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Clinical Pharmacology and Pharmacometrics to Better Understand Physiological Changes During Pregnancy and Neonatal Life

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Pediatric Pharmacotherapy

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

Abstract

Pregnant women, fetuses, and newborns are particularly vulnerable patient populations. During pregnancy, the body is subject to physiological changes that influence the pharmacokinetics and pharmacodynamics of drugs. Inappropriate dosing in pregnant women can result in sub-therapeutic or toxic effects, putting not only the pregnant woman but also her fetus at risk. During neonatal life, maturation processes also affect pharmacokinetics and pharmacodynamics of drugs. Inappropriate dosing in newborns leads not only to short-term complications but can also have a negative impact on the long-term development of infants and children. For these reasons, it is crucial to characterize physiological changes in pregnant women, describe placental transfer kinetics of drugs, and describe physiological changes related to the transition from intrauterine to extrauterine life and maturation processes in preterm and term neonates. Quantitative pharmacological approaches such as pharmacometric and physiologically-based modeling and model-based simulations can be useful to better understand and predict such physiological changes and their effects on drug exposure and response. This review article (1) gives an overview of physiological changes in pregnant women, their fetuses, and (pre)term neonates, (2) presents case studies to illustrate applications of new modeling and simulation approaches, and (3) discusses challenges and opportunities in optimizing and personalizing treatments during pregnancy and neonatal life.

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Acknowledgment

TvD, KE, GK, JvdA, and MP would like to thank the Eckenstein-Geigy Foundation in Basel, Switzerland, for their financial support.

Author information

Authors and Affiliations

  1. Pediatric Pharmacology and Pharmacometrics, University of Basel Children’s Hospital, Basel, Switzerland

    Tamara van Donge, Katrina Evers, Gilbert Koch, John van den Anker & Marc Pfister

  2. Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands

    John van den Anker

  3. Division of Clinical Pharmacology, Children’s National Health System, Washington, DC, USA

    John van den Anker

  4. Certara LP, Princeton, NJ, USA

    Marc Pfister

Authors
  1. Tamara van Donge
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  2. Katrina Evers
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  3. Gilbert Koch
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  4. John van den Anker
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  5. Marc Pfister
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Corresponding author

Correspondence to Tamara van Donge .

Editor information

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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van Donge, T., Evers, K., Koch, G., van den Anker, J., Pfister, M. (2019). Clinical Pharmacology and Pharmacometrics to Better Understand Physiological Changes During Pregnancy and Neonatal Life. 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_210

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