Table 2.
Metabolism of ADQ by individual human CYPs.a
| pmol metabolite/mg microsomal protein/min | ||
|---|---|---|
| NADQ | AADQ | |
| HepG2 | 0.74 ± 0.05 | 0.32 ± 0.04 |
| CYP vector | 1.91 ± 0.01 | 0.24 ± 0.08 |
| CYP1A1 | 58.9 ± 1.90* | 54.9 ± 2.10* |
| CYP1A2 | 11.2 ± 0.42* | 0.54 ± 0.01 |
| CYP1B1 | 15.4 ± 0.32* | 13.0 ± 0.71* |
| CYP2A6 | 3.66 ± 0.28* | 0.21 ± 0.02 |
| CYP2A7 | 0.26 ± 0.08 | 0.19 ± 0.01 |
| CYP2A13 | 3.73 ± 0.05* | 0.17 ± 0.01 |
| CYP2B6 | 2.71 ± 0.19* | 0.23 ± 0.04 |
| CYP2C8 | 106 ± 6.90* | 0.27 ± 0.02 |
| CYP2C9 | 0.68 ± 0.04 | 0.25 ± 0.03 |
| CYP2C18 | 2.33 ± 0.13* | 0.24 ± 0.02 |
| CYP2C19 | 11.9 ± 0.32* | 0.17 ± 0.01 |
| CYP2D6 | 7.76 ± 0.37* | 0.39 ± 0.04* |
| CYP2E1 | 3.47 ± 0.11* | 0.19 ± 0.02 |
| CYP3A4 | 29.6 ± 1.90* | 1.05 ± 0.02* |
| CYP3A5 | 14.5 ± 0.75* | 0.79 ± 0.07* |
| CYP3A7 | 2.96 ± 0.12* | 0.20 ± 0.03 |
| CYP4A11 | 0.57 ± 0.13 | 0.16 ± 0.05 |
| CYP4B1 | 0.98 ± 0.13 | 0.15 ± 0.02 |
Metabolism of ADQ by microsomes isolated from HepG2 cells overexpressing human CYPs was assayed in a 125 μl final reaction volume by incubating microsomes (1.0 mg of microsomal protein) with 0.8 mM ADQ, 4 mM MgCl2, 2 mM NADPH, and 100 mM potassium phosphate buffer (pH 7.2) at 37 °C for 30 min with gentle shaking. The metabolites were analyzed using HPLC-MS/MS as described in Materials and Methods. Data are presented as the mean ± standard deviation.
Significantly (p < .05) different from the CYP vector cell line.