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Inhaled sGC Modulator Can Lower PH in Patients With COPD Without Deteriorating Oxygenation

This study uses a highly fidelity computational simulator of pulmonary physiology to evaluate the impact of a soluble guanylate cyclase (sGC) modulator on gas exchange in patients with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH) as a complication. Three virtual patie...

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Detalles Bibliográficos
Autores principales: Saffaran, Sina, Wang, Wenfei, Das, Anup, Schmitt, Walter, Becker‐Pelster, Eva‐Maria, Hardman, Jonathan G., Weimann, Gerrit, Bates, Declan G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6118299/
https://www.ncbi.nlm.nih.gov/pubmed/29962065
http://dx.doi.org/10.1002/psp4.12308
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author Saffaran, Sina
Wang, Wenfei
Das, Anup
Schmitt, Walter
Becker‐Pelster, Eva‐Maria
Hardman, Jonathan G.
Weimann, Gerrit
Bates, Declan G.
author_facet Saffaran, Sina
Wang, Wenfei
Das, Anup
Schmitt, Walter
Becker‐Pelster, Eva‐Maria
Hardman, Jonathan G.
Weimann, Gerrit
Bates, Declan G.
author_sort Saffaran, Sina
collection PubMed
description This study uses a highly fidelity computational simulator of pulmonary physiology to evaluate the impact of a soluble guanylate cyclase (sGC) modulator on gas exchange in patients with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH) as a complication. Three virtual patients with COPD were configured in the simulator based on clinical data. In agreement with previous clinical studies, modeling systemic application of an sGC modulator results in reduced partial pressure of oxygen (PaO(2)) and increased partial pressure of carbon dioxide (PaCO(2)) in arterial blood, if a drug‐induced reduction of pulmonary vascular resistance (PVR) equal to that observed experimentally is assumed. In contrast, for administration via dry powder inhalation (DPI), our simulations suggest that the treatment results in no deterioration in oxygenation. For patients under exercise, DPI administration lowers PH, whereas oxygenation is improved with respect to baseline values.
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spelling pubmed-61182992018-09-04 Inhaled sGC Modulator Can Lower PH in Patients With COPD Without Deteriorating Oxygenation Saffaran, Sina Wang, Wenfei Das, Anup Schmitt, Walter Becker‐Pelster, Eva‐Maria Hardman, Jonathan G. Weimann, Gerrit Bates, Declan G. CPT Pharmacometrics Syst Pharmacol Research This study uses a highly fidelity computational simulator of pulmonary physiology to evaluate the impact of a soluble guanylate cyclase (sGC) modulator on gas exchange in patients with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH) as a complication. Three virtual patients with COPD were configured in the simulator based on clinical data. In agreement with previous clinical studies, modeling systemic application of an sGC modulator results in reduced partial pressure of oxygen (PaO(2)) and increased partial pressure of carbon dioxide (PaCO(2)) in arterial blood, if a drug‐induced reduction of pulmonary vascular resistance (PVR) equal to that observed experimentally is assumed. In contrast, for administration via dry powder inhalation (DPI), our simulations suggest that the treatment results in no deterioration in oxygenation. For patients under exercise, DPI administration lowers PH, whereas oxygenation is improved with respect to baseline values. John Wiley and Sons Inc. 2018-07-02 2018-08 /pmc/articles/PMC6118299/ /pubmed/29962065 http://dx.doi.org/10.1002/psp4.12308 Text en © 2018 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Saffaran, Sina
Wang, Wenfei
Das, Anup
Schmitt, Walter
Becker‐Pelster, Eva‐Maria
Hardman, Jonathan G.
Weimann, Gerrit
Bates, Declan G.
Inhaled sGC Modulator Can Lower PH in Patients With COPD Without Deteriorating Oxygenation
title Inhaled sGC Modulator Can Lower PH in Patients With COPD Without Deteriorating Oxygenation
title_full Inhaled sGC Modulator Can Lower PH in Patients With COPD Without Deteriorating Oxygenation
title_fullStr Inhaled sGC Modulator Can Lower PH in Patients With COPD Without Deteriorating Oxygenation
title_full_unstemmed Inhaled sGC Modulator Can Lower PH in Patients With COPD Without Deteriorating Oxygenation
title_short Inhaled sGC Modulator Can Lower PH in Patients With COPD Without Deteriorating Oxygenation
title_sort inhaled sgc modulator can lower ph in patients with copd without deteriorating oxygenation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6118299/
https://www.ncbi.nlm.nih.gov/pubmed/29962065
http://dx.doi.org/10.1002/psp4.12308
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