Obesity

Population Pharmacokinetic Modeling of Oxcarbazepine and Its Active Metabolite 10-Monohydroxy Derivative to Inform Dosing in Children with Obesity

Posted on by Jeannine Sato

Clinical Pharmacokinetics, November 2025

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Sinha J, Zimmerman K, Balevic SJ, Hornik C, Muller WJ, Rathore M, Meyer M, Finkelstein Y, Al-Uzri A, Lakhotia A, Goldstein S, Chen JY, Anand R, Gonzalez D; Best Pharmaceuticals for Children Act–Pediatric Trials Network Steering Committee.

Oxcarbazepine (OXZ) is an antiepileptic drug whose pharmacological effect is primarily mediated by its active metabolite, 10-monohydroxy derivative (MHD). OXZ is approved for use in adults and children older than 2 years with an age- and body weight-tiered dosing recommendation, but dosing guidance for children with obesity is lacking. This work aimed to assess the dosing requirements of OXZ in children with obesity to support label extension.

Physiologically Based Pharmacokinetic Modeling of Oxcarbazepine to Characterize Its Disposition in Children with Obesity

Posted on by Jeannine Sato

Journal of Clinical Pharmacology, September 2025

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Maglalang PD, Sinha J, Helfer VE, Edginton A, Zimmerman K, Hornik CD, Muller WJ, Rathore M, Benjamin DK Jr, Chen JY, Anand R, Gonzalez D; Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee. 

Oxcarbazepine (OXC) is a second-generation antiseizure medication, effective through its active metabolite, 10-mono-hydroxy derivative (MHD). OXC is used as adjunctive therapy for focal-onset and primary generalized tonic-clonic seizures, with recommended dosing based on age and body weight. This study uses physiologically based pharmacokinetic (PBPK) modeling and leverages pharmacokinetic (PK) data acquired from children enrolled in pragmatic trials to understand dosing and subsequent exposure requirements in children with obesity. 

Physiologically Based and Population Pharmacokinetic Modeling of Midazolam in Children With Obesity Using Real-World Data

Posted on by Jeannine Sato

Clinical and Translational Science, May 2025

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McCann S, Helfer VE, Balevic SJ, Muller WJ, van den Anker JN, Al-Uzri A, Meyer ML, Anderson SG, Turdalieva S, Edginton AN, Gonzalez D; Best Pharmaceuticals for Children Act Pediatric Trials Network Steering Committee.

Midazolam has been used as a sedative for hospitalized children on- and off-label; however, factors affecting interindividual variability (IIV) in observed clearance for this population are not fully understood and can result in extreme under- or overexposure. Obesity has been described as a significant influence on midazolam in adolescents, which could potentially alter drug exposure. The goal of this study was to use two modeling strategies to evaluate dose-exposure of midazolam in children with and without obesity. 

Expansion of a Pharmacokinetic Model for Diazepam to Characterize Real-World IV and Oral Data in Children With and Without Obesity

Posted on by Jeannine Sato

Journal of Clinical Pharmacology, April 2025

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McCann SM, Wen J, Balevic SJ, Muller WJ, Al-Uzri A, Hornik CD, Meyer ML, Anderson SG, Payne EH, Turdalieva S, Chamberlain JM, Gonzalez D; Best Pharmaceuticals for Children Act Pediatric Trials Network Steering Committee.

Diazepam is a benzodiazepine approved for use in adults and children. The label incorporates recommended dosing for status epilepticus in children. Published population pharmacokinetic (PK) modeling recommends an intravenous bolus dose of 0.2 mg/kg capped at 8 mg to reach the suggested target exposure of 200-600 ng/mL at 10 min post dose in children up to 17 years of age. This model was developed for children generally without obesity based on IV data, and it is unclear how increased body weight may affect exposure or target attainment given capped dosing.

Pharmacokinetics of Dexamethasone in Children and Adolescents with Obesity

Posted on by Kayla Korzekwinski

The Journal of Clinical Pharmacology • August 2024

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Wen J, McCann S, Balevic S, Muller WJ, Hornik C, Autmizguine J, Anderson SG, Payne EH, Turdalieva S, Gonzalez D., Best Pharmaceuticals for Children Act – Pediatric Trials Network

Dexamethasone is a synthetic glucocorticoid approved for treating disorders of various organ systems in both adult and pediatric populations. Currently, approved pediatric dosing recommendations are weight-based, but it is unknown whether differences in dexamethasone drug disposition and exposure exist for children with obesity. This study aimed to develop a population pharmacokinetic (PopPK) model for dexamethasone with data collected from children with obesity.

Physiologically-based pharmacokinetic modeling of pantoprazole to evaluate the role of CYP2C19 genetic variation and obesity in the pediatric population

Posted on by Kayla Korzekwinski

CPT: Pharmacometrics & Systems Pharmacology • August 2024

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Thompson EJ, Jeong A, Helfer VE, Shakhnovich V, Edginton A, Balevic SJ, James LP, Collier DN, Anand R, Gonzalez D., Best Pharmaceuticals for Children Act – Pediatric Trials Network

Pantoprazole is a proton pump inhibitor indicated for the treatment of gastroesophageal reflux disease, a condition that disproportionately affects children with obesity. Appropriately dosing pantoprazole in children with obesity requires understanding the body size metric that best guides dosing, but pharmacokinetic (PK) trials using traditional techniques are limited by the need for larger sample sizes and frequent blood sampling. This study explored the effect of obesity on pantoprazole PK and evaluated label-suggested dosing in this population.

Application of Physiologically Based Pharmacokinetic Modeling to Characterize the Effects of Age and Obesity on the Disposition of Levetiracetam in the Pediatric Population

Posted on by Kayla Korzekwinski

Clinical Pharmacokinetics • June 2024

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Maglalang PD, Sinha J, Zimmerman K, McCann S, Edginton A, Hornik CP, Hornik CD, Muller WJ, Al-Uzri A, Meyer M, Chen L, Anand R, Perrin E, Gonzalez D., Best Pharmaceuticals for Children Act–Pediatric Trials Network Steering Committee

Levetiracetam is an antiseizure medication used for several seizure types in adults and children aged 1 month and older; however, due to a lack of data, pharmacokinetic (PK) variability of levetiracetam is not adequately characterized in certain populations, particularly neonates, children younger than 2 years of age, and children older than 2 years of age with obesity. PBPK modeling simulations revealed that the current US FDA-labeled pediatric dosing regimen listed in the prescribing information can produce the required exposure of levetiracetam in these target populations with dose adjustments for children with obesity aged 4 years to younger than 16 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

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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.

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

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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.

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

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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.