Kinetic parameters for the in vitro effect of various CYP3A4 substrates on midazolam in human lymphoblast-expressed CYP3A4, generated by multisite kinetic model approach (mean ± S.E.) The kinetic parameters were determined using multisite kinetic models (n = 20-30) defined in footnotes a and b.
CYP3A4 Modifier | Vmax | Ks | Ki | γ | δ |
|---|---|---|---|---|---|
| pmol/min/pmol P450 | μM | μM | |||
| NIFa | 2.8±0.1 | 4.1±0.7 | 13.4±3.2 | 0.2±0.1 | 1.4±0.3 |
| FELa | 4.2±0.1 | 3.1±0.3 | 10.1±1.9 | 0.4±0.1 | 3.6±1.1 |
|
TSTb
|
5.3±0.1
|
5.1±0.3
|
139±26
|
|
2.2±0.6
|
↵ a Equation 1, α1 (cooperative binding of the modifier) = 0.24 and 0.9 for FEL and NIF, respectively
↵ b Equation 5, three-site model with distinct substrate-binding sites, Ks2 (4-OH MDZ) = 8.56 ± 0.25 μM. Ks in the Table refers to the Ks1 (1′-OH MDZ), α defining cooperative binding of TST = 0.25±0.04