Kinetic parameters for 1"-hydroxylation of BF enantiomers by human liver microsomes and recombinant P450 enzymes
| Km1(μM) | Vmax12-a | CL12-b(Vmax/Km) | Km2(μM) | Vmax22-a | CL22-b(Vmax/Km) | |
|---|---|---|---|---|---|---|
| Human liver microsomes2-c | ||||||
| 1"R-OH-R-BF | 4.20 ± 1.37 | 0.30 ± 0.15 | 0.08 ± 0.07 | 21.1 ± 0.70 | 0.31 ± 0.20 | 0.014 ± 0.009 |
| 1"S-OH-R-BF | 4.25 ± 1.74 | 1.54 ± 0.95 | 0.44 ± 0.40 | |||
| 1"R-OH-S-BF | 5.53 ± 1.54 | 0.22 ± 0.14 | 0.04 ± 0.01 | 51.0 ± 37.9 | 0.35 ± 0.25 | 0.007 ± 0.004 |
| 1"S-OH-S-BF | 4.46 ± 0.83 | 0.59 ± 0.34 | 0.13 ± 0.08 | |||
| Human liver microsomes (HLM-059) | ||||||
| 1"R-OH-R-BF | 3.83 | 0.40 | 0.104 | 128 | 2.28 | 0.018 |
| 1"S-OH-R-BF | 4.10 | 0.26 | 0.063 | 42.2 | 0.53 | 0.013 |
| 1"R-OH-S-BF | 11.6 | 0.44 | 0.034 | 115 | 1.32 | 0.012 |
| 1"S-OH-S-BF | 12.4 | 0.29 | 0.023 | 32.9 | 0.14 | 0.004 |
| Recombinant CYP2D6 | ||||||
| 1"R-OH-R-BF | 2.40 | 7.58 (50.0)2-d | 3.16 (20.8)2-e | |||
| 1"S-OH-R-BF | 2.20 | 30.0 (200) | 13.8 (90.9) | |||
| 1"R-OH-S-BF | 2.36 | 1.55 (10.0) | 0.66 (4.33) | |||
| 1"S-OH-S-BF | 2.48 | 3.44 (22.7) | 1.39 (9.18) | |||
| Recombinant CYP2C19 | ||||||
| 1"R-OH-R-BF | 27.2 | 10.3 (21.7) | 0.38 (0.80) | |||
| 1"S-OH-R-BF | 18.0 | 1.67 (3.50) | 0.09 (0.19) | |||
| 1"R-OH-S-BF | 18.0 | 11.3 (23.8) | 0.63 (1.32) | |||
| 1"S-OH-S-BF | 16.0 | 2.74 (5.75) | 0.17 (0.35) | |||
| Recombinant CYP1A2 | ||||||
| 1"R-OH-R-BF | 41.6 | 0.92 (4.48) | 0.02 (0.11) | |||
| 1"S-OH-R-BF | 49.7 | 2.29 (11.2) | 0.05 (0.23) | |||
| 1"R-OH-S-BF | 55.8 | 1.28 (6.25) | 0.02 (0.11) | |||
| 1"S-OH-S-BF | 64.4 | 2.02 (9.90) | 0.03 (0.15) | |||
| Recombinant CYP3A4 | ||||||
| 1"R-OH-R-BF | 64.5 | 0.37 (4.07) | 0.01 (0.06) | |||
| 1"S-OH-R-BF | 48.5 | 0.84 (5.32) | 0.02 (0.11) | |||
| 1"R-OH-S-BF | 176.2 | 0.74 (4.65) | 0.01 (0.03) | |||
| 1"S-OH-S-BF | 78.4 | 0.78 (4.93) | 0.01 (0.06) | |||
↵2-a Values are nmol/min/mg protein.
↵2-b Values are ml/min/mg protein.
↵2-c Values are the mean ± S.D. (n = 3, HLM-003, HLM-014, and HLM-086).
↵2-d Values in parentheses are calculated, expressed in terms of nmol/min/nmol P450.
↵2-e Values are ml/min/nmol P450. The values for HLM-059 and recombinant P450 enzymes were the means of duplicate determinations.