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Pharmacokinetics, Pharmacodynamics, Tolerability, and Safety of the Soluble Guanylate Cyclase Activator Cinaciguat (BAY 58‐2667) in Healthy Male Volunteers
Author(s) -
Frey Reiner,
Mück Wolfgang,
Unger Sigrun,
ArtmeierBrandt Ulrike,
Weimann Gerrit,
Wensing Georg
Publication year - 2008
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270008322906
Subject(s) - tolerability , medicine , pharmacokinetics , pharmacodynamics , pharmacology , blood pressure , heart failure , anesthesia , placebo , heart rate , adverse effect , alternative medicine , pathology
Preclinical data indicate that the nitric oxide—independent soluble guanylate cyclase activator cinaciguat (BAY 58–2667), which is a new drug in development for patients with heart failure, induces vasodilation preferentially in diseased vessels. This study aimed to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of cinaciguat. Seventy‐six healthy volunteers were included in this randomized, placebo‐controlled study. Cinaciguat (50–250 μg/h) was administered intravenously for up to 4 hours in a maximum of 6 individuals per dose group. No serious adverse events were reported. Four‐hour infusions (50–250 μg/h) decreased diastolic blood pressure and increased heart rate (all P values < .05) versus placebo, without significantly reducing systolic blood pressure ( P between 0.07 and 0.56). At higher doses (150–250 μg/h), 4‐hour infusions decreased mean arterial pressure and increased plasma cyclic guanosine monophosphate levels (all P values < .05). Pharmacokinetics showed dose‐proportionality with low interindividual variability. Plasma concentrations declined below 1.0 μg/L within 30 minutes of cessation of infusion. Cinaciguat had potent cardiovascular effects reducing preload and afterload, warranting further investigation in patients with heart failure.