A Population-Based Pharmacokinetic Model Approach to Pantoprazole Dosing for Obese Children and Adolescents

Pediatric Drugs • October 2018.

Shakhnovich V, Brian Smith P, Guptill JT, James LP, Collier DN, Wu H, Livingston CE, Zhao J, Kearns GL, Cohen-Wolkowiez M; Best Pharmaceuticals for Children Act–Pediatric Trials Network.

Pharmacokinetic data for proton pump inhibitors (PPIs), acid-suppression drugs commonly prescribed to children, are lacking for obese children who are at greatest risk for acid-related disease. In a recent multi-center investigation, we demonstrated decreased, total body weight adjusted, apparent clearance (CL/F) of the PPI pantoprazole for obese children compared with their non-obese peers.

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Obese Children Require Lower Doses of Pantoprazole Than Nonobese Peers to Achieve Equal Systemic Drug Exposures

The Journal of Pediatrics • February 2018.

Shakhnovich V, Smith PB, Guptill JT, James LP, Collier DN, Wu H, Livingston CE, Zhao J, Kearns GL; Best Pharmaceuticals for Children Act – Pediatric Trials Network.

To assess appropriate pantoprazole dosing for obese children, we conducted a prospective pharmacokinetics (PK) investigation of pantoprazole in obese children, a patient population that is traditionally excluded from clinical trials. A total of 41 obese children (6-17 years of age), genotyped for CYP2C19 variants *2, *3, *4, and *17, received a single oral dose of pantoprazole, ~1.2 mg/kg lean body weight (LBW), with LBW calculated via a validated formula.

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Pharmacokinetics of Clindamycin in Obese and Nonobese Children

Antimicrobial Agents and Chemotherapy • March 2017.

Smith MJ, Gonzalez D, Goldman JL, Yogev R, Sullivan JE, Reed MD, Anand R, Martz K, Berezny K, Benjamin DK Jr, Smith PB, Cohen-Wolkowiez M, Watt K; Best Pharmaceuticals for Children Act—Pediatric Trials Network Steering Committee.

Although obesity is prevalent among children in the United States, pharmacokinetic (PK) data for obese children are limited. Clindamycin is a commonly used antibiotic that may require dose adjustment in obese children due to its lipophilic properties. We performed a clindamycin population PK analysis using data from three separate trials. A total of 420 samples from 220 children, 76 of whom had a body mass index greater than or equal to the 95th percentile for age, were included in the analysis. Compared to other metrics, total body weight (TBW) was the most robust measure of body size.

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Gaps in Drug Dosing for Obese Children: A Systematic Review of Commonly Prescribed Emergency Care Medications

Clinical Therapy • September 2015.

Rowe S, Siegel D, Benjamin DK Jr; Best Pharmaceuticals for Children Act – Pediatric Trials Network Administrative Core Committee.

Approximately 1 of 6 children in the United States is obese. This has important implications for drug dosing and safety because pharmacokinetic (PK) changes are known to occur in obesity due to altered body composition and physiologic mechanisms. Inappropriate drug dosing in an emergency setting can limit therapeutic efficacy and increase drug-related toxic effects for obese children.

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Drug Dosing and Pharmacokinetics in Children With Obesity: A Systematic Review

JAMA Peds • July 2015.

Harskamp-van Ginkel MW, Hill KD, Becker KC, Testoni D, Cohen-Wolkowiez M, Gonzalez D, Barrett JS, Benjamin DK Jr, Siegel DA, Banks P, Watt KM; Best Pharmaceuticals for Children Act–Pediatric Trials Network Administrative Core Committee.

Obesity affects nearly one-sixth of US children and results in alterations to body composition and physiology that can affect drug disposition, possibly leading to therapeutic failure or toxic side effects. The depth of available literature regarding obesity’s effect on drug safety, pharmacokinetics, and dosing in obese children is unknown.

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Pharmacokinetics of Antimicrobials in Obese Children

GaBI Journal • June 2014.

Sampson M, Cohen-Wolkowiez M, Benjamin D Jr, Capparelli E, Watt K.

Childhood obesity is common and results in substantial morbidity. The most commonly prescribed drugs in obese children are antibiotics. However, physiological changes associated with childhood obesity can alter antibiotic pharmacokinetics and optimal body size measures to guide dosing in this population are ill defined. This combination can result in therapeutic failures or drug-related toxicities. This review summarizes pharmacokinetic information for antibiotics in obese children and implications for dosing.

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