Clinical Pharmacokinetic and Pharmacodynamic Profile of Riociguat

Clinical Pharmacokinetics
Reiner FreyWolfgang Mück

Abstract

Oral riociguat is a soluble guanylate cyclase (sGC) stimulator that targets the nitric oxide (NO)-sGC-cyclic guanosine monophosphate pathway with a dual mode of action: directly by stimulating sGC, and indirectly by increasing the sensitivity of sGC to NO. It is rapidly absorbed, displays almost complete bioavailability (94.3%), and can be taken with or without food and as crushed or whole tablets. Riociguat exposure shows pronounced interindividual (60%) and low intraindividual (30%) variability in patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH), and is therefore administered using an individual dose-adjustment scheme at treatment initiation. The half-life of riociguat is approximately 12 h in patients and approximately 7 h in healthy individuals. Riociguat and its metabolites are excreted via both renal (33-45%) and biliary routes (48-59%), and dose adjustment should be performed with particular care in patients with moderate hepatic impairment or mild to severe renal impairment (no data exist for patients with severe hepatic impairment). The pharmacodynamic effects of riociguat reflect the action of a vasodilatory agent, and the hemodynamic response to riociguat co...Continue Reading

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Citations

Jun 18, 2019·Basic & Clinical Pharmacology & Toxicology·Anne Kathrine ToxvigMarcus Krüger
Sep 10, 2019·Hypertension·Michel AziziJean-Sébastien Hulot
Oct 18, 2019·Expert Opinion on Drug Metabolism & Toxicology·Natalia A JungmannMichael Gerisch
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Jan 20, 2021·Respiratory Medicine·Hossein-Ardeschir GhofraniGérald Simonneau
Apr 13, 2021·Frontiers in Medicine·Mazen Al-QadiH James Ford
Jun 28, 2019·Molecular Pharmaceutics·D Chase PectolSoon-Mi Lim
Oct 3, 2021·British Journal of Pharmacology·Peter SandnerJohannes-Peter Stasch

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Methods Mentioned

BETA
contraception
pharmacotherapy

Clinical Trials Mentioned

NCT00454558
NCT00680654
NCT02556268

Software Mentioned

PATENT
RESPITE
PATENT PLUS

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