TABLE 4.
The fractions of warfarin metabolic clearance by each metabolic pathway Fraction values are calculated based on literature (Cheng et al., 2022b). The metabolic fractions presented in the original study for each parent compound were summed and rescaled to 100% to calculate the new fractions of hepatic intrinsic CL mediated by the various metabolic pathways. The key assumption of this approach is to assume the metabolism of S- or R-warfarin is totally mediated by the respective five metabolic pathways.
| S-Warfarin | CYP2C9 *1/*1 | CYP2C9 *1B/*1B | CYP2C9 *1/*3 | CYP2C9 *2/*3 | CYP2C9 *3/*3 |
|---|---|---|---|---|---|
| 4’-OH (%) | 2.8 | 2.9 | 4.7 | 10.4 | 28.2 |
| 6-OH (%) | 19.8 | 16.8 | 20.1 | 17.6 | 20.6 |
| 7-OH (%) | 75.3 | 78.4 | 72.6 | 68.5 | 42.5 |
| 8-OH (%) | 1.5 | 1.2 | 1.7 | 1.9 | 4.8 |
| 10-OH (%) | 0.6 | 0.7 | 0.9 | 1.5 | 4.0 |
| R-Warfarin | CYP2C9 *1/*1 | CYP2C9 *1B/*1B | CYP2C9 *1/*3 | CYP2C9 *2/*3 | CYP2C9 *3/*3 |
| 4’-OH (%) | 2.8 | 3.3 | 1.8 | 1.8 | 1.8 |
| 6-OH (%) | 61.1 | 72.5 | 61.7 | 61.7 | 61.7 |
| 7-OH (%) | 9.8 | 11.7 | 9.9 | 9.9 | 9.9 |
| 8-OH (%) | 23.5 | 9.2 | 23.8 | 23.8 | 23.8 |
| 10-OH (%) | 2.8 | 3.3 | 2.8 | 2.8 | 2.8 |