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

@article{Frey2008PharmacokineticsPT,
  title={Pharmacokinetics, Pharmacodynamics, Tolerability, and Safety of the Soluble Guanylate Cyclase Activator Cinaciguat (BAY 58‐2667) in Healthy Male Volunteers},
  author={Reiner Frey and Wolfgang M{\"u}ck and Sigrun Unger and Ulrike Artmeier-Brandt and Gerrit Weimann and Georg Wensing},
  journal={The Journal of Clinical Pharmacology},
  year={2008},
  volume={48}
}
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… 

Population Pharmacokinetics and Pharmacodynamics of Cinaciguat, a Soluble Guanylate Cyclase Activator, in Patients with Acute Decompensated Heart Failure

Intravenously administered cinaciguat had predictable pharmacokinetic and haemodynamic effects in patients with ADHF.

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Cinaciguat, a soluble guanylate cyclase activator, unloads the heart but also causes hypotension in acute decompensated heart failure.

Cinaciguat unloaded the heart in patients with ADHF, however, high doses were associated with hypotension and the trial was stopped prematurely due to an increased occurrence of hypotension at cinacigsuat doses ≥200 µg/h.

Assessment of the Effects of Renal Impairment on the Pharmacokinetics of the Soluble Guanylate Cyclase Activator Cinaciguat After a Single Intravenous Dose

Cinaciguat, a promising drug candidate for the treatment of acute decompensated heart failure, will not require dose adjustment based on renal function, and its pharmacokinetic variability tended to be somewhat increased in individuals with renal impairment.

Pharmacokinetics of the Soluble Guanylate Cyclase Activator Cinaciguat in Individuals With Hepatic Impairment

It is demonstrated that in individuals with mild hepatic impairment, individual dose adaptation may not be required and cinaciguat was well tolerated and had a favorable safety profile.

Cinaciguat (BAY 58–2667) Improves Cardiopulmonary Hemodynamics in Patients With Acute Decompensated Heart Failure

Cinaciguat has potent preload- and afterload-reducing effects, increasing cardiac output and well tolerated, with 13 of 60 patients reporting 14 drug-related treatment-emergent adverse events of mild to moderate intensity.

A novel soluble guanylate cyclase activator with reduced risk of hypotension by short‐acting vasodilation

TY‐55002 is a novel short‐acting sGC activator, which offers the possibility of easy dose management without excessive hypotension and holds potential to serve as an innovative drug in the pharmacotherapy of ADHF.

Cinaciguat (BAY-582667) Modifies Cardiopulmonary and Systemic Circulation in Chronically Hypoxic and Pulmonary Hypertensive Neonatal Lambs in the Alto Andino

Cinaciguat, an activator of sGC, induces cardiopulmonary modifications in chronically hypoxic and pulmonary hypertensive newborn lambs and is a potential therapeutic tool for reducing pulmonary vascular remodeling and/or right ventricular hypertrophy in pulmonary arterial hypertension syndrome.

Role of guanylate cyclase modulators in decompensated heart failure

Preliminary studies of cinaciguat in patients with acute decompensated heart failure show substantial improvements in haemodynamics and symptoms, whilst maintaining renal function.
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