Exposure Matching of Pediatric Anti-infective Drugs: Review of Drugs Submitted to the Food and Drug Administration for Pediatric Approval.

Journal Article (Journal Article;Review)

PURPOSE: 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. METHODS: 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. FINDINGS: 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. IMPLICATIONS: Future research is needed to define criteria for and predictors of successful exposure matching of anti-infectives between children and adults.

Full Text

Duke Authors

Cited Authors

  • Zimmerman, K; Putera, M; Hornik, CP; Brian Smith, P; Benjamin, DK; Mulugeta, Y; Burckart, GJ; Cohen-Wolkowiez, M; Gonzalez, D

Published Date

  • September 2016

Published In

Volume / Issue

  • 38 / 9

Start / End Page

  • 1995 - 2005

PubMed ID

  • 27364807

Pubmed Central ID

  • PMC5039072

Electronic International Standard Serial Number (EISSN)

  • 1879-114X

Digital Object Identifier (DOI)

  • 10.1016/j.clinthera.2016.06.003


  • eng

Conference Location

  • United States