RT Journal Article
SR Electronic
T1 First acute haemodynamic study of soluble guanylate cyclase stimulator riociguat in pulmonary hypertension
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 785
OP 792
DO 10.1183/09031936.00039808
VO 33
IS 4
A1 F. Grimminger
A1 G. Weimann
A1 R. Frey
A1 R. Voswinckel
A1 M. Thamm
A1 D. Bölkow
A1 N. Weissmann
A1 W. Mück
A1 S. Unger
A1 G. Wensing
A1 R. T. Schermuly
A1 H.A. Ghofrani
YR 2009
UL http://erj.ersjournals.com/content/33/4/785.abstract
AB Pulmonary hypertension (PH) is associated with impaired production of the vasodilator nitric oxide (NO). Riociguat (BAY 63-2521; Bayer Healthcare AG, Wuppertal, Germany) acts directly on soluble guanylate cyclase, stimulating the enzyme and increasing sensitivity to low NO levels. The present study evaluates riociguat safety, tolerability and efficacy in patients with moderate-to-severe PH (pulmonary arterial hypertension, distal chronic thromboembolic PH or PH with mild to moderate interstitial lung disease). The optimal tolerated dose was identified by incremental dosing in four patients with PH; pharmacodynamic and pharmacokinetic parameters were assessed following single-dose administration (2.5 mg or 1 mg) in 10 and five patients with PH, respectively. All subjects (n = 19) were analysed for safety and tolerability. Riociguat had a favourable safety profile at single doses ≤2.5 mg. It significantly improved pulmonary haemodynamic parameters and cardiac index in patients with PH in a dose-dependent manner, to a greater extent than inhaled NO. Although riociguat also had significant systemic effects and showed no pulmonary selectivity, mean systolic blood pressure remained >110 mmHg. The present report is the first to describe the use of riociguat in patients with pulmonary hypertension. The drug was well-tolerated and superior to nitric oxide in efficacy and duration. Riociguat, therefore, has potential as a novel therapy for pulmonary hypertension and warrants further investigation.