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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Publikationen des W. G. Kerckhoff-Instituts     Display Documents



ID: 428394.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Publikationen des W. G. Kerckhoff-Instituts
First acute haemodynamic study of soluble guanylate cyclase stimulator riociguat in pulmonary hypertension
Authors:Grimminger, F.; Weimann, G.; Frey, R.; Voswinckel, R.; Thamm, M.; Bolkow, D.; Weissmann, N.; Muck, W.; Unger, S.; Wensing, G.; Schermuly, R. T.; Ghofrani, H. A.
Date of Publication (YYYY-MM-DD):2009
Title of Journal:Eur Respir J
Audience:Not Specified
Abstract / Description:Pulmonary hypertension (PH) is associated with impaired production of the vasodilator nitric oxide (NO). Riociguat (BAY 63-2521) acts directly on soluble guanylate cyclase, stimulating the enzyme and increasing sensitivity to low NO levels. This 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 ten and five patients with PH respectively. All subjects were analysed for safety and tolerability (n=19).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.This is the first report describing the use of riociguat in patients with PH. The drug was well-tolerated and superior to NO in efficacy and duration. Riociguat therefore has potential as a novel therapy for PH, and warrants further investigation.
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für physiologische und klinische Forschung
Identifiers:URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=...
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