Ontogeny of Drug-Metabolizing Enzymes.

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.

• Authors: Aarzoo Thakur, Md Masud Parvez, J Steven Leeder, Bhagwat Prasad
• Journal: Methods in molecular biology (Clifton, N.J.) (Methods Mol Biol) Vol. 2342 Pg. 551-593 ( 2021) ISSN: 1940-6029 [Electronic] United States
• PMID: 34272706 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)
• Copyright: © 2021. Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Enzymes
• Prescription Drugs

Topics

• Drug Dosage Calculations
• Enzymes (metabolism)
• Humans
• Infant
• Infant, Newborn
• Prescription Drugs (administration & dosage, pharmacokinetics, toxicity)