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Pharmacokinetics of treprostinil in children with functional single-ventricle pulmonary arterial hypertension: a randomized controlled trial

BACKGROUND: Application of Treprostinil (TRE) in the patients with single ventricle (SV) physiology is very limited, and the optimal dose for children has not been determined. In this study, we aimed to analyze plasma samples to assess the attainment of clinically therapeutic concentrations of TRE a...

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Autores principales: Chen, Xi, Cai, Xiao-Man, Zhang, Ming-Jie, Xu, Jing-Han, Li, Hao, Xu, Zhuo-Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350654/
https://www.ncbi.nlm.nih.gov/pubmed/34430604
http://dx.doi.org/10.21037/atm-21-3188
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author Chen, Xi
Cai, Xiao-Man
Zhang, Ming-Jie
Xu, Jing-Han
Li, Hao
Xu, Zhuo-Ming
author_facet Chen, Xi
Cai, Xiao-Man
Zhang, Ming-Jie
Xu, Jing-Han
Li, Hao
Xu, Zhuo-Ming
author_sort Chen, Xi
collection PubMed
description BACKGROUND: Application of Treprostinil (TRE) in the patients with single ventricle (SV) physiology is very limited, and the optimal dose for children has not been determined. In this study, we aimed to analyze plasma samples to assess the attainment of clinically therapeutic concentrations of TRE and its efficacy and safety in the treatment of pediatric functional SV pulmonary arterial hypertension (FSV-PAH).. METHODS: Pediatric patients with FSV-PAH were recruited in this study. IV TRE at an initial rate of 5 ng/kg/min was administered through the femoral vein with an increase in rate to 10 ng/kg/min every 30 minuntil the aiming dose of 80 ng/kg/min had been reached. The drug was gradually discontinued after 12 h of treatment at a stable dose. The mean postoperative pulmonary artery pressure (mPAP), pulmonary-to-systemic arterial pressure ratio (Pp/Ps), and the ratio between arterial oxygen partial pressure and inhaled oxygen concentration (PaO(2)/FiO(2)) were used to evaluate the efficacy of TRE treatment. A multiple linear regression model was used to explore the relevant factors associated with TRE blood concentration. RESULTS: A total of eight patients were enrolled in the investigation, with an age range of 2.5–9.9 years. The median stable dose of TRE was 70 ng/kg/min with a range of 55–75 ng/kg/min. The median subliminal dose was 55 ng/kg/min with a range of 25–75 ng/kg/min. A linear relationship was established between the TRE dose and the plasma concentration. TRE blood concentrations were associated with dose and patient height. After TRE treatment, mPAP, Pp/Ps, and PaO(2)/FiO(2) were significantly improved (P<0.05). CONCLUSIONS: A linear relationship was found between the blood concentration of TRE and its dose. IV TRE was an effective therapy without serious side effects in pediatric patients with FSV-PAH. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02865733.
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spelling pubmed-83506542021-08-23 Pharmacokinetics of treprostinil in children with functional single-ventricle pulmonary arterial hypertension: a randomized controlled trial Chen, Xi Cai, Xiao-Man Zhang, Ming-Jie Xu, Jing-Han Li, Hao Xu, Zhuo-Ming Ann Transl Med Original Article BACKGROUND: Application of Treprostinil (TRE) in the patients with single ventricle (SV) physiology is very limited, and the optimal dose for children has not been determined. In this study, we aimed to analyze plasma samples to assess the attainment of clinically therapeutic concentrations of TRE and its efficacy and safety in the treatment of pediatric functional SV pulmonary arterial hypertension (FSV-PAH).. METHODS: Pediatric patients with FSV-PAH were recruited in this study. IV TRE at an initial rate of 5 ng/kg/min was administered through the femoral vein with an increase in rate to 10 ng/kg/min every 30 minuntil the aiming dose of 80 ng/kg/min had been reached. The drug was gradually discontinued after 12 h of treatment at a stable dose. The mean postoperative pulmonary artery pressure (mPAP), pulmonary-to-systemic arterial pressure ratio (Pp/Ps), and the ratio between arterial oxygen partial pressure and inhaled oxygen concentration (PaO(2)/FiO(2)) were used to evaluate the efficacy of TRE treatment. A multiple linear regression model was used to explore the relevant factors associated with TRE blood concentration. RESULTS: A total of eight patients were enrolled in the investigation, with an age range of 2.5–9.9 years. The median stable dose of TRE was 70 ng/kg/min with a range of 55–75 ng/kg/min. The median subliminal dose was 55 ng/kg/min with a range of 25–75 ng/kg/min. A linear relationship was established between the TRE dose and the plasma concentration. TRE blood concentrations were associated with dose and patient height. After TRE treatment, mPAP, Pp/Ps, and PaO(2)/FiO(2) were significantly improved (P<0.05). CONCLUSIONS: A linear relationship was found between the blood concentration of TRE and its dose. IV TRE was an effective therapy without serious side effects in pediatric patients with FSV-PAH. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02865733. AME Publishing Company 2021-07 /pmc/articles/PMC8350654/ /pubmed/34430604 http://dx.doi.org/10.21037/atm-21-3188 Text en 2021 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Chen, Xi
Cai, Xiao-Man
Zhang, Ming-Jie
Xu, Jing-Han
Li, Hao
Xu, Zhuo-Ming
Pharmacokinetics of treprostinil in children with functional single-ventricle pulmonary arterial hypertension: a randomized controlled trial
title Pharmacokinetics of treprostinil in children with functional single-ventricle pulmonary arterial hypertension: a randomized controlled trial
title_full Pharmacokinetics of treprostinil in children with functional single-ventricle pulmonary arterial hypertension: a randomized controlled trial
title_fullStr Pharmacokinetics of treprostinil in children with functional single-ventricle pulmonary arterial hypertension: a randomized controlled trial
title_full_unstemmed Pharmacokinetics of treprostinil in children with functional single-ventricle pulmonary arterial hypertension: a randomized controlled trial
title_short Pharmacokinetics of treprostinil in children with functional single-ventricle pulmonary arterial hypertension: a randomized controlled trial
title_sort pharmacokinetics of treprostinil in children with functional single-ventricle pulmonary arterial hypertension: a randomized controlled trial
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350654/
https://www.ncbi.nlm.nih.gov/pubmed/34430604
http://dx.doi.org/10.21037/atm-21-3188
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