J Clin Pharmacol
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First published on September 8, 2008, doi:10.1177/0091270008322906

The Journal of Clinical Pharmacology 2008;48:1400.

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©© 2008 American College of Clinical Pharmacology, Inc.
The Journal of Clinical Pharmacology, 10.1177/0091270008322906

Article

Pharmacokinetics, Pharmacodynamics, Tolerability and Safety of the Soluble Guanylate Cyclase Activator Cinaciguat (BAY 58-2667) in Healthy Male Volunteers

Reiner Frey 1*, Wolfgang Mück 1, Sigrun Unger 1, Ulrike Artmeier-Brandt 1, Gerrit Weimann 1, and Georg Wensing 1

1 Bayer HealthCare AG

* To whom correspondence should be addressed. E-mail: reiner.frey{at}bayerhealthcare.com.


  Abstract
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.
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