Therapeutic drug monitoring of monoclonal antibodies: Applicability based on their pharmacokinetic properties

Chiyo K. Imamura

研究成果: Review article査読

21 被引用数 (Scopus)

抄録

Monoclonal antibodies (mAbs) have dramatically improved clinical outcomes for inflammatory and malignant diseases. The elimination route of mAbs is cellular uptake by nonspecific pinocytosis or receptor-mediated endocytosis followed by proteolytic degradation which is protected by neonatal Fc-receptor or mediated by antigenic target. There is a wide-interindividual variability in mAbs exposure due to target burden and other factors affecting unique their pharmacokinetics. It has been reported that higher exposures are correlated with better clinical outcomes of various therapeutic mAbs. On the other hand, flat exposure-efficacy relationships of anti-PD-1 antibodies nivolmab and pembrolizumab mean ensuring absolute maximum efficacy in each patient by the approved dose regardless of their large interpatient variability in pharmacokinetics. Administration of mAbs can induce production of anti-drug antibodies (ADAs), which impact on their pharmacokinetics and pharmacodynamics. In therapeutic drug monitoring (TDM) of mAbs, when total (free, soluble target bound and ADAs bound) mAbs concentration is measured, ADAs content (concentration/titer) should be also monitored because mAbs exists in inactive complex with ADAs. Along with determination of appropriated therapeutic windows taking into account ADAs content, treatment algorithms for TDM-guided clinical decision-making must be developed and prospectively shown to be superior to traditional clinical care for each mAb in each indication.

本文言語English
ページ(範囲)14-18
ページ数5
ジャーナルDrug Metabolism And Pharmacokinetics
34
1
DOI
出版ステータスPublished - 2019 2

ASJC Scopus subject areas

  • 薬理学
  • 薬科学
  • 薬理学(医学)

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