Substrates | Parameters | hCYP3A4 | hCYP3A5 | pCYP3A22 | pCYP3A29 | pCYP3A46 | HLM | PLM |
---|---|---|---|---|---|---|---|---|
Testosterone | Vmax (nmol/min per nmol P450) | 6.79 ± 0.16 | 1.33 ± 0.05 | 3.52 ± 0.11###§§§ | 5.97 ± 0.12##§§§ | 0.83 ± 0.03###§§§ | 3.67 ± 0.07 | 2.96 ± 0.16** |
S50 (µM) | 112.2 ± 6.4 | 136.2 ± 10.4 | 87.8 ± 7.4#§§§ | 89.0 ± 4.6##§§§ | 146.9 ± 11.9## | 77.5 ± 3.5 | 107.5 ± 16.9* | |
CLint (μl/min per nmol P450) | 60.5 | 9.8 | 40.1 | 67.2 | 5.6 | 47.3 | 27.5 | |
n | 1.23 ± 0.07 | 1.48 ± 0.13 | 0.98 ± 0.06 | 1.12 ± 0.05 | 1.23 ± 0.09 | 1.51 ± 0.10 | 0.82 ± 0.08 | |
r | 0.9967 | 0.9921 | 0.9949 | 0.9973 | 0.9949 | 0.9912 | 0.9847 | |
Midazolam | Vmax (nmol/min per nmol P450) | 1.07 ± 0.01 | 2.84 ± 0.04 | 0.30 ± 0###§§§ | 0.49 ± 0.02###§§§ | 0.37 ± 0.01###§§§ | 7.98 ± 0.21 | 3.19 ± 0.09*** |
S50 (µM) | 3.0 ± 0.1 | 5.9 ± 0.2 | 5.7 ± 0.02###§ | 16.2 ± 0.04###§§§ | 19.4 ± 0.07###§§§ | 9.0 ± 0.7 | 22.4 ± 1.6*** | |
CLint (μl/min per nmol P450) | 360.9 | 480.3 | 52.3 | 30.6 | 18.9 | 891.1 | 142.4 | |
n | 1.14 ± 0.03 | 1.04 ± 0.03 | 0.98 ± 0.17 | 1.03 ± 0.04 | 1.26 ± 0.07 | 0.92 ± 0.04 | 1.17 ± 0.07 | |
r | 0.9989 | 0.9993 | 0.9997 | 0.9987 | 0.9971 | 0.9978 | 0.9923 | |
Nifedipine | Vmax (nmol/min per nmol P450) | 1.46 ± 0.04 | 1.95 ± 0.06 | 1.05 ± 0.03###§§§ | 1.67 ± 0.02###§§§ | 1.20 ± 0.05##§§§ | 1.93 ± 0.05 | 4.18 ± 0.21*** |
S50 (µM) | 12.6 ± 0.9 | 28.5 ± 2.2 | 28.5 ± 2.7### | 31.2 ± 0.7### | 63.0 ± 6.4###§§§ | 17.5 ± 1.3 | 34.7 ± 4.5** | |
CLint (μl/min per nmol P450) | 115.6 | 68.5 | 36.9 | 53.3 | 19.0 | 109.9 | 120.3 | |
n | 1.10 ± 0.07 | 1.12 ± 0.06 | 0.90 ± 0.04 | 1.21 ± 0.02 | 0.92 ± 0.03 | 1.10 ± 0.07 | 1.02 ± 0.08 | |
r | 0.9957 | 0.9978 | 0.9983 | 0.9997 | 0.9990 | 0.9933 | 0.9918 |
n, Hill coefficient; r, regression coefficient.
Statistically significant difference compared with HLM (*P < 0.05; **P < 0.01; ***P < 0.001).
Statistically significant difference compared with hCYP3A4 (#P < 0.05; ##P < 0.01; ###P < 0.001).
Statistically significant difference compared with hCYP3A5 (§P < 0.05; §§P < 0.01; §§§P < 0.001).