Relative activity factor estimates for major human cytochrome P450 enzymes in human liver microsomes
Intrinsic clearance values and relative activity factors, determined using the drug depletion method, are compared with literature Vmax/Km ratios from enzyme kinetic studies (Walsky and Obach, 2004). Data are the mean and S.D. of intrinsic clearance values for 16 individual human liver microsome donors. Values for each donor were measured in triplicate.
Compound | Enzyme | Current Study | Literature Vmax/Km | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| HLM CLint | P450 CLint | RAF | HLM CLint | P450 CLint | RAF | ||||||
| μl/min/mg | μl/min/pmol | pmol/mg | μl/min/mg | μl/min/pmol | pmol/mg | ||||||
| Phenacetin | CYP1A2 | 27 ± 20 | 4.9 ± 0.3 | 5.6 ± 4.1 | 15 | 1.9 | 8 | ||||
| Diclofenac | CYP2C9 | 487 ± 262 | 24 ± 1 | 20 ± 11 | 418 | 25 | 17 | ||||
| Midazolam | CYP3A4 | 1073 ± 860 | 23 ± 3 | 47 ± 37 | 537 | 26 | 21 | ||||
| Bufuralol | CYP2D6 | 93 ± 58 | 27 ± 6 | 3.4 ± 2.1 | N.A. | N.A. | N.A. | ||||
| Mephenytoin | CYP2C19 | N.T. | N.T. | N.T. | 1.0 | 0.5 | 2 | ||||
N.A., not available; N.T., not tested.