Children (2-11 years)

Pharmacokinetics and Proposed Dosing of Levetiracetam in Children With Obesity

Posted on by Kayla Korzekwinski

The Journal of Pediatric Pharmacology and Therapeutics • December 2023

Access article on PubMed.

Zimmerman KO, Wu H, Maharaj A, Turner A, Chen L, Hornik CD, Arnold S, Muller W, Al-Uzri A, Meyer M, Shiloh-Malawsky Y, Taravath S, Lakhotia A, Joshi C, Jackman J, Hornik CP; on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network

This study sought to characterize levetiracetam pharmacokinetics (PK) in children with obesity to inform dosing. Weight-tiered dosing for levetiracetam oral solution and tablets for children with obesity 4 to <16 years old results in more comparable exposures to children of normal weight.

Impact of the COVID-19 Pandemic on Pediatric Preventive Health Care Among North Carolina Children Enrolled in Medicaid

Posted on by Kayla Korzekwinski

Journal of the Pediatric Infectious Diseases Society • December 2023

Access article on PubMed.

Thakkar PV, Scott Z, Hoffman M, Delarosa J, Hickerson J, Boutzoukas AE, Benjamin DK Jr., Brookhart MA, Zimmerman KO, Moorthy GS

This study used an administrative claims database from North Carolina Medicaid to evaluate the rates of well-child visits and immunization administration for children ≤14 months of age, and used a quasi-Poisson regression model to estimate the rate ratio of each outcome during the pandemic period (3/15/2020 through 3/15/2021) compared with the pre-pandemic period (3/15/2019 through 3/14/2020). The rates of well-child visits and immunization administrations among North Carolina children enrolled in public insurance substantially decreased during the first year of the COVID-19 pandemic.

Use of Real-World Data and Physiologically-Based Pharmacokinetic Modeling to Characterize Enoxaparin Disposition in Children With Obesity

Posted on by Kayla Korzekwinski

Clinical Pharmacology & Therapeutics • August 2022

Access article on PubMed.

Gerhart JG, Carreño FO, Loop MS, Lee CR, Edginton AN, Sinha J, Kumar KR, Kirkpatrick CM, Hornik CP, Gonzalez D; Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee
Dosing guidance for children with obesity is often unknown despite the fact that nearly 20% of US children are classified as obese. Enoxaparin, a commonly prescribed low-molecular-weight heparin, is dosed based on body weight irrespective of obesity status to achieve maximum concentration within a narrow therapeutic or prophylactic target range. However, whether children with and without obesity experience equivalent enoxaparin exposure remains unclear. The study aimed to answer this clinical question. Enoxaparin exposure was better matched across age groups and obesity status using fat-free mass weight-based dosing.

Extrapolation of Adult Efficacy Data to Pediatric Systemic Lupus Erythematosus: Evaluating Similarities in Exposure-Response

Posted on by Kayla Korzekwinski

Journal of Clinical Pharmacology • January 2023

Access article on PubMed.

Balevic SJ, Niu J, Chen J, Green D, McMahon A, Hornik CP, Schanberg L, Glaser R, Doddapaneni S, Gonzalez D, Burckart GJ

To streamline drug development, the United States Food and Drug Administration (FDA) can consider the extrapolation of adult efficacy data to children when the disease and drug effects are sufficiently similar. This study explored whether the relationship between drug exposure and response for selected drugs in systemic lupus erythematosus (SLE) was sufficiently similar to support a consideration of the extrapolation of adult efficacy data to children of ≥5 years of age.

Use of physiologically-based pharmacokinetic modeling to inform dosing of the opioid analgesics fentanyl and methadone in children with obesity

Posted on by Kayla Korzekwinski

CPT: Pharmacometrics & Systems Pharmacology • June 2022

Access article on PubMed.

Gerhart JG, Carreno FO, Ford JL, Edginton AN, Perrin EM, Watt KM, Muller WJ, Atz AM, Al-Uzri A, Delmore P, Gonzalez D; on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee
Children with obesity are commonly prescribed the opioids fentanyl and methadone, and accurate dosing is critical to reducing the risk of serious adverse events associated with overexposure. However, there is limited information to guide fentanyl and methadone dosing in these children. This study addresses the clinical knowledge gap using physiologically-based pharmacokinetic models of fentanyl and methadone developed in adults and scaled to children with and without obesity to explore the interplay of obesity, age, and pharmacogenomics.

External Evaluation of Risperidone Population Pharmacokinetic Models Using Opportunistic Pediatric Data

Posted on by Kayla Korzekwinski

Frontiers in Pharmacology • March 2022

Access article on PubMed.

Karatza E, Ganguly S, Hornik CD, Muller MJ, Al-Uzri A, James L, Balevic SJ, Gonzalez D; on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee
Risperidone is approved to treat schizophrenia in adolescents and autistic disorder and bipolar mania in children and adolescents. It is also used off-label in younger children for various psychiatric disorders. The objectives of this study were to assess whether opportunistically collected pediatric data can be used to evaluate risperidone population pharmacokinetic models externally and to identify a robust model for precision dosing in children. All the models had a modest predictive performance, potentially suggesting that sources of inter-individual variability were not entirely captured and that opportunistic data from a highly heterogeneous population are likely not the most appropriate data to evaluate risperidone models externally.

Development and Evaluation of a Virtual Population of Children with Obesity for Physiologically Based Pharmacokinetic Modeling

Posted on by Kayla Korzekwinski

Clinical Pharmacokinetics • February 2022

Access article on PubMed.

Gerhart JG, Carreno FO, Edginton AN, Sinha J, Perrin E, Kumar KR, Rikhi A, Hornik CP, Harris V, Ganguly S, Cohen-Wolkowiez M, Gonzalez D; on behalf of the Best Pharmaceuticals for Children Act — Pediatric Trials Network Steering Committee
A virtual population of children with obesity was developed using national survey, electronic health record, and clinical trial data, as well as data extracted from the literature. The objective of this study was to develop a virtual population of children with obesity to enable physiologically based pharmacokinetic modeling, then use the novel virtual population in conjunction with previously developed models of clindamycin and trimethoprim/sulfamethoxazole to better understand dosing of these drugs in children with obesity. Model simulations supported current recommended weight-based dosing in children with obesity for clindamycin and trimethoprim/sulfamethoxazole, as they met target exposure despite these changes in clearance and volume of distribution.

Impact of Personal Protective Equipment on the Performance of Emergency Pediatric Tasks

Posted on by Kayla Korzekwinski

Pediatric Emergency Care • December 2021

Access article on PubMed.

Adler MD, Krug S, Eiger C, Good GL, Kou M, Nash M, Henretig FM, Hornik CP, Gosnell L, Chen JY, Debski J, Sharma G, Siegel D, Donoghue A
This study evaluated the impacts of personal protective equipment (PPE) on timeliness or success of emergency procedures performed by pediatric health care providers (HCPs). For session 1, HCPs wore normal attire; for session 2, they wore full-shroud PPE garb with 2 glove types: Ebola level or chemical. During each session, they performed clinical tasks on a patient simulator: intubation, bag-valve mask ventilation, venous catheter (IV) placement, push-pull fluid bolus, and defibrillation. Personal protective equipment did not affect procedure timeliness or success on a simulated child, with the exception of IV placement. Further study is needed to investigate PPE’s impact on procedures performed in a clinical care context.

External Evaluation of Two Pediatric Population Pharmacokinetics Models of Oral Trimethoprim and Sulfamethoxazole

Posted on by Kayla Korzekwinski

Antimicrobial Agents and Chemotherapy • June 2021

Access article on PubMed.

Wu YSS, Cohen-Wolkowiez M, Hornik CP, Gerhart JG, Autmizguine J, Cobbaert M, Gonzalez D
This study tested the pediatric pharmacokinetics (PK) of the antibiotic combination trimethoprim (TMP)-sulfamethoxazole (SMX) that is used to treat a variety of infections. Both models used supported TMP-SMX dose increases in infants and young children for resistant pathogens with a MIC of 1 mg/liter, although the required dose increase based on the external model was lower.

Racial and Ethnic Diversity in Studies Funded Under the Best Pharmaceuticals for Children Act

Posted on by Kayla Korzekwinski

Pediatrics • May 2021

Access article on PubMed.

Abdel-Rahman SM, Paul IM, Hornik C, Sullivan JE, Wade K, Delmore P, Sharma G, Benjamin DK, Zimmerman KO

The Best Pharmaceuticals for Children Act (BPCA) incentivizes the study of on-patent medicines in children and mandates that the NIH sponsor research on off-patent drugs important to pediatric therapeutics. Failing to enroll cohorts that reflect the pediatric population at large restricts the generalizability of such studies. This investigation evaluates racial and ethnic minority representation among participants enrolled in BPCA-sponsored studies. This study revealed no evidence of racial and ethnic bias in enrollment for pediatric studies conducted with funding from BPCA, fulfilling the legislation’s expectation to ensure adequate representation of all children.