Summary of the in vitro parameters describing P450 content and activities
| Patient No. | Specific P450 Content | CYP3A4 | α-Hydroxylation of Midazolam | Apparent Vmax for the Oxidation of Denitronifedipine | Metabolite Formation Rate with 2 μM Methoxyresorufin | ||
|---|---|---|---|---|---|---|---|
| Apparent Vmax | ApparentKM | Goodness of Fit in Eadie-Hofstee Plot (r2) | |||||
| pmol/mg microsomal protein | nmol/100 nmol total P450 | nmol/nmol P450/min | μM | nmol/nmol P450/min | pmol/nmol P450/min | ||
| 1 | 356 | 29.4 | 3.35 | 4.5 | 0.823 | 9.7 | 1693 |
| 2 | 395 | 9.2 | 2.2 | 3.54 | 0.806 | 6.1 | 1693 |
| 3 | 448 | 12.6 | 3.71 | 4.53 | 0.922 | 5.9 (CYP3A5) | 1889 |
| 4 | 295 | 0.5 | 0.9 | 8.32 | 0.901 | 0.5 | 624.3 |
| 5 | 421 | 22 | 4.07 | 6.37 | 0.903 | 4.6 | 1333.3 |
| 6 | 517 | 3.4 | 1.6 | 4 | 0.977 | 2-aND2-a | 1100.5 |
| 7 | 383 | 3.2 | 1.7 | 3.2 | 0.83 | 2.6 | 613.8 |
| 8 | 493 | 8.6 | 2.5 | 5.2 | 0.844 | 7.5 | 1672 |
| 9 | 413 | 10.4 | 1.75 | 2.5 | 0.703 | 4.8 | 920.6 |
| 10 | 412 | 21.2 | 1.84 | 18.07 | 0.797 | 3.1 | 1211.6 |
| 11 | 444 | 16.2 | 1.3 | 13.18 | 0.624 | 5.6 | 841.3 |
| 12 | 275 | 24.2 | 4.81 | 33.4 | 0.833 | 7.7 | 1343.9 |
| 13 | 435 | 61 | 3.06 | 17.6 | 0.725 | 7.1 | 329 |
| 14 | 470 | 17.4 | 3.42 | 22.54 | 0.669 | 4 (CYP3A5) | 709 |
| 15 | ND | 3.8 | ND | ND | ND | ND | |
| 16 | 379 | 8.8 | 1.12 | 6.57 | 0.889 | 1.8 | 1071.4 |
The Western blots showed CYP3A5 expression in the liver samples from patients 3 and 14. Because of insufficient liver tissue, the kinetics for denitronifedipine could not be determined for patient 6. The same was true for both oxidative reactions for patient 15. For correlations among the various parameters, see text.
↵2-a ND, not done.