Table 3.
Preferred model mechanism and parameters for steady-state glucuronidation of R- and S-7-hydroxywarfarin by HLM150a
| Substrate | Metabolitesb | Modelc | Parameters for Preferred Model | |||
|---|---|---|---|---|---|---|
| Vmax1d | Vmax2d | Ks (μM) | Kss (μM) | |||
| R-7-HOWAR | 7-HOWAR-4-GLUC | Substrate Inhibition | 58.0 (49.5–66.1) | 19.0 (16.3–21.4) | 145 (112–183) | 145 (112–183) |
| 7-HOWAR-7-GLUC | Michaelis-Menten | 1090 (1050–1140) | - | 121 (101–144) | - | |
| S-7-OHWAR | 7-HOWAR-4-GLUC | Substrate Inhibition | 19.7 (17.6–22.4) | - | 110 (83.0–149) | 2850 (1950–4400) |
| 7-HOWAR-7-GLUC | Substrate Inhibition | 1470 (1020–2700) | - | 927 (559–1960) | 1310 (538–2810) | |
The nonsymmetrical 95 % confidence intervals for parameters are shown in parentheses.
Glucuronidation resulted in conjugation of the hydroxyl group at either the C4 or C7 position resulting in the formation of 7-HOWAR-4-GLUC or 7-HOWAR-7-GLUC, respectively, as described in the Discussion.
See Table 3 for details for the specific metabolic mechanism describing formation of the respective glucuronides metabolites.
Units are nmol/min/mg protein.