Effect of thalidomide on midazolam 1′- and 4-hydroxylation activities of P450 3A4 and 3A5, and human liver microsomes with the kinetic parameter Ke
Kinetic parameters were calculated with nonlinear regression analysis with S.E. values.
Enzyme | Midazolam Hydroxylation | Vmax | Midazolam | Thalidomide | Goodness of Fit, r2 | ||||
|---|---|---|---|---|---|---|---|---|---|
| Km, μM | Ks, μM | Ki, μM | Ke, μM | ||||||
| nmol/min/nmol P450 | |||||||||
| P450 3A4 | 1′- | 8.6 ± 0.3 | 1.8 ± 0.2 | 87 ± 10 | 850 ± 370 | 0.98 | |||
| 4- | 3.4 ± 0.1 | 25 ± 2 | 1500 ± 620 | 0.99 | |||||
| P450 3A5 | 1′- | 18 ± 1 | 5.5 ± 0.5 | 1100 ± 200 | 40 ± 7 | 0.98 | |||
| 4- | 2.2 ± 0.1 | 59 ± 6 | 160 ± 20 | 0.99 | |||||
| nmol/min/mg protein | |||||||||
| HL-3 microsomes | 1′- | 0.83 ± 0.02 | 3.9 ± 0.3 | 700 ± 100 | 770 ± 300 | 0.98 | |||
| (CYP3A5*3/*3) | 4- | 0.30 ± 0.01 | 52 ± 4 | 850 ± 240 | 0.98 | ||||
| HL-1 microsomes | 1′- | 1.7 ± 0.1 | 12 ± 3 | 670 ± 290 | 62 ± 24 | 0.94 | |||
| (CYP3A5*1/*3) | 4- | 0.35 ± 0.01 | 66 ± 5 |
| 1100 ± 300 |
| 0.94 | ||