Studying Obesity and Drug Dosing in Children

Assessing the safety, efficacy, and dosing of acyclovir for the treatment of herpes simplex virus infections in infants using previously collected clinical data.

The pharmacokinetics of drugs commonly used in obese children can be markedly different from their lean peers. Most drugs are dosed using weight-based dosing guidelines; however, these guidelines may not be effective for obese children. This project will develop a drug database for clinicians and researchers that will provide dosing guidelines for obese children.

Kevin Watt, MD, of the Duke Clinical Research Institute, discusses the obesity informatics study.

Summary

Approximately one out of every five children in the United States is obese, a rate that has tripled since 1980. Obesity results in changes in body composition, physiology, and plasma protein binding—all of which have important implications for pharmacokinetics and drug dosing. For example, children who are obese often have different proportions of lean and fat body tissue, higher absorption, reduced therapeutic effects of drugs due to cardiac output, and altered renal elimination of drugs due to larger kidney size and renal blood flow.

Typical drug dosing guidelines based on patient weight may not be adequate for obese children because of altered body composition, physiology, and resulting changes in drug distribution. Depending on the physiochemical properties of a drug, using the “wrong” dose could limit the efficacy of the drug or place the child at increased risk of drug-related toxicity. Few clinical trials have examined the pharmacokinetics of drugs to inform safety, efficacy, or dosing guidelines for obese children.

The specific aims of this project are 1) to develop a user-friendly, drug database that provides specific dosing information for obese children; 2) to identify for the U.S. Food and Drug Administration major gaps in this knowledge base; and 3) to outline "next steps" protocols that address critical gaps in scientific and clinical practice needs for obese children.

Publications

Pharmacokinetics of antimicrobials in obese children.
Sampson MR, Cohen-Wolkowiez M, Benjamin DK Jr., Capparelli E, Watt KM, on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network.
Generics and Biosimilars Initiative Journal (GaBI Journal) • October 2013, volume 2, issue 2, pages 76-81.
PMCID: PMC4084753 [Free PMC article]

Drug dosing and pharmacokinetics in children with obesity: a systematic review.
Harskamp-van Ginkel MW, Hill KD, Becker K, Testoni D, Cohen-Wolkowiez M, Gonzalez D, Barrett JS, Benjamin DK Jr., Siegel DA, Banks P, Watt KM; for the Best Pharmaceuticals for Children Act–Pediatric Trials Network Administrative Core Committee.
JAMA Pediatrics • May 2015, volume 169, issue 7, pages 678-685.
PMCID: PMC4494887 [Free access available on 7/1/2016]

Gaps in Drug Dosing for Obese Children: A Systematic Review of Commonly Prescribed Emergency Care Medications.
Rowe S, Siegel D, Benjamin DK Jr; Best Pharmaceuticals for Children Act--Pediatric Trials Network Administrative Core Committee.
Clinical Therapy September 1, 2015, volume 39, issue 9, pages 1924-1932.
PMCID: PMC4586086 [Free access available on 9/1/2016]

Presentations

Pediatric Academic Societies Annual Meeting, May 4-7, 2013

Drug Dosing in Obese Children
Van Ginkel MW, Becker K, Cohen-Wolkowiez M, Smith PB, Barrett JS, Benjamin Jr., Watt KM

OVERVIEW

Status:
Published

Principal Investigators:
Christoph Hornick, MD, MPH and Kevin Watt, MD
Duke Health, Durham, NC

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