Publications

Estimation of Body Fat Percentage for Clinical Pharmacokinetic Studies in Children

Posted on by Kayla Korzekwinski

Clinical and Translational Science • March 2021

Green TP, Binns HJ, Wu H, Ariza AJ, Perrin EM, Quadri M, Hornik CP, Cohen-Wolkowiez M

Obesity is a prevalent childhood condition and the degree of adiposity is likely to be an important covariate in the pharmacokinetics (PKs) of many drugs. The goal of these studies was to facilitate the evaluation and, where appropriate, quantification of the covariate effect of body fat percentage (BF%) on PK parameters in children. Researchers examined two large databases to determine the values and variabilities of BF% in children with healthy body weights and in those with obesity, comparing the accuracy and precision of BF% estimation by both clinical methods and demographically derived techniques. They also conducted simulation studies to evaluate the utility of the several methods for application in clinical trials. The estimation of BF% from sex and obesity stage can routinely be applied to PK clinical trials to evaluate the contribution of BF% as a potential covariate.

 

Pharmacokinetics of Hydrochlorothiazide in Children: A Potential Surrogate for Renal Secretion Maturation

Posted on by Kayla Korzekwinski

The Journal of Clinical Pharmacology • March 2021

Commander SJ, Wu H, Boakye-Agyeman F, Melloni C, Hornik CD, Zimmerman K, Al-Uzri A, Mendley SR, Harper B, Cohen-Wolkowiez M, Hornik CP
Hydrochlorothiazide (HCTZ) is a thiazide diuretic used in adults and children for the treatment of hypertension and edema. The pharmacokinetic (PK) properties of HCTZ in children are not well characterized, particularly among children with obesity who frequently suffer from hypertension and may, therefore, benefit from HCTZ therapy. Simulated exposure decreased with age and was likely due to older children receiving the maximum absolute doses of HCTZ. Further studies with more patients in each age group are required to confirm these PK findings of HCTZ in the children.

Population Pharmacokinetics of Olanzapine in Children

Posted on by Kayla Korzekwinski
British Journal of Clinical Pharmacology • February 2021
Maharaj AR, Wu H, Zimmerman KO, Autmizguine J, Kalra R, Al-Uzri A, Sherwin CMT, Goldstein SL, Watt K, Cohen-Wolkowiez M, Hornik CP; on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee
The aim of this study was to evaluate the population pharmacokinetics (PopPK) of olanzapine in children and devise a model-informed pediatric dosing scheme. This analysis is the first study to characterize the PK of olanzapine in participants ranging from infants to adolescents. Body weight and postmenstrual age (PMA) were identified as influential covariates for characterizing developmental changes in olanzapine apparent clearance.

Physiologically-Based Pharmacokinetic Modeling Characterizes the CYP3A-Mediated Drug-Drug Interaction Between Fluconazole and Sildenafil in Infants

Posted on by Kayla Korzekwinski

Clinical Pharmacology & Therapeutics • January 2021

Salerno SN, Edginton A, Gerhart JG, Laughon MM, Ambalavanan N, Sokol GM, Hornik CD, Stewart D, Mills M, Martz K, Gonzalez D; on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee
Infants being treated for pulmonary hypertension and prevention or treatment of invasive candidiasis may be given sildenafil with fluconazole concurrently. Physiologically-based pharmacokinetic (PBPK) modeling can potentially predict pediatric drug-drug interactions (DDIs) when clinical DDI data are limited. This study highlights the feasibility of PBPK modeling to predict DDIs in infants and the need to include CYP3A7 parameters.

Early-onset sepsis in term infants admitted to neonatal intensive care units (2011-2016)

Posted on by Kayla Korzekwinski

Journal of Perinatology • January 2021

Bech Polcwiartek L, Smith PB, Benjamin DK, Zimmerman KO, Love A, Tiu L, Murray S, Kang P, Ebbesen F, Hagstrøm S, Clark RH, Greenberg RG

This study investigated characteristics of term infants culture-evaluated for early-onset sepsis (EOS) in neonatal intensive care units (NICUs), frequencies of organisms causing EOS, and factors associated with EOS. EOS was most commonly caused by group B Streptococcus. Lower EOS risk was associated with low Apgar score, Cesarean delivery, small for gestational age, prenatal antibiotic exposure, and positive or unknown maternal GBS screening result. Increased risk was associated with prolonged rupture of membranes, maternal age <19 years, vasopressor treatment, and ventilator support.

Population Pharmacokinetics of Metoclopramide in Infants, Children, and Adolescents

Posted on by Kayla Korzekwinski

Clinical and Translational Science • November 2020

Ge S, Mendley SR, Gerhart JG, Melloni C, Hornik CP, Sullivan JE, Atz A, Delmore P, Tremoulet A, Poindexter BB, Harper B, Payne E, Lin S, Erinjeri J, Cohen-Wolkowiez M, Gonzalez D

Metoclopramide is commonly used for gastroesophageal reflux. The aims of the present study were to develop a pediatric population pharmacokinetic (PopPK) model, which was applied to simulate the metoclopramide exposure following dosing used in clinical practice. The study suggests that a metoclopramide dose as previously recommended for pediatric patients results in simulated exposure generally within suggested ranges for the treatment of gastroesophageal reflux.

Simulated Assessment of Pharmacokinetically Guided Dosing for Investigational Treatments of Pediatric Patients With Coronavirus Disease 2019

Posted on by Kayla Korzekwinski

JAMA Pediatrics • October 2020

Maharaj A, Wu H, Hornik CP, Balevic SJ, Hornik CD, Smith PB, Gonzalez D, Zimmerman KO, Benjamin DK Jr., Cohen-Wolkowiez M
This study sought to define pediatric-specific dosing regimens for hydroxychloroquine and remdesivir for COVID-19 treatment. Pharmacokinetic modeling and simulation were used to extrapolate investigated adult dosages toward children (March 2020-April 2020).  Concerns were raised regarding hydroxychloroquine use for COVID-19 treatment because concentrations were less than those needed to mediate an antiviral effect.

Exchange transfusion safety and outcomes in neonatal hyperbilirubinemia

Posted on by Kayla Korzekwinski

Pediatric Emergency Care • October 2020

Wolf MF, Childers J, Gray KD, Chivily C, Glenn M, Jones L, Kpa M, McMannen T, Reyes I, Zimmerman KO, Clark RH, Greenberg RG

This study aimed to characterize the prevalence of exchange transfusion (ET), clinical characteristics of infants receiving ET, and ET-associated morbidity and mortality. It was a multicenter cohort study of infants ≥23 weeks of gestational age (GA) with hyperbilirubinemia who underwent ET within 30 days of birth from 1997 to 2016. Infants ≤ 29 weeks of GA had greater odds of death following ET compared with term infants. These data will support clinicians in evaluating risks and prognosis for infants who require ET.

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Safety of Metronidazole in Late Preterm and Term Infants With Complicated Intraabdominal Infections

Posted on by Kayla Korzekwinski

Pediatric Infectious Disease Journal • September 2020

Commander SJ, Gao J, Zinkhan EK, Heresi G, Courtney SE, Lavery AP, Delmore P, Sokol GM, Moya F, Benjamin DK Jr, Bumpass TG, Debski J, Erinjeri J, Sharma G, Tracy ET, Cohen-Wolkowiez M, Hornik CP; on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee

Metronidazole is frequently used off-label in infants with complicated intra-abdominal infections (cIAI) to provide coverage against anaerobic organisms, but its safety and efficacy in this indication are unknown. Metronidazole safety was evaluated by reporting of adverse events (AEs) and safety events of special interest. In a cohort of late pre-term and term infants with cIAIs, combination antibiotic therapy that included metronidazole was safe, and therapeutic success was high.

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Hospital-acquired Pneumonia and Ventilator-associated Pneumonia in Children: A Prospective Natural History and Case-Control Study

Posted on by Kayla Korzekwinski

Pediatric Infectious Disease Journal • August 2020

Ericson JE, McGuire J, Michaels MG, Schwarz A, Frenck R, Deville JG, Agarwal S, Bressler AM, Gao J, Spears T, Benjamin DK, Smith PB, Bradley, JS

We examined laboratory and clinical features that might improve pediatric hospital-acquired and ventilator-associated bacterial pneumonias (HABP/VABP) trial efficiency by identifying risk factors predisposing children to HABP/VABP and describing the epidemiology of pediatric HABP/VABP. Food and Drug Administration-defined HABP/VABP occurred in 10%-12% of pediatric patients admitted to ICUs. Risk factors vary by age group.

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