Infants

Rifampin Pharmacokinetics and Safety in Preterm and Term Infants

Posted on by Kayla Korzekwinski

Antimicrobial Agents and Chemotherapy • May 2019

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Smith PB, Cotten CM, Hudak ML, Sullivan JE, Poindexter BB, Cohen-Wolkowiez M, Boakye-Agyeman F, Lewandowski A, Anand R, Benjamin DK Jr, Laughon MM; Best Pharmaceuticals for Children Act—Pediatric Trials Network Steering Committee.

Rifampin is active against methicillin-resistant staphylococcal species and tuberculosis (TB). We performed a multicenter, prospective pharmacokinetic (PK) and safety study of intravenous rifampin in infants of <121 days postnatal age (PNA). We enrolled 27 infants; the median (range) gestational age was 26 weeks (23 to 41 weeks), and the median PNA was 10 days (0 to 84 days). We collected 102 plasma PK samples from 22 of the infants and analyzed safety data from all 27 infants. We analyzed the data using a population PK approach.

Surfactant Administration in Preterm Infants: Drug Development Opportunities

Posted on by Kayla Korzekwinski

The Journal of Pediatrics • May 2019

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Taylor G, Jackson W, Hornik CP, Koss A, Mantena S, Homsley K, Gattis B, Kudumu-Clavell M, Clark R, Smith PB, Laughon MM

This study evaluated how frequently surfactant is used off-label in preterm infants. The majority of surfactant given to preterm infants is administered off-label. The uptrend in administration via INSURE coincides with increased supporting evidence. The gap between FDA labeling and current clinic practice exemplifies an opportunity for label expansion, which may require additional prospective or retrospective safety and/or effectiveness data for infants of older GA and higher birth weight.

Pharmacokinetics of ticarcillin-clavulanate in premature infants

Posted on by Kayla Korzekwinski

British Journal of Clinical Pharmacology • May 2019

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Watt KM, Hornik CP, Balevic SJ, Mundakel G, Cotten CM, Harper B, Benjamin DK, Anand R, Laughon M, Smith PB, Cohen-Wolkowiez M; Best Pharmaceuticals for Children Act Pediatric Trials Network Steering Committee

Ticarcillin-clavulanate covers a broad spectrum of pathogens that are common in premature infants. In infants <30 weeks gestational age, pharmacokinetic data to guide ticarcillin-clavulanate dosing are lacking. This study enrolled premature infants <30 weeks gestational age, determined pharmacokinetic parameters, and performed dosing simulations to determine optimal dosing for ticarcillin-clavulanate.

Furosemide Exposure and Prevention of Bronchopulmonary Dysplasia in Premature Infants

Posted on by Kayla Korzekwinski

The Journal of Pediatrics • May 2019

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Greenberg RG, Gayam S, Savage D, Tong A, Gorham D, Sholomon A, Clark RH, Benjamin DK, Laughon M, Smith PB

The goal of this study was to evaluate the association between furosemide exposure and risk of bronchopulmonary dysplasia (BPD) for premature infants. More days of furosemide exposure between postnatal day 7 and 36 weeks was associated with decreased risk of BPD and a combined outcome of BPD or death.

Physiologically-Based Pharmacokinetic Modeling of Fluconazole Using Plasma and Cerebrospinal Fluid Samples From Preterm and Term Infants

Posted on by Kayla Korzekwinski

CPT: Pharmacometrics & Systems Pharmacology • May 2019

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Gerhart JG, Watt KM, Edginton A, Wade KC, Salerno SN, Benjamin DK, Smith PB, Hornik CP, Cohen-Wolkowiez M, Duara S, Ross A, Shattuck K, Stewart DL, Neu N, Gonzalez D, on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee

Fluconazole is used to treat hematogenous Candida meningoencephalitis in preterm and term infants. To characterize plasma and central nervous system exposure, an adult fluconazole physiologically-based pharmacokinetic (PBPK) model was scaled to infants, accounting for age dependencies in glomerular filtration and metabolism. Target attainment in plasma and CSF was reached faster after incorporating a loading dose of 25 mg/kg. PBPK modeling can be useful in exploring CNS kinetics of drugs in children.

Creation of a Multicenter Pediatric Inpatient Data Repository Derived from Electronic Health Records

Posted on by Kayla Korzekwinski

Applied Clinical Informatics Journal • March 2019

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Hornik CP, Atz AM, Bendel C, Chan F, Downes K, Grundmeier R, Fogel B, Gipson D, Laughon M, Miller M, Smith M, Livingston C, Kluchar C, Heath A, Jarrett C, McKerlie B, Patel H, Hunter C; Best Pharmaceuticals for Children Act Pediatric Trials Network

Integration of electronic health records (EHRs) data across sites and access to that data remain limited. This study developed an EHR-based pediatric inpatient repository using nine U.S. centers from the National Institute of Child Health and Human Development Pediatric Trials Network.

Sildenafil Exposure in the Neonatal Intensive Care Unit

Posted on by Kayla Korzekwinski

American Journal of Perinatology • February 2019

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Thompson EJ, Perez K, Hornik CP, Smith PB, Clark RH, Laughon M; Best Pharmaceuticals for Children Act—Pediatric Trials Network Steering Committee

Pulmonary hypertension causes substantial morbidity and mortality in infants. Although Food and Drug Administration approved to treat pulmonary arterial hypertension in adults, sildenafil is not approved for infants. This study sought to describe sildenafil exposure and associated diagnoses and outcomes in infants.

Systemic Timolol Exposure Following Topical Application to Infantile Hemangiomas

Posted on by Kayla Korzekwinski

Journal of the American Academy of Dermatology • February 2019

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Drolet BA, Boakye-Agyeman F, Harper B, Holland K, Lewandowski A, Stefanko N, Melloni C; Pediatric Trials Network Steering Committee.

Off-label ophthalmic timolol has been rapidly adopted for treatment of infantile hemangioma since topical application of beta-blockers was presumed to have an improved safety profile compared to oral administration. We examined timolol plasma concentrations in children receiving ophthalmic preparations applied to skin hemangiomas.

National Survey of Neonatal Intensive Care Unit Medication Safety Practices

Posted on by Kayla Korzekwinski

American Journal of Perinatology • November 2018

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Greenberg RG, Smith PB, Bose C, Clark RH, Cotten CM, DeRienzo C.

We conducted a detailed survey to identify medication safety practices among a large network of United States neonatal intensive care units (NICUs). We created a 53-question survey to assess 300 U.S. NICU’s demographics, medication safety practices, adverse drug event (ADE) reporting, and ADE response plans.

Association of Atrial Septal Defects and Bronchopulmonary Dysplasia in Premature Infants

Posted on by Kayla Korzekwinski

The Journal of Pediatrics • November 2018

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Kumar KR, Clark DA, Kim E, Perry JD, Wright K, Thomas SA, Thompson EJ, Greenberg RG, Smith PB, Benjamin DK, Laughon MM, Clark RH, Hornik CP

This study evaluated the association between the presence of an atrial septal defect (ASD) and the odds of developing bronchopulmonary dysplasia (BPD) in premature infants. The presence of an ASD was associated with an increased odds of BPD in this cohort. Future trials should consider ASD as a potentially modifiable risk factor in this vulnerable population.