Table 1.

Relative contributions of warfarin enantiomers and metabolites to VKOR antagonism

Inhibitor	Human plasma [1], nM*	IC50, nM	[I]/IC50 × 102 (relative %)
9S-warfarin	1518-2630	25 ± 4.3	10 520 (100)
9R-warfarin	2825-4500	288 ± 80	1562 (14.8)
4′-OH warfarin	ND-69	196 ± 53	35 (0.3)
5-OH warfarin	<2	1145 ± 239	<1 (<0.1)
6-OH warfarin	36-169	434 ± 64	563 (5.4)
7-OH warfarin	392-771	4272 ± 234	18 (<0.1)
8-OH warfarin	<5	>10 000	<1 (<0.1)
10-OH warfarin	52-365	83 ± 10.3	440 (4.2)
Warfarin alcohols	957-1100	132 ± 41	833 (7.9)

The upper range of published circulating levels of VKORC1 inhibitors (plasma [I]) and their F9CH γ-carboxylation inhibitory potentials (IC₅₀) in HEK-C3 cells were used to calculate the relative contributions of each drug to inhibition of VKORC1 activity ([I]/IC₅₀).

^*Wang et al,¹⁵ Chan et al,¹⁶ and Lomonaco et al.¹⁷