Infants

Safety of sildenafil in extremely premature infants: a phase I trial

Posted on by Kayla Korzekwinski

Journal of Perinatology • January 2022

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Jackson W, Gonzalez D, Smith PB, Ambalavanan N, Atz A, Sokol GM, Hornik CD, Stewart D, Mundakel G, Poindexter BB, Ahlfeld SK, Mills M, Cohen-Wolkowiez M, Martz K, Hornik CP, Laughon MM; on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee
This study sought to characterize the safety of sildenafil in premature infants. Safety was evaluated based on adverse events (AEs), transaminase levels, and mean arterial pressure monitoring. There was one serious AE related to the study drug involving hypotension associated with a faster infusion rate than specified by the protocol. There were no AEs related to elevated transaminases. Sildenafil was well tolerated by the study population. Drug administration times and flush rates require careful attention to prevent infusion-related hypotension associated with faster infusions of IV sildenafil in premature infants.

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

Posted on by Kayla Korzekwinski

Antimicrobial Agents and Chemotherapy • June 2021

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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

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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.

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

Posted on by Kayla Korzekwinski

The Journal of Clinical Pharmacology • March 2021

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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

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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

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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

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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

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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

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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.