Pharmacogenomics and renal drug disposition in the newborn.
Genetic polymorphisms in the genes coding for drug metabolizing enzymes, drug transporters, and drug receptors are major determinants of an individual's response to drugs. The potential interactions of pharmacogenomics of renal drug transporters and drug receptors with renal drug disposition and the immature kidneys are briefly reviewed. Examples of gene polymorphisms seen in the RAAS (renin angiotensin system), beta-adrenergic receptors, dopamine receptors and cytochrome P450 and their potential clinical impact are discussed. The human newborn has deficient hepatic and renal drug metabolism and disposition. This immaturity in drug-handling capacity may potentially be superimposed to genetic polymorphisms determining drug metabolism and transport thereby substantially increasing interpatient variability in drug dose requirements and in drug responses in the newborn. Pharmacogenomics is a tool that can be used to individualize drug therapy in newborns to minimize adverse drug effects and to optimize efficacy.
Kapur
Gaurav
G
Department of Pediatric Nephrology, Pediatric Pharmacology Research Unit Network, Wayne State University School of Medicine, Children's Hospital of Michigan, Detroit, MI 48201, USA.
Mattoo
Tej
T
Aranda
J V
JV
D000450:Aldosterone / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D007668:Kidney / Q000254:growth & development* / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010597:Pharmacogenetics; D010599:Pharmacokinetics; D011110:Polymorphism, Genetic; D011943:Receptors, Adrenergic, beta / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics
D002352:Carrier Proteins; D004364:Pharmaceutical Preparations; D011943:Receptors, Adrenergic, beta; D000450:Aldosterone