illustrated in more detail for two antibody-based biologics, the fusion protein abatacept and the mAb tocilizumab.

中文翻译：

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单克隆抗体在儿科患者中的药代动力学和临床药理学

单克隆抗体（mAbs）及其衍生物越来越多地用于儿科药物治疗，具有批准的儿科适应症的基于抗体的药物产品数量不断增加。在大多数情况下，在成人适应症中确立了新型抗体药物的有效性和安全性后，正在寻求儿科使用。在这种情况下经常使用的儿科外推练习将成人与儿童的疗效和安全性联系起来，在如何可靠地将 mAb 的药代动力学和临床药理学外推到不同儿科年龄组以及如何推导年龄方面存在不确定性和知识差距，因此经常面临挑战- 适当的给药方案，在精确给药和实用性之间取得平衡。文章重点介绍了与 mAb 和抗体衍生物在儿童中的治疗应用相关的一些药代动力学和临床药理学挑战，包括免疫原性事件。尽管考虑基于身体大小的药物处置差异可以解释儿童和成人之间基于抗体的治疗方法的分布和消除的许多感知和实际差异，但越来越多的证据表明潜在或实际的年龄相关差异超出了大小差异，尤其是适用于新生儿和婴儿等年轻儿科患者。为了克服与年龄相关的抗体分布差异，已应用各种不同的剂量方法来确保不同年龄的儿科人群安全有效地接触抗体。