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BAY 63–2521, an oral soluble guanylate cyclase stimulator, has a favourable safety profile and decreases peripheral vascular resistance in healthy male volunteers
© Frey 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. Preclinical data suggest that BAY 63–2521 has the potential to be effective in the treatment of pulmonary hypertension, with the advantage of having a different mode of action from currently available agents.
Materials and methods
This randomized, placebo-controlled, single-blinded study assessed the safety, tolerability, pharmacodynamics and pharmacokinetics of orally administered BAY 63–2521 in healthy male volunteers. Subjects received a single oral dose of BAY 63–2521 in solution (0.25 mg, n = 6; 0.5 mg n = 5; 1 mg, n = 12; 2.5 mg, n = 6; 5 mg, n = 10) or as an immediate-release tablet (2.5 mg, n = 6), or matching placebo solution (n = 11) or a placebo tablet (n = 2). Safety parameters (adverse events [AEs], electrocardiograms [ECGs] and standard laboratory values), pharmacodynamics (heart rate [HR], systolic blood pressure [SBP], diastolic blood pressure [DBP], cyclic guanosine monophosphate [cGMP] levels and plasma vasoactive hormone levels) and pharmacokinetics were assessed.
Increase in heart rate after oral administration of BAY 63–2521 in solution, compared with placebo.
Increase in heart rate (beats/minute)
95% confidence interval
(-5.10 to 2.40)
(-3.45 to 4.32)
(1.10 to 7.08)
(4.22 to 11.32)
(8.29 to 14.39)
BAY 63–2521 had a favourable safety profile and was well-tolerated up to a single oral dose of 5 mg. In line with its mode of action as an sGC stimulator, BAY 63–2521 dose-dependently reduced DBP and increased HR. Further studies are warranted to assess the therapeutic potential of BAY 63–2521 in patients with pulmonary hypertension.
This article is published under license to BioMed Central Ltd.