Pharmacokinetics of the soluble guanylate cyclase stimulator riociguat in individuals with hepatic impairment
© Frey et al; licensee BioMed Central Ltd. 2013
Published: 29 August 2013
Riociguat is the first oral, soluble guanylate cyclase stimulator currently under review for the treatment of pulmonary hypertension (PH), a progressive disease with high mortality [1–7]. The present pooled analysis assessed the pharmacokinetics of riociguat and its metabolite M1 (BAY 60-4552) in individuals with hepatic impairment (Child–Pugh A or B) and healthy controls. The safety and tolerability of riociguat were evaluated.
Two non-randomized, non-blinded, observational studies with group stratification were included in the analysis. The studies were conducted in a single centre in Germany, in accordance with Good Clinical Practice and industry guidelines [8, 9]. Individuals with liver cirrhosis (Child–Pugh A, n = 16; Child–Pugh B, n = 16) and 32 healthy age-, weight- and sex-matched volunteers received a single oral tablet dose of riociguat 1 mg. Dense sampling was performed for pharmacokinetic parameters.
Pharmacokinetic parameters of riociguat in plasma following a single oral dose of riociguat 1 mg
Child–Pugh A (n = 16)
Child–Pugh B (n = 16)
Control A (n = 16)
Control B (n = 16)
Child–Pugh A individuals had similar plasma riociguat concentrations to controls. Child–Pugh B individuals had a higher exposure to riociguat than those in the other groups; particular care should be exercised during individual dose titration in patients with moderate hepatic impairment.
The studies were funded by Bayer Pharma AG, Wuppertal, Germany, and performed by Atef Halabi, Clinical Trial Director, CRS Clinical Research Services Kiel GmbH, Lornsenstrasse 7, 24105 Kiel, Germany.
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