Rates of covalent binding to protein across species
[3H]-1 (10 μM) was incubated in triplicate with pooled dog, human, rat, or monkey liver microsomes (1 mg protein/ml) for 1 hour at 37°C. Incubations were performed in both the presence and absence of glutathione (5 mM). [3H]Imipramine (10 μM) was also incubated under identical conditions as a positive control.
| Without NADPH | With NADPH | With NADPH and Glutathione | |
|---|---|---|---|
| [3H]daclatasvir (1) | |||
| Human | 15.8 ± 5.0 | 55.2 ± 8.1 | 40.9 ± 7.2 |
| Rat | 13.0 ± 0.1 | 57.6 ± 10.7 | 22.4 ± 3.0 |
| Monkey | 19.6 ± 2.3 | 67.8 ± 21.0 | 25.2 ± 5.8 |
| [3H]Imipramine | |||
| Human | 16.5 ± 1.9 | 218.9 ± 45.6 | 17.1 ± 9.6 |