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.

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.

Citation

Saffaran, S., Wang, W., Das, A., Schmitt, W., Becker-Pelster, E., Hardman, J. G., …Bates, D. G. (2018). An inhaled sGC modulator can lower PH in COPD patients without deteriorating oxygenation. CPT: Pharmacometrics and Systems Pharmacology, 7(8), 491-498. https://doi.org/10.1002/psp4.12308

• Journal Article Type: Article
• Acceptance Date: Apr 26, 2018
• Online Publication Date: Jul 2, 2018
• Publication Date: 2018-08
• Deposit Date: May 2, 2018
• Publicly Available Date: Jul 2, 2018
• Journal: CPT: Pharmacometrics & Systems Pharmacology
• Electronic ISSN: 2163-8306
• Publisher: Wiley Open Access
• Peer Reviewed: Peer Reviewed
• Volume: 7
• Issue: 8
• Pages: 491-498
• DOI: https://doi.org/10.1002/psp4.12308
• Keywords: pulmonary hypertension, chronic obstructive pulmonarydisease, soluble guanylate cyclase modulators, computer simulation
• Public URL: https://nottingham-repository.worktribe.com/output/944862
• Publisher URL: https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1002/psp4.12308