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Pediatric Pharmacotherapy pp 231–255Cite as

Pharmacokinetics and Pharmacodynamics of Drugs in Obese Pediatric Patients: How to Map Uncharted Clinical Territories

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 261))

Abstract

Clinicians are increasingly faced with challenges regarding the pharmacological treatment of obese pediatric patients. To provide guidance for these treatments, a better understanding of the impact of obesity on pharmacological processes in children is needed. Results on pharmacological studies in adults show however ambiguous patterns regarding the impact of obesity on ADME processes or on drug pharmacodynamics. Additionally, based on the limited research performed in obese pediatric patients, it becomes clear that findings from obese adults cannot be expected to always translate directly to similar findings in obese children. To improve knowledge on drug pharmacology in obese pediatric patients, studies should focus on quantifying the impact of maturation, obesity, and other relevant variables on primary pharmacological parameters and on disentangling systemic (renal and/or hepatic) and presystemic (gut and/or first-pass hepatic) clearance. For this, data is required from well-designed clinical trials that include patients with not only a wide range in age but also a range in excess body weight, upon oral and intravenous dosing. Population modelling approaches are ideally suitable for this purpose and can also be used to link the pharmacokinetics to pharmacodynamics and to derive drug dosing regimens. Generalizability of research findings can be achieved by including mechanistic aspects in the data analysis, for instance, using either extrapolation approaches in population modelling or by applying physiologically based modelling principles. It is imperative that more and smarter studies are performed in obese pediatric patients to provide safe and effective treatment for this special patient population.

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Authors and Affiliations

  1. Division of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands

    Elke H. J. Krekels & Catherijne A. J. Knibbe

  2. Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, The Netherlands

    Catherijne A. J. Knibbe

Authors
  1. Elke H. J. Krekels
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  2. Catherijne A. J. Knibbe
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Correspondence to Catherijne A. J. Knibbe .

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Editors and Affiliations

  1. Hospital for Children and Adolescents Center of Paediatric Research Department of Women and Child Health, University of Leipzig, Leipzig, Germany

    Wieland Kiess

  2. Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Department of Clinical Pharmacology, University Hospital Tüebingen, Tüebingen, Germany, Robert Bosch Gesellschaft fuer medizinische Forschung mbH, Stuttgart, Germany

    Matthias Schwab

  3. Children’s Hospital, University of Basel Children’s Hospital, Basel, Switzerland

    Johannes van den Anker

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Krekels, E.H.J., Knibbe, C.A.J. (2019). Pharmacokinetics and Pharmacodynamics of Drugs in Obese Pediatric Patients: How to Map Uncharted Clinical Territories. In: Kiess, W., Schwab, M., van den Anker, J. (eds) Pediatric Pharmacotherapy . Handbook of Experimental Pharmacology, vol 261. Springer, Cham. https://doi.org/10.1007/164_2019_250

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