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Inhaled sGC modulator can lower PH in patients with COPD without deteriorating oxygenation
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Saffaran, Sina, Wang, Wenfei, Das, Anup, Schmitt, Walter, Becker-Pelster, Eva-Maria, Hardman, Jonathan G., Weimann, Gerrit and Bates, Declan (2018) Inhaled sGC modulator can lower PH in patients with COPD without deteriorating oxygenation. CPT: pharmacometrics & systems pharmacology . doi:10.1002/psp4.12308 (In Press)
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Official URL: https://doi.org/10.1002/psp4.12308
Abstract
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.
| Item Type: | Journal Article | ||||||||
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| Divisions: | Faculty of Science > Engineering | ||||||||
| Journal or Publication Title: | CPT: pharmacometrics & systems pharmacology | ||||||||
| Publisher: | Wiley-Blackwell Publishing Ltd. | ||||||||
| ISSN: | 2163-8306 | ||||||||
| Official Date: | 2 July 2018 | ||||||||
| Dates: |
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| Date of first compliant deposit: | 30 August 2018 | ||||||||
| DOI: | 10.1002/psp4.12308 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | In Press | ||||||||
| Access rights to Published version: | Open Access | ||||||||
| Copyright Holders: | ASCPT | ||||||||
| Funder: | Bayer Healthcare, Engineering and Physical Sciences Research Council (EPSRC) | ||||||||
| Grant number: | EP/P023444/1 | ||||||||
| Open Access Version: |
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