An inhaled sGC modulator can lower PH in COPD patients 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 COPD...

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Main Authors: Saffaran, Sina, Wang, Wenfei, Das, Anup, Schmitt, Walter, Becker-Pelster, Eva-Maria, Hardman, Jonathan G., Weimann, Gerrit, Bates, Declan G.
Format: Article
Published: Wiley Open Access 2018
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Online Access:https://eprints.nottingham.ac.uk/51531/
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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
building Nottingham Research Data Repository
collection Online Access
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 COPD patients were configured in the simulator based on clinical data. In agreement with previous clinical studies, modeling systemic application of a soluble guanylate cyclase (sGC) modulator results in reduced partial pressure of oxygen (PaO2) and increased partial pressure of carbon dioxide (PaCO2) 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 while oxygenation is improved with respect to baseline values.
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institution University of Nottingham Malaysia Campus
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spelling nottingham-515312020-05-04T19:44:52Z https://eprints.nottingham.ac.uk/51531/ An inhaled sGC modulator can lower PH in COPD patients without deteriorating oxygenation Saffaran, Sina Wang, Wenfei Das, Anup Schmitt, Walter Becker-Pelster, Eva-Maria Hardman, Jonathan G. Weimann, Gerrit Bates, Declan G. 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 COPD patients were configured in the simulator based on clinical data. In agreement with previous clinical studies, modeling systemic application of a soluble guanylate cyclase (sGC) modulator results in reduced partial pressure of oxygen (PaO2) and increased partial pressure of carbon dioxide (PaCO2) 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 while oxygenation is improved with respect to baseline values. Wiley Open Access 2018-07-02 Article PeerReviewed Saffaran, Sina, Wang, Wenfei, Das, Anup, Schmitt, Walter, Becker-Pelster, Eva-Maria, Hardman, Jonathan G., Weimann, Gerrit and Bates, Declan G. (2018) An inhaled sGC modulator can lower PH in COPD patients without deteriorating oxygenation. CPT: Pharmacometrics & Systems Pharmacology . ISSN 2163-8306 pulmonary hypertension chronic obstructive pulmonary disease soluble guanylate cyclase modulators computer simulation https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1002/psp4.12308 doi:10.1002/psp4.12308 doi:10.1002/psp4.12308
spellingShingle pulmonary hypertension
chronic obstructive pulmonary disease
soluble guanylate cyclase modulators
computer simulation
Saffaran, Sina
Wang, Wenfei
Das, Anup
Schmitt, Walter
Becker-Pelster, Eva-Maria
Hardman, Jonathan G.
Weimann, Gerrit
Bates, Declan G.
An inhaled sGC modulator can lower PH in COPD patients without deteriorating oxygenation
title An inhaled sGC modulator can lower PH in COPD patients without deteriorating oxygenation
title_full An inhaled sGC modulator can lower PH in COPD patients without deteriorating oxygenation
title_fullStr An inhaled sGC modulator can lower PH in COPD patients without deteriorating oxygenation
title_full_unstemmed An inhaled sGC modulator can lower PH in COPD patients without deteriorating oxygenation
title_short An inhaled sGC modulator can lower PH in COPD patients without deteriorating oxygenation
title_sort inhaled sgc modulator can lower ph in copd patients without deteriorating oxygenation
topic pulmonary hypertension
chronic obstructive pulmonary disease
soluble guanylate cyclase modulators
computer simulation
url https://eprints.nottingham.ac.uk/51531/
https://eprints.nottingham.ac.uk/51531/
https://eprints.nottingham.ac.uk/51531/