Warfarin pharmacodynamics and pharmacokinetics are not affected by the soluble guanylate cyclase stimulator riociguat (BAY 63-2521)

Table 1 Pharmacokinetic and clotting profile parameter ratios of least squares means for warfarin and riociguat

Ratios	Analyte	Parameter	Ratio (90% CI)
(Warfarin + riociguat)/(warfarin + placebo)	R-warfarin	AUC (μg.h/L)	1.01 (0.96–1.05)
		C_max (μg/L)	1.02 (0.96–1.08)
	S-warfarin	AUC (μg.h/L)	1.01 (0.97–1.04)
		C_max (μg/L)	1.01 (0.95–1.09)
	Prothrombin time	AUC_(0–96) (s.h)	0.99 (0.97–1.01)
	Factor VII % clotting activity	AUC_(0–96) (%.h)	1.03 (1.00–1.06)
(Warfarin + riociguat)/riociguat	Riociguat	AUC_τ,ss (μg.h/L)	0.96 (0.87–1.06)
		C_max,SS (μg/L)	0.84 (0.70–1.01)

AUC, area under the plasma concentration-time curve from zero to infinity after single dose administration; AUC_τ,ss, AUC at steady state; AUC_(0–96), AUC from zero to 96 h after administration of warfarin; CI, confidence interval; C_max, maximum drug concentration in plasma after single dose administration; C_max,SS, C_max at steady state.