title: Development of Human Membrane Transporters: Drug Disposition and Pharmacogenetics.
abstract: Membrane transporters play an essential role in the transport of endogenous and exogenous compounds, and consequently they mediate the uptake, distribution, and excretion of many drugs. The clinical relevance of transporters in drug disposition and their effect in adults have been shown in drug-drug interaction and pharmacogenomic studies. Little is known, however, about the ontogeny of human membrane transporters and their roles in pediatric pharmacotherapy. As they are involved in the transport of endogenous substrates, growth and development may be important determinants of their expression and activity. This review presents an overview of our current knowledge on human membrane transporters in pediatric drug disposition and effect. Existing pharmacokinetic and pharmacogenetic data on membrane substrate drugs frequently used in children are presented and related, where possible, to existing ex vivo data, providing a basis for developmental patterns for individual human membrane transporters. As data for individual transporters are currently still scarce, there is a striking information gap regarding the role of human membrane transporters in drug therapy in children.
authors.affiliation: Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, Room Sp-3458, Wytemaweg 80, PO-box 2060, 3000 CB, Rotterdam, The Netherlands.
authors.forename: Miriam G
authors.initials: MG
authors.lastname: Mooij
authors.affiliation: Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.|University of Tuebingen, Tuebingen, Germany.
authors.forename: Anne T
authors.initials: AT
authors.lastname: Nies
authors.affiliation: Faculty of Science, Leiden Academic Centre for Research, Pharmacology, Leiden, The Netherlands.|Hospital Pharmacy and Clinical Pharmacology, St. Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: Catherijne A J
authors.initials: CA
authors.lastname: Knibbe
authors.affiliation: Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.|University of Tuebingen, Tuebingen, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Schaeffeler
authors.affiliation: Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, Room Sp-3458, Wytemaweg 80, PO-box 2060, 3000 CB, Rotterdam, The Netherlands.
authors.forename: Dick
authors.initials: D
authors.lastname: Tibboel
authors.affiliation: Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.|Department of Clinical Pharmacology, University Hospital Tuebingen, Tuebingen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schwab
authors.affiliation: Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, Room Sp-3458, Wytemaweg 80, PO-box 2060, 3000 CB, Rotterdam, The Netherlands. s.dewildt@erasmusmc.nl.
authors.forename: Saskia N
authors.initials: SN
authors.lastname: de Wildt
mesh_terms: D000818:Animals; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010597:Pharmacogenetics; D010599:Pharmacokinetics
chemical_list: D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations