BAY 63–2521, an oral soluble guanylate cyclase stimulator, has a favourable safety profile, improves cardiopulmonary haemodynamics and has therapeutic potential in pulmonary hypertension
© Ghofrani et al; licensee BioMed Central Ltd. 2007
Published: 25 July 2007
BAY 63–2521 is an oral soluble guanylate cyclase (sGC) stimulator that acts independently of nitric oxide (NO). It targets the reduced form of sGC, and enhances the sensitivity of the enzyme to low levels of bioavailable NO. Phase I clinical trial results suggest that BAY 63–2521 has a favourable safety profile in healthy volunteers. This proof-of-concept study evaluated BAY 63–2521 in patients with moderate-to-severe pulmonary hypertension (pulmonary vascular resistance [PVR] > 300 dyn·s·cm-5).
Materials and methods
This two-part non-randomized, non-blinded, single-site study assessed safety, tolerability, cardiopulmonary haemodynamics, gas exchange and ventilation-perfusion mismatch (VQM). Tolerability of 2.5 mg and 5 mg total doses of BAY 63–2521 was evaluated in 2 × 2 patients given hourly incremental doses (0.5 + 1 + 1 mg = 2.5 mg; 1 + 2 + 2 mg = 5 mg). Further evaluation of 1 mg and 2.5 mg doses was performed in 15 patients and included Swan-Ganz haemodynamics, multiple inert gas elimination technique (MIGET) and blood gas analysis. Results were compared with peak intervention values for inhaled NO (iNO) (8–20 ppm) and one-time post-NO-intervention baseline values. Adverse events (AEs), vital signs, electrocardiograms (ECGs) and laboratory values were monitored.
Haemodynamic effects of BAY 63–2521, 2.5 mg
Cardiac index (L/min/m2)
BAY 63–2521 has a favourable safety profile and does not alter gas exchange or VQM at single doses up to 2.5 mg in patients with moderate-to-severe pulmonary hypertension. This agent improved all main haemodynamic parameters in a dose-dependent manner and to a greater extent than iNO. BAY 63–2521 has therapeutic potential and further studies are warranted.
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