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, 7 (8). pp. 491-498. doi:10.1002/psp4.12308 ISSN 2163-8306.

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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
Divisions:	Faculty of Science, Engineering and Medicine > Engineering > Engineering
Journal or Publication Title:	CPT: pharmacometrics & systems pharmacology
Publisher:	Wiley-Blackwell Publishing Ltd.
ISSN:	2163-8306
Official Date:	August 2018
Dates:	Date Event August 2018 Published 2 July 2018 Available 25 April 2018 Accepted 14 March 2018 Submitted
Volume:	7
Number:	8
Page Range:	pp. 491-498
DOI:	10.1002/psp4.12308
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Copyright Holders:	ASCPT
Date of first compliant deposit:	30 August 2018
Date of first compliant Open Access:	31 August 2018
Funder:	Bayer Healthcare, Engineering and Physical Sciences Research Council (EPSRC)
Grant number:	EP/P023444/1
Open Access Version:	Publisher

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