Toward precision medicine in pediatric population using cytochrome P450 phenotyping approaches and physiologically based pharmacokinetic modeling
| Autor: | Youssef Daali, Gaëlle Magliocco, Caroline Flora Samer, Jules Alexandre Desmeules, Frédérique Rodieux |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Genotype
Pharmacogenomic Variants Pharmacokinetic modeling Less invasive Computational biology Biology Models Biological Pediatrics Substrate Specificity 03 medical and health sciences 0302 clinical medicine Cytochrome P-450 Enzyme System 030225 pediatrics Humans Drug Dosage Calculations Pharmacokinetics Dosing Precision Medicine Biological Variation Individual ddc:617 Age Factors Cytochrome P450 Precision medicine Isoenzymes Phenotype Biological Variation Population Pharmacogenetics Pediatrics Perinatology and Child Health biology.protein 030217 neurology & neurosurgery Pediatric population |
| Zdroj: | Pediatric Research (2019) |
| ISSN: | 0031-3998 |
| Popis: | The activity of drug-metabolizing enzymes (DME) shows high inter- and intra-individual variability. Genetic polymorphisms, exposure to drugs, and environmental toxins are known to significantly alter DME expression. In addition, the activity of these enzymes is highly age-dependent due to maturation processes that occur during development. Currently, there is a vast choice of phenotyping methods in adults using exogenous probes to characterize the activity of these enzymes. However, this can hardly be applied to children since it requires the intake of non-therapeutic xenobiotics. In addition, sampling may be challenging in the pediatric population for a variety of reasons: limited volume (e.g., blood), inappropriate sampling methods for age (e.g., urine), and metric requiring invasive or multiple blood samples. This review covers the main existing methods that can be used in the pediatric population to determine DME activity, with a particular focus on cytochrome P450 enzymes. Less invasive tools are described, including phenotyping using endogenous probes. Finally, the potential of pediatric model-informed precision dosing using physiologically based pharmacokinetic modeling is discussed. |
| Databáze: | OpenAIRE |
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