Table 3.
Kinetic parameters of MODF formation in human liver microsomes and cDNA-expressed CYPs
| Enzyme activity CYP2D6 (pmol min−1 mg−1) | CYP1A2 (pmol min−1 mg−1) | Km (µM) | Vmax (pmol min−1 mg−1 or nmol−1 CYP) | CLint (µl min−1 mg−1 or nmol−1 CYP) | |
|---|---|---|---|---|---|
| Pooled microsome | 81 | 540 | High-affinity component | ||
| 4.0 (0.7, 7.3) | 1.0 (0.7, 1.3) | 0.252 | |||
| Low-affinity component | |||||
| 673.1 (547.2, 799.0) | 14.0 (13.1, 14.9) | 0.021 | |||
| Microsomes containing cDNA-expressed CYP | |||||
| CYP1A2 | – | – | 587.9 (411.8, 764.0) | 34.4 (29.6, 39.2) | 0.058 |
| CYP2D6.1 | – | – | 2.8 (1.9, 3.6) | 19.5 (18.3, 20.7) | 7.063 |
| CYP2D6.10 | – | – | 8.2 (5.3, 11.0) | 2.9 (2.6, 3.1) | 0.352 |
| Single-donor microsome from CYP2D6 PMs | |||||
| HH31 | 4.1 | 2900 | 220.2 (206.9, 233.5) | 69.6 (68.2, 71.0) | 0.316 |
| HH35 | 0.4 | 240 | 504.5 (462.9, 546.1) | 8.2 (7.9, 8.5) | 0.016 |
| HH61 | 0.7 | 31 | 2186.4 (1653.4, 2719.3) | 6.0 (4.9, 7.0) | 0.003 |
Results are presented as value (95% CI). Enzyme activities of CYP2D6 and CYP1A2 are presented as activities of bufuralol 1′-hydroxylase and phenacetin O-deethylase, respectively. Vmax and CLint are expressed as per mg protein for human liver microsomes or per nmol CYP for microsomes containing cDNA-expressed CYP.