Riociguat for pulmonary hypertension.
Pulmonary hypertension (PH) encompasses a group of diseases associated with progressively increasing pulmonary vascular resistance, right heart failure and premature death. Riociguat is a novel, first-in-class oral drug that directly stimulates soluble guanylate cyclase, both independently of the endogenous vasodilator nitric oxide (NO) and in synergy with NO. Single oral doses of riociguat were well tolerated in a Phase I study of healthy volunteers. They had a favorable safety profile, and improved pulmonary hemodynamics and cardiac index to a greater extent than inhaled NO in a proof-of-concept study in patients with moderate-to-severe PH. In a 12-week Phase II trial in patients with chronic thromboembolic PH or pulmonary arterial hypertension, pulmonary hemodynamics and exercise capacity improved following individual dose titration with oral riociguat, which was generally well tolerated. Further trials in PH have been initiated.
Ghofrani
Hossein-Ardeschir
HA
Department of Internal Medicine, Medical Clinic II/V, University Hospital Giessen and Marburg GmbH, Klinikstrasse 36, 35392 Giessen, Germany. ardeschir.ghofrani@innere.med.uni-giessen.de
Voswinckel
Robert
R
Gall
Henning
H
Schermuly
Ralph
R
Weissmann
Norbert
N
Seeger
Werner
W
Grimminger
Friedrich
F
D000284:Administration, Oral; D004730:Endothelium, Vascular / Q000187:drug effects; D017079:Exercise Tolerance / Q000187:drug effects / Q000502:physiology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors*; D006207:Half-Life; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D011720:Pyrazoles / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D014655:Vascular Resistance / Q000187:drug effects
D011720:Pyrazoles; D011743:Pyrimidines; D006162:Guanylate Cyclase; C542595:riociguat