Pediatric Obesity: Pharmacokinetic Alterations and Effects on Antimicrobial Dosing

Authors

  • Stephanie Natale,

    1. Rady Children's Hospital, Departments of Infectious Diseases and Pharmacy Services, San Diego, CA
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  • John Bradley,

    1. Rady Children's Hospital, Departments of Infectious Diseases and Pharmacy Services, San Diego, CA
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  • William Huy Nguyen,

    1. Miller Children's and Women's Hospital and Long Beach Memorial Hospital, Department of Pharmacy Services, Long Beach, CA
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  • Tri Tran,

    1. Miller Children's and Women's Hospital and Long Beach Memorial Hospital, Department of Pharmacy Services, Long Beach, CA
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  • Pamela Ny,

    1. Miller Children's and Women's Hospital and Long Beach Memorial Hospital, Department of Pharmacy Services, Long Beach, CA
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  • Kirsten La,

    1. Miller Children's and Women's Hospital and Long Beach Memorial Hospital, Department of Pharmacy Services, Long Beach, CA
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  • Eva Vivian,

    1. University of Wisconsin MadisionSchool of Pharmacy, Madison, WI
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  • Jennifer Le

    Corresponding author
    1. Miller Children's and Women's Hospital and Long Beach Memorial Hospital, Department of Pharmacy Services, Long Beach, CA
    2. University of California San Diego, Skaggs School of Pharmacy and Pharmaceutical Sciences, La Jolla, CA
    • Address Correspondence to:

      Jennifer Le

      Professor of Clinical Pharmacy

      University of California San Diego

      Skaggs School of Pharmacy and Pharmaceutical Sciences

      9500 Gilman Drive, MC 0714

      La Jolla, CADrive, MC 071

      Phone: (858) 534-3692

      Fax: (858) 822-6857

      Email: jenle@ucsd.edu

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  • This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/phar.1899

Abstract

Background

Limited data exist for appropriate drug dosing in obese children. This comprehensive review summarizes pharmacokinetic alterations that occur with age and obesity, and these effects on antimicrobial dosing. A thorough comparison of different measures of body weight and specific antimicrobial agents, including cefazolin, cefepime, ceftazidime, daptomycin, doripenem, gentamicin, linezolid, meropenem, piperacill-tazobactam, tobramycin, vancomycin, and voriconazole, are presented.

Methods

PubMed (1966–July 2015) and Cochrane Library searches were performed using the following key terms—children, pharmacokinetic, obesity, overweight, body mass index, ideal body weight, lean body weight, body composition, and specific antimicrobial drugs. Pharmacokinetic studies in obese children and, if necessary, data from adult studies were summarized.

Results

Knowledge of pharmacokinetic alterations stemming from physiologic changes that occur with age from the neonate to adolescent, as well as those that result from increased body fat, become an essential first step towards optimizing drug dosing in obese children. Excessive amountsof adipose tissue contribute significantly to body size, total body water content, and organ size and function, which may modify drug distribution and clearance. Pharmacokinetic studies that evaluated antimicrobial dosing primarily used total (or actual) body weight (TBW) for loading doses and TBW or adjusted body weight (AdjBW) for maintenance doses, depending on the drugs’ properties and dosing units.

Conclusion

Pharmacokinetic studies in obese children are imperative to elucidate drug distribution, clearance, and, consequently, the dose required for effective therapy in these children. Future studies should evaluate the effects of both age and obesity on drug dosing as the incidence of obesity is increasing in pediatric patients.

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