Study Population

Population Pharmacokinetics of Milrinone in Infants, Children, and Adolescents

Posted on by Kayla Korzekwinski

Journal of Clinical Pharmacology • December 2019

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Hornik CP, Yogev R, Mourani PM, Watt KM, Sullivan JE, Atz AM, Speicher D, Al-Uzri A, Adu-Darko M, Payne E, Gelber C, Lin S, Harper B, Melloni C, Cohen-Wolkowiez M, Gonzalez D

Milrinone is a type 3 phosphodiesterase inhibitor used to improve cardiac output in critically ill infants and children. Milrinone is primarily excreted unchanged in the urine, raising concerns for toxic accumulation in the setting of renal dysfunction of critical illness. We developed a population pharmacokinetic model of milrinone using nonlinear mixed-effects modeling in NONMEM to perform dose-exposure simulations in children with variable renal function. Children below 21 years of age were included.

Population Pharmacokinetics of Doxycycline in Children

Posted on by Kayla Korzekwinski

Antimicrobial Agents and Chemotherapy • September 2019

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Thompson EJ, Wu H, Melloni C, Balevic S, Sullivan JE, Laughon M, Clark KM, Kalra R, Mendley S, Payne E, Erinjeri J, Gelber C, Harper B, Cohen-Wolkoweiz M, Hornik CP

Doxycycline is a tetracycline-class antimicrobial labeled by the United States (U.S.) Food and Drug Administration for children >8 years of age for many common childhood infections. Doxycycline is not labeled for children ≤8 years of age, due to the association between tetracycline class antibiotics and tooth staining. We leveraged opportunistically-collected plasma samples after intravenous (IV) and oral doxycycline doses received per standard of care to characterize the pharmacokinetics (PK) of doxycycline in children of different ages between 0 and 18 years.

Risk of Development of Treated Retinopathy of Prematurity in Very Low Birth Weight Infants

Posted on by Kayla Korzekwinski

Journal of Perinatology • September 2019

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Gonski S, Hupp S, Cotton CM, Clark R, Laughon M, Watt K, Hornik CP, Smith PB, Greenberg RG

Aim to quantify the risk of treatment for retinopathy of prematurity (ROP) among infants meeting current U.S. screening guidelines. Among infants ≤1500 g birth weight or ≤30 weeks gestation screened for ROP from 2006-2015, we developed a risk prediction model to identify infants treated for ROP. Applied to 6,127 infants discharged in 2016, our model had 97.9% sensitivity, 63.3% specificity, positive predictive value of 4.0%, and negative predictive value of 99.9%. Large numbers of infants at low risk of developing ROP are required to undergo screening. Refining current ROP guidelines may reduce unnecessary examinations.

Dosing and Safety of Off-label Use of Caffeine Citrate in Premature Infants

Posted on by Kayla Korzekwinski

Journal of Pediatrics • August 2019

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Puia-Dumitrescu M, Smith PB, Zhao J, Soriano A, Payne EH, Harper B, Bendel-Stenzel E, Moya F, Chhabra R, Ku L, Laughon M, Wade KC

Aim to characterize the dosing and safety of off-label caffeine citrate in a contemporary cohort of extremely premature infants. We used electronic health records (2010-2013) from 4 neonatal intensive care units to identify infants of ≤28 weeks of gestational age exposed to caffeine citrate. Of 410 infants with a median (IQR) gestational age of 26 (24-27) weeks, 95% received caffeine citrate for >0 days. Infants received a median (IQR) daily dose of 8 (5-10) mg/kg/day. Incidences of clinical events on day of caffeine citrate exposure were death 2%, patent ductus arteriosus ligation 12%, and medical and surgical necrotizing enterocolitis 5% and 4%, respectively.

Development of a Generic Physiologically-Based Pharmacokinetic Model for Lactation and Prediction of Maternal and Infant Exposure to Ondansetron via Breast Milk

Posted on by Kayla Korzekwinski

Clinical Pharmacology & Therapeutics • May 2022

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Job KM, Dallmann A, Parry S, Saade G, Haas D, Hughes B, Berens P, Chen JY, Fu C, Humphrey K, Hornik C, Balevic S, Zimmerman K, Watt K

Ondansetron is commonly used in breastfeeding mothers to treat nausea and vomiting. There is limited information in humans regarding safety of ondansetron exposure to nursing infants and no adequate study looking at ondansetron pharmacokinetics during lactation. This study developed a generic physiologically-based pharmacokinetic lactation model for small molecule drugs and applied this model to predict ondansetron transfer into breast milk and characterize infant exposure.

Medication Use in the Neonatal Intensive Care Unit and Changes from 2010 to 2018

Posted on by Kayla Korzekwinski

The Journal of Pediatrics • January 2022

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Stark A, Smith PB, Hornik CP, Zimmerman KO, Hornik CD, Pradeep S, Clark RH, Benjamin DK, Laughon M, Greenberg RG.

The goal of this study was to provide up-to-date medication prescribing patterns in US neonatal intensive care units (NICUs) and to examine trends in prescribing patterns over time. The most frequently prescribed medications included ampicillin, gentamicin, caffeine citrate, poractant alfa, morphine, vancomycin, furosemide, fentanyl, midazolam, and acetaminophen. Of the top 50 medications used in infants with extremely low birth weight, only 20 (40%) are FDA-labeled for use in infants. Trends of medication use in the NICU change substantially over time. It is imperative to identify changes in medication use in the NICU to better inform further prospective studies.

Low Etanercept Concentrations in Children With Obesity and Juvenile Idiopathic Arthritis

Posted on by Kayla Korzekwinski

The Journal of Pediatric Pharmacology and Therapeutics • November 2021

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Balevic SJ, Becker ML, Gonzalez D, Funk RS

This study evaluated the impact of obesity on etanercept (ETN) drug exposure in children with juvenile idiopathic arthritis (JIA). The data suggest that children who are obese may be routinely under-dosed using current dosing strategies. As a result, characterizing adequate drug exposure in children of all sizes is an important step toward precision dosing.

Comparative efficacy and safety of late surfactant preparations: a retrospective study

Posted on by Kayla Korzekwinski

Journal of Perinatology • November 2021

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Lane MD, Kishnani S, Udemadu O, Danquah SE, Treadway RM, Langman A, Balevic S, Jackson WM, Laughon M, Hornik CP, Greenberg RG, Clark RH, Zimmerman KO

This study sought to characterize the use, efficacy, and safety of poractant alfa and calfactant surfactants compared to beractant in preterm infants receiving late surfactant. Compared to beractant, there is no evidence of overall superior efficacy or safety of poractant alfa.

Pharmacokinetics of Ceftazidime in Children and Adolescents with Obesity

Posted on by Kayla Korzekwinski

Paediatric Drugs • September 2021

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Maharaj AR, Wu H, Zimmerman KO, Muller WJ, Sullivan JE, Sherwin CMT, Autmizguine J, Rathore MH, Hornik CD, Al-Uzri A, Payne EH, Hornik CP, on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee

The aim of this study was to evaluate ceftazidime pharmacokinetics (PK) in a cohort that includes a predominate number of children and adolescents with obesity and assess the efficacy of competing dosing strategies.

Physiologically Based Pharmacokinetic (PBPK) Modeling of Meropenem in Preterm and Term Infants

Posted on by Kayla Korzekwinski

Clinical Pharmacokinetics • June 2021

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Ganguly S, Edginton A, Gerhart JG, Cohen-Wolkowiez M, Greenberg RG, Gonzalez D; on behalf of the Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committee
This study applied physiologically based pharmacokinetic (PBPK) modeling to characterize the disposition of the antibiotic meropenem in preterm and term infants. Meropenem is approved by the US Food and Drug Administration for use in pediatric patients, including treating complicated intra-abdominal infections in infants < 3 months of age. The PBPK model-based simulations were performed to evaluate meropenem dosing in the product label for infants < 3 months of age treated for complicated intra-abdominal infections. The PBPK model used supports the meropenem dosing regimens recommended in the product label for infants <3 months of age.