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) |
| 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