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


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.

SUBMITTER: Rhee SJ 

PROVIDER: S-EPMC9072418 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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

Rhee Su-Jin SJ   Shin Seung Han SH   Oh Jaeseong J   Jung Young Hwa YH   Choi Chang Won CW   Kim Han-Suk HS   Yu Kyung-Sang KS  

Scientific reports 20220505 1


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,  ...[more]

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