Warfarin pharmacodynamics and pharmacokinetics are not affected by the soluble guanylate cyclase stimulator riociguat (BAY 63-2521)
© Frey et al; licensee BioMed Central Ltd. 2009
Published: 11 August 2009
Pulmonary hypertension (PH) is a progressive and debilitating condition with a high rate of mortality. Riociguat (BAY 63-2521) is a new drug in development for PH that is well tolerated [1, 2] and has superior efficacy to nitric oxide in patients with PH . Treatment recommendations for PH are based on combination therapies that include warfarin. The aim of this study was to investigate potential pharmacodynamic or pharmacokinetic interactions of riociguat and warfarin.
Materials and methods
This single-centre, randomized, double-blind, placebo-controlled, crossover, interaction study included healthy male volunteers aged 18–45 years. Riociguat (2.5 mg) or placebo was administered orally three times daily (t.i.d.) for 10 days. Warfarin sodium (25 mg) was administered as a single oral dose 21 days before the study and on the 7th day of treatment with riociguat or placebo.
Pharmacokinetic and clotting profile parameter ratios of least squares means for warfarin and riociguat
Ratio (90% CI)
(Warfarin + riociguat)/(warfarin + placebo)
Factor VII % clotting activity
(Warfarin + riociguat)/riociguat
A single dose of warfarin was administered on day 7. Doses of riociguat or placebo were administered three times daily on days 1–10. Geometric means are shown, with upward bars denoting geometric means*geometric standard deviations and downward bars denoting geometric means/geometric standard deviations.
The combined use of riociguat with warfarin had a favourable safety profile. Riociguat at a dose of 2.5 mg t.i.d. demonstrated no pharmacodynamic interactions and no clinically relevant pharmacokinetic interactions with warfarin. Thus, the combined use of riociguat with warfarin is not expected to represent a risk and no dose adaptation is required.
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