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

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• 作者：Kanecia Zimmerman ; MD ; MPH¹ ; ² ; Martin Putera ; MD¹ ; Christoph P. Hornik ; MD ; MPH¹ ; ² ; P. Brian Smith ; MD ; MPH ; MHS¹ ; ² ; Daniel K. Benjamin Jr ; MD ; PhD ; MPH¹ ; ² ; Yeruk Mulugeta ; PharmD³ ; Gilbert J. Burckart ; PharmD³ ; Michael Cohen-Wolkowiez ; MD ; PhD¹ ; ² ; ^{michael.cohenwolkowiez@duke.edu" class="auth_mail" title="E-mail the corresponding author} ; Daniel Gonzalez ; PharmD ; PhD⁴
• 关键词：anti-infectives ; exposure matching ; pediatrics ; pharmacodynamics ; pharmacokinetics
• 刊名：Clinical Therapeutics
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：38
• 期：9
• 页码：1995-2005
• 全文大小：279 K

文摘

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.