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Pharmacokinetics and Pharmacokinetic–Pharmacodynamic Relationships of Monoclonal Antibodies in Children

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Abstract

Monoclonal antibodies (mAbs) constitute a therapeutically and economically important drug class with increasing use in both adult and paediatric patients. The rather complex pharmacokinetic and pharmacodynamic properties of mAbs have been extensively reviewed in adults. In children, however, limited information is currently available. This paper aims to comprehensively review published pharmacokinetic and pharmacokinetic–pharmacodynamic studies of mAbs in children. The current status of mAbs in the USA and in Europe is outlined, including a critical discussion of the dosing strategies of approved mAbs. The pharmacokinetic properties of mAbs in children are exhaustively summarised along with comparisons to reports in adults: for each pharmacokinetic process, we discuss the general principles and mechanisms of the pharmacokinetic/pharmacodynamic characteristics of mAbs, as well as key growth and maturational processes in children that might impact these characteristics. Throughout this review, considerable knowledge gaps are identified, especially regarding children-specific properties that influence pharmacokinetics, pharmacodynamics and immunogenicity. Furthermore, the large heterogeneity in the presentation of pharmacokinetic/pharmacodynamic data limited clinical inferences in many aspects of paediatric mAb therapy. Overall, further studies are needed to fully understand the impact of body size and maturational changes on drug exposure and response. To maximise future knowledge gain, we propose a ‘Guideline for Best Practice’ on how to report pharmacokinetic and pharmacokinetic–pharmacodynamic results from mAb studies in children which also facilitates comparisons. Finally, we advocate the use of more sophisticated modelling strategies (population analysis, physiology-based approaches) to appropriately characterise pharmacokinetic–pharmacodynamic relationships of mAbs and, thus, allow for a more rational use of mAb in the paediatric population.

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Notes

  1. Many other abbreviations are also used in the literature, e.g. HAMA (human anti-murine antibodies), HACA (human anti-chimeric antibodies), HAHA (human anti-human(ised) antibodies); for some mAbs, specific abbreviations have been introduced, e.g. ATI (antibodies towards infliximab).

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Acknowledgments

The authors wish to thank Corina Becker (Bayer Pharma) for fruitful discussion, Tamara Richter and Caroline Fongern (both Freie Universitaet Berlin) for their support during the literature search, and the reviewers of this manuscript for their valuable input into the manuscript. No sources of funding were used for the preparation of this review. The authors have no conflict of interest to declare.

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  1. Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Kelchstr. 31, 12169, Berlin, Germany

    Helena Edlund, Johanna Melin, Zinnia P. Parra-Guillen & Charlotte Kloft

  2. Graduate Research Training Program, PharMetrX, Berlin, Germany

    Helena Edlund & Johanna Melin

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  1. Helena Edlund
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Edlund, H., Melin, J., Parra-Guillen, Z.P. et al. Pharmacokinetics and Pharmacokinetic–Pharmacodynamic Relationships of Monoclonal Antibodies in Children. Clin Pharmacokinet 54, 35–80 (2015). https://doi.org/10.1007/s40262-014-0208-4

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