Update on the use of sildenafil in neonatal pulmonary hypertension: a narrative review of the history, current administration, and future directions

Abstract

Pulmonary hypertension (PH) is a life-threatening syndrome in neonates and has multiple and varied etiologies. However, few clinical studies have systematically evaluated the treatment regimens for this population. Phosphodiesterase (PDE) inhibitors, such as milrinone, tadalafil, dipyridamole, and sildenafil, are the most important regulators of vascular relaxation in the normal pulmonary vascular transition after birth, and these agents are widely used in the treatment of PH. Sildenafil, a representative PDE-5 inhibitor, has an important role as a single mode of therapy. However, the lack of evidence from pharmacokinetic and clinical trials has limited the emergence of standardized treatment regimens for sildenafil. There are also differing opinions among researchers regarding the best route of sildenafil administration. Due to the interindividual variability in the neonatal population, it is worth selecting the most suitable route of sildenafil administration according to the specific conditions of the neonatal population. These may be evaluated using the oxygenation index (OI), pulmonary artery pressure, mean blood pressure, and the serological index. This article reviews the clinical data on the use of sildenafil, focusing on the current and promising alternative routes of administration, which may affect subsequent clinical research in term and preterm neonates.

Electrospinning of pullulan-based orodispersible films containing sildenafil

“…Based on these premises, the aim of the present work was to preliminarily evaluate the feasibility of electrospinning in the manufacturing of pullulan-based ODFs intended for the administration of sildenafil to pediatric patients. Indeed, sildenafil was recently proven useful in the treatment of persistent pulmonary hypertension in newborns and children, improving oxygenation index and pulmonary arterial pressure [Dhariwal et al, 2015;Evers et al, 2021;He et al, 2021b;Li et al, 2021;Zhang et al, 2020]. In this respect, oral administration of 0.1 to 0.5 mg/kg every 8 h was recommended, eventually customizing the dosing regimen based on therapy response [Abman et al, 2015].…”