Mean (±S.D.) intrinsic clearance of (R)- and (S)-metoprolol in pooled human liver microsomes in the absence and in the presence of 0.5, 1, and 2 μM paroxetine (total added concentrations) (substrate depletion experiments; three independent determinations)
| Paroxetine3-a | CLint | (R)/(S)-Ratio | ||
|---|---|---|---|---|
| Total | Unbound | (R)-Metoprolol | (S)-Metoprolol | |
| μM | μl/min/mg | |||
| 0 | 0 | 3.94 ± 0.56 | 2.54 ± 0.23 | 1.55 ± 0.16 |
| 0.5 | 0.04 | 2.24 ± 0.32 | 1.89 ± 0.52 | 1.25 ± 0.43 |
| 1 | 0.08 | 1.57 ± 0.31 | 1.48 ± 0.12 | 1.07 ± 0.27 |
| 2 | 0.16 | 1.15 ± 0.20 | 1.22 ± 0.20 | 0.98 ± 0.31 |
↵3-a Taking into account nonspecific microsomal binding, with fu,mic = 0.08 at 2 mg/ml microsomal protein, used in these experiments.