Inhibition of warfarin metabolism by monoclonal antibodies in incubations with human liver microsomes4-a
| Monoclonal Antibody | Antibody | Warfarin | 10-Hydroxywarfarin4-b | 4′-Hydroxywarfarin4-b |
|---|---|---|---|---|
| mg/nmol CYP | % of Control | % of Control | ||
| CYP3A4 | 10–40 | R | <1 | 0–10 |
| CYP3A4 | 10–40 | S | 0–10 | 0–10 |
| CYP3A4 | 10–40 | Racemic | <2 | 0–10 |
| CYP3A4 | 40 | Racemic + quinidine | ∼5 | ∼15 |
| CYP2C9 | 10–40 | R, S, or racemic | ∼100 | ∼100 |
↵4-a Warfarin in methanol was added to human liver microsomes suspended in phosphate buffer (0.1 M, pH 7.4) containing EDTA. The final concentration of warfarin ranged from 50 to 1000 μM. In cases where quinidine was included in incubations, the concentration of quinidine was 50 μM. Human liver microsomes were preincubated with monoclonal anti-CYP IgG for 15 min at room temperature. Reactions were initiated by adding NADPH and proceeded for an additional 30 min.
↵4-b Test incubations were compared with their respective controls containing control ascites.