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Pharmacogenetics and pharmacogenomics
1Section of Developmental Pharmacology and Experimental Therapeutics, Division of Clinical Pharmacology and Toxicology, Children's Mercy Hospital and Clinics, University of Kansas Medical Center, Kansas City, Kansas, USA. sleeder@cmh.edu
Insights
Pediatric pharmacogenetics, the study of how genes affect drug response in children, is in its early stages. Comprehensive research into genetic factors influencing drug transport and metabolism is crucial for optimizing pediatric pharmacotherapy.
Area of Science:
- Pharmacogenomics and Pharmacogenetics
- Pediatric Critical Care Medicine
- Developmental Pharmacology
Background:
- Pharmacogenetics and pharmacogenomics are emerging fields within pediatric pharmacotherapy.
- Pediatric pharmacogenetics is currently in its nascent stages of development.
- Existing pharmacokinetic data often relies on single CYP pathways, offering limited insight into developmental drug metabolism.
Purpose of the Study:
- To introduce the concepts of pharmacogenetics and pharmacogenomics in the pediatric intensive care unit (ICU) setting.
- To highlight the developmental aspect of pharmacogenetics in children.
- To emphasize the need for comprehensive investigation into factors influencing drug response in pediatric patients.
Main Methods:
- Review of available pharmacokinetic data for drugs primarily metabolized by single CYP pathways.
- Analysis of how developmental changes, disease, environmental factors, and co-medications influence drug biotransformation.
- Conceptual framework for understanding drug response as a result of complex genetic interactions.
Main Results:
- Pharmacogenetics in pediatrics primarily concerns phenotypic changes during growth and development.
- Drug biotransformation 'phenotype' is influenced by various external and internal factors beyond genetics.
- Drug response is a multifactorial outcome involving genes related to drug transport, metabolism, receptors, and signaling.
Conclusions:
- Optimization of pediatric pharmacotherapy requires a thorough understanding of developmental changes in drug transport, metabolism, and other genetic pathways.
- Realizing the full potential of pharmacogenetics and pharmacogenomics for rational therapeutics in children necessitates further extensive research.
- Current understanding is limited by the early stage of pediatric pharmacogenetics research.
Abstract:
This article introduces pharmacogenetics and pharmacogenomics in the context of pharmacotherapy in the pediatric ICU setting. As an independent discipline (if it can be considered as such), pediatric or developmental pharmacogenetics is essentially at a neonatal stage. Available pharmacokinetic data derived from studies of drugs that are largely dependent on a single CYP pathway for their elimination provide initial assessments of the developmental profile of that particular CYP isoform. Essentially then, pharmacogenetics in a pediatric context refers to the changes in phenotype that occur as a child grows and develops. Furthermore, the apparent drug biotransformation "phenotype" may be influenced by disease (infection), environmental factors (diet and environmental contaminants) and concurrent medications; however, drug response is a function of the complex interplay among genes involved in drug transport, drug biotransformation, receptors, and signal transduction processes, among others. Therefore, optimization of pediatric pharmacotherapy necessarily requires that developmental changes in each of these areas and not just drug biotransformation be investigated thoroughly before the promise of pharmacogenetics and pharmacogenomics for rational therapeutics can be realized in children.