Population pharmacokinetic analysis of sildenafil in term and preterm infants with pulmonary arterial hypertension

Autor: Su-jin Rhee, Seung Han Shin, Jaeseong Oh, Young Hwa Jung, Chang Won Choi, Han-Suk Kim, Kyung-Sang Yu
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Scientific Reports, Vol 12, Iss 1, Pp 1-11 (2022)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-022-11038-6
Popis: Abstract Sildenafil is widely used off-label in pediatric patients with pulmonary arterial hypertension (PAH). This study was conducted to characterize the pharmacokinetics (PK) of sildenafil in term and preterm neonates with PAH, by developing a population PK model, and to suggest appropriate doses to achieve clinically effective concentrations. A population PK modelling analysis was performed using sildenafil and its metabolite N-desmethyl sildenafil (DMS) concentration data from 19 neonates with PAH, whose gestational ages ranged 24–41 weeks. They received sildenafil orally at a dose of 0.5–0.75 mg/kg, four times a day. To investigate the appropriate sildenafil dose, simulations were conducted according to body weight which was significant covariate for sildenafil clearance. A one-compartment model with first-order absorption adequately described the PKs of sildenafil and DMS. Sildenafil clearance was expected to increase rapidly with increasing body weight. In the simulation, sildenafil doses > 1 mg/kg was required to achieve and maintain target concentrations of sildenafil and to expect timely clinical effects in term and preterm infants. These results could be utilized for the safer and more effective use of sildenafil in term and preterm infants.
Databáze: Directory of Open Access Journals
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