Pharmacogenetics and pharmacogenomics.
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.
Leeder
J S
JS
Section 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
D001189:Aryl Hydrocarbon Hydroxylases; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism / Q000493:pharmacokinetics; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism / Q000493:pharmacokinetics; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism / Q000493:pharmacokinetics; D014453:Glucuronosyltransferase / Q000378:metabolism; D006801:Humans; D015278:Intensive Care Units, Pediatric / Q000458:organization & administration; D008780:Methyltransferases / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism / Q000493:pharmacokinetics; D010597:Pharmacogenetics; D010599:Pharmacokinetics; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000378:metabolism / Q000493:pharmacokinetics
D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C504573:CYP1A2 protein, human; C045793:CYP2C19 protein, human; C104464:CYP3A protein, human; D019388:Cytochrome P-450 CYP1A2; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; D039181:Steroid 16-alpha-Hydroxylase; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D014453:Glucuronosyltransferase