{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T16:53:20Z","timestamp":1772988800529,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Co\u2010administration of oral phosphodiesterase 5 inhibitors with oral soluble guanylate cyclase (sGC) stimulators is contraindicated due to the risk of systemic side effects. Frespaciguat, an inhaled sGC stimulator, has been studied in pulmonary hypertension (PH)\u2010related conditions such as pulmonary arterial hypertension (PAH) and PH associated with chronic obstructive pulmonary disease (PH\u2010COPD), and may allow combined use with oral PDE5i due to low systemic exposure. To evaluate a potential interaction between inhaled frespaciguat and oral sildenafil, 19 healthy participants were randomized to two treatment sequences (two periods separated by a 36\u2010h washout). Treatment involved 3 days of dosing with open\u2010label oral sildenafil (20\u00a0mg, three times per day) and a single inhaled dose of frespaciguat 240\u00a0\u00b5g or placebo on Day 3. Primary endpoints included safety assessed by adverse events (AEs) and change from baseline in systolic and diastolic blood pressure, and heart rate. Incidence of AEs was comparable across groups with no serious AEs, discontinuations due to AEs, or deaths. In conclusion, inhaled frespaciguat was well tolerated when administered on background sildenafil, without negative effects on systemic hemodynamics, versus placebo. The lack of additive systemic effects on blood pressure further documents pulmonary selectivity of inhaled frespaciguat, including when co\u2010administered with sildenafil (EudraCT number 2019\u2010001224\u201035).<\/jats:p>","DOI":"10.1002\/cpdd.70035","type":"journal-article","created":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T04:34:51Z","timestamp":1771043691000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phase 1 Study Evaluating the Effects of Single\u2010Dose Frespaciguat, an Inhaled Soluble Guanylate Cyclase Stimulator, Co\u2010administered with Multiple\u2010Dose Sildenafil on Systemic Hemodynamics"],"prefix":"10.1002","volume":"15","author":[{"given":"Ednan K.","family":"Bajwa","sequence":"first","affiliation":[{"name":"MRL Merck &amp; Co., Inc.  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