Based on a population pharmacokinetics model, sildenafil doses higher than 1 mg/kg are necessary to achieve and maintain target concentrations of the drug and reach timely clinical effects in term and preterm infants with pulmonary arterial hypertension (PAH). This is according to a new study published in Scientific Reports

“These results could be utilized for the safer and more effective use of sildenafil in term and preterm infants,” according to the authors of the study.

Off-label sildenafil is used widely to treat children with PAH. Here, a team of researchers led by Kyung-Sang Yu, MD, from the Department of Clinical Pharmacology and Therapeutics at Seoul National University College of Medicine and Hospital in the Republic of Korea developed a population model to characterize the pharmacokinetics of sildenafil in term and preterm infants with PAH. The model could be used to indicate appropriate treatment doses to achieve concentrations that are clinically effective.

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The team analyzed the concentrations of sildenafil and N-desmethyl sildenafil (DMS), the metabolite of sildenafil, in 19 newborn babies with PAH. The babies received 0.5 to 0.75 mg/kg of sildenafil 4 times a day. 

The researchers conducted simulations according to the babies’ body weights, a covariate for the clearance of sildenafil, and they were able to adequately describe the pharmacokinetics of sildenafil and DMS.

“This study established a population [pharmacokinetics] model that adequately describes the [pharmacokinetics] of sildenafil in term and preterm infants with PAH, and presented the rationale for setting an appropriate body weight based dose,” the researchers concluded.

Sildenafil is a selective phosphodiesterase type 5 inhibitor. It is approved in the United States and Europe for the treatment of adult patients with PAH. The US Food and Drug Administration (FDA) recommends against the use of sildenafil in children, while the European Medicines Agency (EMA) allows the use of the drug in patients with PAH as young as 1 year of age. The treatment is used off-label in newborns, usually at a dose of 0.5 to 2 mg/kg.


Rhee SJ, Shin SH, Oh J, et al. Population pharmacokinetic analysis of sildenafil in term and preterm infants with pulmonary arterial hypertension. Sci Rep. 2022;12(1):7393. doi:10.1038/s41598-022-11038-6