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...
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Nature Portfolio
2022-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-11038-6 |
| _version_ | 1817985396476215296 |
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| author | Su-jin Rhee Seung Han Shin Jaeseong Oh Young Hwa Jung Chang Won Choi Han-Suk Kim Kyung-Sang Yu |
| author_facet | Su-jin Rhee Seung Han Shin Jaeseong Oh Young Hwa Jung Chang Won Choi Han-Suk Kim Kyung-Sang Yu |
| author_sort | Su-jin Rhee |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T23:56:45Z |
| format | Article |
| id | doaj.art-8229bf95561f4c5abd697f714839cfda |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T23:56:45Z |
| publishDate | 2022-05-01 |
| publisher | Nature Portfolio |
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| spelling | doaj.art-8229bf95561f4c5abd697f714839cfda2022-12-22T02:23:51ZengNature PortfolioScientific Reports2045-23222022-05-0112111110.1038/s41598-022-11038-6Population pharmacokinetic analysis of sildenafil in term and preterm infants with pulmonary arterial hypertensionSu-jin Rhee0Seung Han Shin1Jaeseong Oh2Young Hwa Jung3Chang Won Choi4Han-Suk Kim5Kyung-Sang Yu6Department of Pharmacy, Wonkwang University College of PharmacyDepartment of Pediatrics, Seoul National University Hospital, Seoul National University College of MedicineDepartment of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and HospitalDepartment of Pediatrics, Seoul National University Bundang Hospital, Seoul National University College of MedicineDepartment of Pediatrics, Seoul National University Bundang Hospital, Seoul National University College of MedicineDepartment of Pediatrics, Seoul National University Hospital, Seoul National University College of MedicineDepartment of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and HospitalAbstract 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.https://doi.org/10.1038/s41598-022-11038-6 |
| spellingShingle | Su-jin Rhee Seung Han Shin Jaeseong Oh Young Hwa Jung Chang Won Choi Han-Suk Kim Kyung-Sang Yu Population pharmacokinetic analysis of sildenafil in term and preterm infants with pulmonary arterial hypertension Scientific Reports |
| title | Population pharmacokinetic analysis of sildenafil in term and preterm infants with pulmonary arterial hypertension |
| title_full | Population pharmacokinetic analysis of sildenafil in term and preterm infants with pulmonary arterial hypertension |
| title_fullStr | Population pharmacokinetic analysis of sildenafil in term and preterm infants with pulmonary arterial hypertension |
| title_full_unstemmed | Population pharmacokinetic analysis of sildenafil in term and preterm infants with pulmonary arterial hypertension |
| title_short | Population pharmacokinetic analysis of sildenafil in term and preterm infants with pulmonary arterial hypertension |
| title_sort | population pharmacokinetic analysis of sildenafil in term and preterm infants with pulmonary arterial hypertension |
| url | https://doi.org/10.1038/s41598-022-11038-6 |
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