Riociguat, sold under the brand name Adempas, is a medication by Bayer that is a stimulator of soluble guanylate cyclase (sGC).
A clinical trial testing riociguat for this purpose was prematurely terminated because it increased severe adverse effects and mortality in patients with pulmonary hypertension caused by idiopathic interstitial pneumonia when compared to placebo.
[4] In healthy individuals, nitric oxide (NO) acts as a signaling molecule on vascular smooth muscle cells to induce vasodilation.
NO binds to soluble guanylate cyclase (sGC) and mediates the synthesis of the secondary messenger cyclic guanosine monophosphate (cGMP).
NO also reduces pulmonary smooth muscle cell growth and antagonises platelet inhibition, factors which play a key role in the pathogenesis of PAH.
[12] A phase I study showed that riociguat is rapidly absorbed, and maximum plasma concentration is reached between 0.5 and 1.5 h.[13] The mean elimination half-life appears to be 5–10 hours.
[13] Riociguat plasma concentrations have been also shown to be quite variable between patients, indicating that for clinical use it is probably necessary to titrate the drug specifically for each individual.
[15] Both compounds were tested in various preclinical studies on different animal models and appeared to improve systemic arterial oxygenation.
[9][16] Riociguat was tested in mouse and rat disease models, where it effectively reduced pulmonary hypertension and reversed the associated right heart hypertrophy and ventricular remodelling.
[17] One of the first studies was designed to test the safety profile, pharmacokinetics and pharmacodynamics of single oral doses of riociguat (0.25–5 mg).
[18] In addition, a phase II study of riociguat is underway in patients with other forms of PH such as associated with interstitial lung disease (PH-ILD).
This randomized, double blind, placebo controlled Phase I study investigated the effect of riociguat, administered as 2.5 mg immediate-release (IR)-tablets twice daily over 14 days, on the bone metabolism.