Hypertension

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.

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 sildenafil in extremely premature infants

Posted on by Kayla Korzekwinski

British Journal of Clinical Pharmacology • December 2019

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Gonzalez D, Laughon MM, Smith PB, Ge S, Ambalavanan N, Atz A, Sokol GM, Hornik CD, Stewart D, Mundakel G, Poindexter BB, Gaedigk R, Mills M, Cohen-Wolkowiez M, Martz K, Hornik CP

We performed a multicentre, open-label trial to characterize the pharmacokinetics (PK) of sildenafil in infants ≤28 weeks gestation and < 365 postnatal days (cohort 1) or < 32 weeks gestation and 3-42 postnatal days (cohort 2). We successfully characterized the PK of sildenafil and DMS in premature infants and applied the model to inform dosing for a follow-up, phase II study.

The use of supplemental hydrocortisone in the management of persistent pulmonary hypertension of the newborn

Posted on by Kayla Korzekwinski

Journal Perinatology • April 2021

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Aleem S, Robbins C, Murphy B, Elliott S, Akinyemi C, Paredes N, Tolia VN, Zimmerman KO, Goldberg RN, Benjamin DK, Greenberg RG

This study aimed to characterize the association between hydrocortisone receipt and hospital outcomes of infants with persistent pulmonary hypertension of the newborn (PPHN). There was no association between hydrocortisone receipt and death, CLD, or oxygen at discharge in our cohort. Prospective studies are needed to evaluate the effectiveness of hydrocortisone in infants with PPHN.

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.

Association between Furosemide Exposure and Patent Ductus Arteriosus in Hospitalized Infants of Very Low Birth Weight

Posted on by Kayla Korzekwinski

The Journal of Pediatrics • August 2018

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Thompson EJ, Greenberg RG, Kumar K, Laughon M, Smith PB, Clark RH, Crowell A, Shaw L, Harrison L, Scales G, Bell N, Hornik CP

This study evaluated the association between furosemide exposure and patent ductus arteriosus (PDA) in a large, contemporary cohort of hospitalized infants with very low birth weight (VLBW). Furosemide exposure was not associated with increased odds of PDA treatment in hospitalized infants of VLBW. Further studies are needed to characterize the efficacy and safety of furosemide in premature infants.

In-hospital outcomes of premature infants with severe bronchopulmonary dysplasia

Posted on by Kayla Korzekwinski

Journal of Perinatology • July 2017

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Jackson W, Hornik CP, Messina J, Guglielmo K, Watwe A, Delancy G, Valdez A, MacAuthur T, Peter-Wohl S, Smith PB, Clark R, Laughon MM

This study characterized in-hospital outcomes of premature infants diagnosed with severe bronchopulmonary dysplasia (BPD). A majority of infants diagnosed with severe BPD were discharged home by 44 weeks of postmenstrual age. These results may inform discussions with families regarding the expected hospital course of infants diagnosed with severe BPD.

Safety of Enalapril in Infants Admitted to the Neonatal Intensive Care Unit

Posted on by Kayla Korzekwinski

Pediatric Cardiology • January 2017

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Ku LC, Zimmerman K, Benjamin DK, Clark RH, Hornik CP, Smith PB; Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee.

Enalapril is used to treat hypertension and congestive heart failure in infants. However, enalapril is not labeled for neonates, and safety data in infants are sparse. To evaluate the safety of enalapril in young infants, we conducted a retrospective cohort study of infants who were exposed to enalapril in the first 120 days of life and were cared for in 348 neonatal intensive care units from 1997 to 2012.

Sildenafil and retinopathy of prematurity risk in very low birth weight infants

Posted on by Kayla Korzekwinski

American Journal of Perinatology • February 2016

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Samiee-Zafarghandy S, van den Anker JN, Laughon MM, Clark RH, Smith PB, Hornik CP; Pharmaceuticals for Children Act – Pediatric Trials Network Administrative Core Committee.

We identified premature infants who were discharged from Pediatrix Medical Group neonatal intensive care units from 2003–2012 and who received an ophthalmologic exam. We matched each infant exposed to sildenafil prior to first eye exam to three non-exposed infants using propensity scoring to control for differences in baseline infant characteristics. We evaluated the association between sildenafil exposure and development of severe ROP using conditional logistic regression.

Pharmacokinetics, Pharmacodynamics, and Safety of Lisinopril in Pediatric Kidney Transplant Patients: Implications for Starting Dose Selection

Posted on by Kayla Korzekwinski

Clinical Pharmacology Therapy • July 2015

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Trachtman H, Frymoyer A, Lewandowski A, Greenbaum LA, Feig DI, Gipson DS, Warady BA, Goebel JW, Schwartz GJ, Lewis K, Anand R, Patel UD; Best Pharmaceuticals for Children Act-Pediatric Trials Network Administrative Core Committee.

Hypertension in pediatric kidney transplant recipients contributes to long-term graft loss, yet treatment options–including angiotensin-converting enzyme inhibitors–are poorly characterized in this vulnerable population. We conducted a multicenter, open-label pharmacokinetic (PK) study of daily oral lisinopril in 22 children (ages 7-17 years) with stable kidney transplant function. Standard noncompartmental PK analyses were performed at steady state.