Developmental pharmacology.
Understanding the pharmacokinetics and pharmacodynamics of drugs used in psychopharmacology across the pediatric age spectrum from infants to adolescents represents a major challenge for clinicians. In pediatrics, treatment protocols use either standard dose reductions for these drugs for children below a certain age or use less conventional parameters such as weight for allometric dosing. The rationale behind this, however, is often lacking. In this review current available data on the developmental changes in absorption, distribution, metabolism, and elimination of drugs are presented with a specific focus on metabolic pathways, indicating significant differences in the development of enzymes involved in the biotransformation of drugs used in psychopharmacology. Major emphasis will be given to the genetic variation in CYP2D6 activity, the most important enzyme for the metabolism of many psychotropic medications. Finally, this review will summarize the role of the developmental pharmacologist in ensuring rational use of drugs in children with developmental disabilities and in translating pharmacological concepts from the bench to the clinic.
van den Anker
Johannes N
JN
Division of Pediatric Clinical Pharmacology, George Washington University Medical Center, Children's National Medical Center, Washington DC, USA. jvandena@cnmc.org
D000293:Adolescent; D000367:Age Factors; D001682:Biological Availability; D002648:Child; D002675:Child, Preschool; D019389:Cytochrome P-450 CYP2D6 / Q000502:physiology; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D002658:Developmental Disabilities / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics; D004347:Drug Interactions; D016903:Drug Monitoring; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics / Q000502:physiology; D007223:Infant; D007408:Intestinal Absorption / Q000235:genetics / Q000502:physiology; D008657:Metabolic Clearance Rate / Q000235:genetics / Q000502:physiology; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic / Q000235:genetics; D011619:Psychotropic Drugs / Q000493:pharmacokinetics* / Q000627:therapeutic use*
D065690:Cytochrome P-450 CYP2D6 Inhibitors; D011619:Psychotropic Drugs; D019389:Cytochrome P-450 CYP2D6