Study Population

Pharmacoepidemiology of combination pulmonary vasodilator therapy in critically ill infants

Posted on by Kayla Korzekwinski

Cardiology in the Young • January 2025

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Kumar KR, Ciociola EC, Skinner KR, Dixit GM, Alvarez S, Benjamin EK, Faulkner JC, Greenberg RG, Clark RH, Benjamin Jr DK, Hornik CP and Jan Hau Lee

New drugs to target different pathways in pulmonary hypertension have resulted in increased combination therapy, but details of this use in infants are not well described. This large multicenter database study describes the pharmacoepidemiology of combination pulmonary vasodilator therapy in critically ill infants. The study revealed an increased use of combination pulmonary vasodilator therapy, favouring inhaled nitric oxide and sildenafil, yet with considerable practice variation. Further research is needed to determine the optimal combination, sequence, dosing, and disease-specific indications for combination therapy.

Trends in Gabapentin Use in Neonatal Intensive Care Units from 2005 to 2020

Posted on by Kayla Korzekwinski

American Journal of Perinatology • November 2024

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Roberts AG, Kilpatrick R, Diaz LD, Benjamin S, Espinoza Santiago AJ, Jallow B, Monteith MF, Rumsey S, Clark RH, Zimmerman K, Benjamin DK Jr, Greenberg RG

This study aimed to analyze trends in gabapentin use in neonatal intensive care units (NICUs) and examine demographic characteristics, diagnoses, and concomitant medications associated with its use. Gabapentin use was rare but increased over time despite limited research on its safety and efficacy in infants, illuminating the need for further studies.

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.

Using Real-World Data to Externally Evaluate Population Pharmacokinetic Models of Dexmedetomidine in Children and Infants

Posted on by Kayla Korzekwinski

The Journal of Clinical Pharmacology • August 2024

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McCann S, Helfer VE, Balevic SJ, Hornik CH, Goldstein SL, Autmizguine J, Meyer M, Al-Uzri A, Anderson SG, Payne EH, Turdalieva S, Gonzalez D., Best Pharmaceuticals for Children Act – Pediatric Trials Network

Dexmedetomidine is a sedative used in both adults and off-label in children with considerable reported pharmacokinetic (PK) interindividual variability affecting drug exposure across populations. Several published models describe the population PKs of dexmedetomidine in neonates, infants, children, and adolescents, though very few have been externally evaluated. A prospective PK dataset of dexmedetomidine plasma concentrations in children and young adults aged 0.01-19.9 years was collected as part of a multicenter opportunistic PK study.

Epidemiology and outcomes of bacterial meningitis in the neonatal intensive care unit

Posted on by Kayla Korzekwinski

Journal of Perinatology • July 2024

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Aleem S, Benjamin DK Jr, Burns C, Duncan J, Melaku K, Norbekov A, Graham B, Mantena S, Ladipo T, Jung A, Zimmerman KO, Clark RH, Greenberg RG

This study examined pathogen distribution, antibiotic resistance patterns, and hospital outcomes of infants with bacterial meningitis in neonatal intensive care units (NICUs) in the US from 2013-2018.

Acyclovir Dosing Practices Across a Multicenter Cohort of Neonatal Intensive Care Units

Posted on by Kayla Korzekwinski

The Pediatric Infectious Disease Journal • June 2024

Foote HP, Thomassy H, Baquero L, Cayli M, Jacobs E, Paladugu A, Roy A, Heyward E, Clark RH, Hornik CP, Benjamin DK, Benjamin DK Jr, Greenberg RG

Acyclovir is the first-line therapy for neonatal herpes simplex virus infections. Therapy can mitigate morbidity and mortality but carries a risk for toxicity. This study aimed to compare acyclovir dosing in neonatal intensive care units to published recommendations based on population pharmacokinetic (PopPK) analysis.

Postdiscontinuation Antibiotic Exposure in Hospitalized Infants at Risk for Late-onset Sepsis in the Neonatal Intensive Care Unit

Posted on by Kayla Korzekwinski

The Pediatric Infectious Disease Journal • June 2024

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Wade KC, Greenberg RG, Benjamin DK Jr., Chen L, Vo B, Ang BL, Boutzoukas A, Zimmerman KO, Clark RH, Cohen-Wolkowiez M, Le J on behalf of the Administrative Core Committee of the Best Pharmaceuticals for Children Act – Pediatric Trials Network

In the neonatal intensive care unit, infants are at risk for late-onset sepsis. When blood cultures are negative, antibiotic stewardship efforts encourage stopping antibiotics, yet the duration of therapeutic exposure after the last dose is unknown. Piperacillin and cefepime exposures remained therapeutic long after the expected 8- to 12-hour dosing interval. PDAE is an important consideration for antibiotic stewardship among hospitalized infants, particularly premature infants and those within 1 month postbirth.

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.

Urinary Tract Infection Epidemiology in NICUs in the United States

Posted on by Kayla Korzekwinski

American Journal of Perinatology • May 2024

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Kilpatrick R, Boutzoukas AE, Chan E, Girgis V, Kinduelo V, Kwabia SA, Yan J, Clark RH, Zimmerman KO, Greenberg RG

This study characterized the incidence, associated clinical factors, timing of infection, microbiology, and incidence of concordant blood culture of urinary tract infections (UTIs) in very low birth weight (VLBW <1,500g) infants. UTI is a common cause of infection in VLBW infants, especially among the smallest, most premature, male infants, and those with a longer duration of hospitalization. Neonatal clinicians should consider obtaining urine culture in the setting of late-onset sepsis evaluations in VLBW infants.