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In Vivo Modeling of the Morbid Human Genome using Danio rerio

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Developmental pharmacogenomics.

Kathleen A Neville¹, Mara L Becker, Jennifer L Goldman

¹Department of Pediatrics, University of Missouri - Kansas City, Kansas City, MO, USA. kaneville@cmh.edu

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|February 16, 2011

Summary

This summary is machine-generated.

Pediatric pharmacogenomics considers how a child's development influences drug response. Understanding ontogeny is key to predicting drug efficacy and safety in early life.

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Area of Science:

Pharmacogenomics
Pediatric Pharmacology
Developmental Biology

Background:

Individual responses to medications vary significantly in children and adults.
Drug disposition and action are influenced by a complex interplay of genetic and developmental factors.
Ontogeny, the process of development, significantly impacts pharmacokinetic and pharmacodynamic variability in pediatric populations.

Purpose of the Study:

To review the role of ontogeny in pediatric pharmacogenomics.
To examine how developmental changes affect drug-metabolizing enzymes and transporters.
To elucidate the impact of these changes on the drug exposure-response relationship in early life.

Main Methods:

Literature review focusing on pharmacogenomics and ontogeny in pediatric populations.
Analysis of studies investigating drug-metabolizing enzymes and transporter expression during development.
Examination of the relationship between genetic variations, ontogeny, and drug response.

Main Results:

Ontogeny significantly alters the expression and activity of drug-metabolizing enzymes and transporters in children.
These developmental changes lead to substantial interindividual variability in drug pharmacokinetics and pharmacodynamics.
Genetic factors interact with ontogeny to shape the drug exposure-response relationship from infancy through childhood.

Conclusions:

Pharmacogenomic studies in children must integrate the influence of ontogeny.
Understanding developmental changes in drug metabolism and transport is crucial for optimizing pediatric drug therapy.
Tailoring drug selection and dosage based on genotype and developmental stage can improve treatment outcomes and safety in pediatric patients.