title: Pharmacokinetic and pharmacogenetic determinants and considerations in chemotherapy selection and dosing in infants.
abstract: BACKGROUND
  There is a lack of high-quality data regarding optimal chemotherapy dosage regimens among infants. Dosing regimens for chemotherapy during the first year of life are commonly based on empiric recommendations extrapolated from older children; however, balancing efficacy and toxicity is critical as severe adverse drug reactions may lead to treatment failure or reduced adherence to needed medications.
  
  
  METHODS
  This review describes pharmacokinetic and pharmacogenetic considerations when administering chemotherapeutic agents to infants. Examples of commonly used agents are provided with practical recommendations for dosing adjustments.
  
  
  CONCLUSIONS
  Optimal chemotherapy for children and infants in particular has lagged behind the remarkable progress in cancer treatment and it is clear that far more basic and clinical research are needed with respect to the mechanistic basis of age-dependent differences in pharmacokinetic parameters. More recent studies which have combined pharmacokinetic data with clinical toxicity and outcome data have resulted in a number of more evidence-based guidelines at least for the initial chemotherapy dosing; however, at present, the dosing of chemotherapy drugs in neonates and infants remains largely empiric.
authors.affiliation: University of Toronto, Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, 555 University Ave, Toronto ON, M5G 1X8, Canada.
authors.forename: Janine R
authors.initials: JR
authors.lastname: Hutson
authors.forename: Sheila
authors.initials: S
authors.lastname: Weitzman
authors.forename: Tal
authors.initials: T
authors.lastname: Schechter
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Arceci
authors.forename: Richard B
authors.initials: RB
authors.lastname: Kim
authors.forename: Yaron
authors.initials: Y
authors.lastname: Finkelstein
mesh_terms: D000367:Age Factors; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D001711:Biotransformation; D054796:Drug Dosage Calculations; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018579:Patient Selection; D010597:Pharmacogenetics; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D000970:Antineoplastic Agents