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Ontogeny of Drug-Metabolizing Enzymes

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Enzyme Kinetics in Drug Metabolism

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2342))

Abstract

Almost 50% of prescription drugs lack age-appropriate dosing guidelines and therefore are used “off-label.” Only ~10% drugs prescribed to neonates and infants have been studied for safety or efficacy. Immaturity of drug metabolism in children is often associated with drug toxicity. This chapter summarizes data on the ontogeny of major human metabolizing enzymes involved in oxidation, reduction, hydrolysis, and conjugation of drugs. The ontogeny data of individual drug-metabolizing enzymes are important for accurate prediction of drug pharmacokinetics and toxicity in children. This information is critical for designing clinical studies to appropriately test pharmacological hypotheses and develop safer pediatric drugs, and to replace the long-standing practice of body weight- or surface area-normalized drug dosing. The application of ontogeny data in physiologically based pharmacokinetic model and regulatory submission are discussed.

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Acknowledgement

B.P. and M.M.P. were supported by the National Institutes of Health (NIH) grant (R01 HD081299).

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Author notes

  1. Aarzoo Thakur and Md Masud Parvez contributed equally to this work.

Authors and Affiliations

  1. Innovations in Food and Chemical Safety, Agency for Science, Technology and Research, Singapore City, Singapore

    Aarzoo Thakur

  2. Skin Research Institute of Singapore, Agency for Science, Technology and Research, Singapore City, Singapore

    Aarzoo Thakur

  3. Department of Pharmaceutical Sciences, Washington State University, Spokane, WA, USA

    Md Masud Parvez & Bhagwat Prasad

  4. Division of Clinical Pharmacology, Toxicology, and Therapeutic Innovation, Department of Pediatrics, Children’s Mercy Kansas City and University of Missouri-Kansas City, Kansas City, MO, USA

    J. Steven Leeder

Authors
  1. Aarzoo Thakur
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  2. Md Masud Parvez
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  3. J. Steven Leeder
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  4. Bhagwat Prasad
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Corresponding authors

Correspondence to J. Steven Leeder or Bhagwat Prasad .

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Editors and Affiliations

  1. Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA, USA

    Swati Nagar

  2. Translational Medicine, Novartis Institutes for Biomedical Research, Inc., Cambridge, MA, USA

    Upendra A. Argikar

  3. Independent, Harleysville, PA, USA

    Donald Tweedie

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Thakur, A., Parvez, M.M., Leeder, J.S., Prasad, B. (2021). Ontogeny of Drug-Metabolizing Enzymes. In: Nagar, S., Argikar, U.A., Tweedie, D. (eds) Enzyme Kinetics in Drug Metabolism. Methods in Molecular Biology, vol 2342. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1554-6_18

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  • DOI: https://doi.org/10.1007/978-1-0716-1554-6_18

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