title: Exposure Matching of Pediatric Anti-infective Drugs: Review of Drugs Submitted to the Food and Drug Administration for Pediatric Approval.
abstract: Over the last decade, few new antibiotics have been approved by the Food and Drug Administration (FDA) for pediatric use. For most anti-infective agents, including antibiotics, extrapolation of efficacy from adults to children is possible if the disease and therapeutic exposures are similar between the 2 populations. This approach reduces the number of studies required in children, but relies heavily on exposure matching between children and adults. Failures in exposure matching can lead to delays in pediatric approvals of new anti-infective agents. We sought to determine the extent of exposure matching, defined by a comparison of area under the concentration-time curve, between children and adults, for anti-infective drug products submitted to the FDA for approval.
  
  
  
  We reviewed anti-infective submissions to the FDA (2002-2014) for pediatric indication. We included drug products administered via oral, intravenous, or intramuscular administration routes, and those with AUC estimates for children in available FDA reports. Our main outcome of interest was the proportion of drugs with median (or mean) pediatric AUC within 20% of the median (or mean) reported adult value.
  
  
  
  We identified 29 drug products that met inclusion criteria, 14 (48%) of which had mean (or median) AUCs of all submitted age groups within 20% of that in adults. Only route of administration and drug class were associated with pediatric AUC within 20% of adult AUC.
  
  
  
  Future research is needed to define criteria for and predictors of successful exposure matching of anti-infectives between children and adults.
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina; Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina.
authors.forename: Kanecia
authors.initials: K
authors.lastname: Zimmerman
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina.
authors.forename: Martin
authors.initials: M
authors.lastname: Putera
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina; Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina.
authors.forename: Christoph P
authors.initials: CP
authors.lastname: Hornik
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina; Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina.
authors.forename: P
authors.initials: P
authors.lastname: Brian Smith
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina; Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Benjamin
authors.affiliation: Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Yeruk
authors.initials: Y
authors.lastname: Mulugeta
authors.affiliation: Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Gilbert J
authors.initials: GJ
authors.lastname: Burckart
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina; Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina. Electronic address: michael.cohenwolkowiez@duke.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Cohen-Wolkowiez
authors.affiliation: Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina Eshelman School of Pharmacy, Chapel Hill, North Carolina.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gonzalez
mesh_terms: D000328:Adult; D000367:Age Factors; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002648:Child; D017277:Drug Approval / Q000379:methods*; D058492:Drug Repositioning / Q000379:methods; D006801:Humans; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000890:Anti-Infective Agents
keywords: anti-infectives; exposure matching; pediatrics; pharmacodynamics; pharmacokinetics