ArticleBritish journal of clinical pharmacology2019
Population pharmacokinetics of sildenafil in extremely premature infants.
Article in British journal of clinical pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04447989 (Safety of Sildenafil in Premature Infants With Severe Bronchopulmonary Dysplasia), which is not on this map. Cited by 12 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Safety of Sildenafil in Premature Infants With Severe Bronchopulmonary Dysplasia
Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- Sildenafil in bronchopulmonary dysplasia-associated pulmonary hypertension: developmental and translational insights.Pediatric research · 2026Review
- Pharmacotherapy for Pulmonary Hypertension in Infants with Bronchopulmonary Dysplasia: Past, Present, and Future.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Safety of sildenafil in premature infants at risk of bronchopulmonary dysplasia: Rationale and methods of a phase II randomized trial.Contemporary clinical trials communications · 2022Article
- Pulmonary vasodilator strategies in neonates with acute hypoxemic respiratory failure and pulmonary hypertension.Seminars in fetal & neonatal medicine · 2022Review
- Population pharmacokinetic analysis of sildenafil in term and preterm infants with pulmonary arterial hypertension.Scientific reports · 2022Article
- Wide size dispersion and use of body composition and maturation improves the reliability of allometric exponent estimates.Journal of pharmacokinetics and pharmacodynamics · 2022Article
- The Blind Spot of Pharmacology: A Scoping Review of Drug Metabolism in Prematurely Born Children.Frontiers in pharmacology · 2022Article
- Update on the use of sildenafil in neonatal pulmonary hypertension: a narrative review of the history, current administration, and future directions.Translational pediatrics · 2021Review
- Physiologically-Based Pharmacokinetic Modeling Characterizes the CYP3A-Mediated Drug-Drug Interaction Between Fluconazole and Sildenafil in Infants.Clinical pharmacology and therapeutics · 2021Article
- Therapies that enhance pulmonary vascular NO-signaling in the neonate.Nitric oxide : biology and chemistry · 2020Review
- Prenatal Use of Sildenafil in Fetal Growth Restriction and Its Effect on Neonatal Tissue Oxygenation-A Retrospective Analysis of Hemodynamic Data From Participants of the Dutch STRIDER Trial.Frontiers in pediatrics · 2020Article
- Population pharmacokinetics of sildenafil in extremely premature infants.British journal of clinical pharmacology · 2019Article
Corrections and comments
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Authors and funding
17 authors at 11 institutions in 1 country.
Funding
Abstract
aimsTo characterize the population pharmacokinetics (PK) of sildenafil and its active metabolite, N-desmethyl sildenafil (DMS), in premature infants.
methodsWe performed a multicentre, open-label trial to characterize the 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). In cohort 1, we obtained PK samples from infants receiving sildenafil as ordered per the local standard of care (intravenous [IV] or enteral). In cohort 2, we administered a single IV dose of sildenafil and performed PK sampling. We performed a population PK analysis and dose-exposure simulations using the software NONMEM®.
resultsWe enrolled 34 infants (cohort 1 n = 25; cohort 2 n = 9) and collected 109 plasma PK samples. Sildenafil was given enterally (0.42-2.09 mg/kg) in 24 infants in cohort 1 and via IV (0.125 or 0.25 mg/kg) in all infants in cohort 2. A 2-compartment PK model for sildenafil and 1-compartment model for DMS, with presystemic conversion of sildenafil to DMS, characterized the data well. Coadministration of fluconazole (n = 4), a CYP3A inhibitor, resulted in an estimated 59% decrease in sildenafil clearance. IV doses of 0.125, 0.5 and 1 mg/kg every 8 hours (in the absence of fluconazole) resulted in steady-state maximum sildenafil concentrations that were generally within the range of those reported to inhibit phosphodiesterase type 5 activity in vitro.
conclusionsWe 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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.