Kinetic parameters for the in vitro effect of various CYP3A4 substrates on NIF/FEL in human lymphoblast-expressed CYP3A4, generated by multisite kinetic model approach (mean ± S.E.) The kinetic parameters were determined using generic two-site model (n = 20-30) defined in footnotes a, b, and c.
Substrate | CYP3A4 Modifier | Vmax | Ks | Ki | γ | δ |
|---|---|---|---|---|---|---|
| pmol/min/pmol P450 | μM | μM | ||||
| Nifedipinea | MDZ | 6.5±0.1 | 19.4±1.5 | 20.8±4.1 | 0.45±0.10 | 0.95±0.11 |
| FEL | 10.1±0.2 | 36.3±1.7 | 16.6±3.7 | 0.56±0.09 | 0.62±0.09 | |
| Felodipine | MDZb | 13.8±0.5 | 46.2±4.3 | 198±41 | 0.81±0.11 | 0.22±0.04 |
|
|
NIFc
|
16.5±0.4
|
34.8±2.0
|
33.1±8.0
|
|
2.1±0.1
|
↵ a Equation 3, β (Kp from SES) = 0.41±0.10 (MDZ) and 0.44±0.09 (NIF)
↵ b Equation 2 (Galetin et al., 2002), β = 2 as Vmax is equivalent to 2Kp[E]t, where [E]t is the total enzyme concentration (Segel, 1975)
↵ c Partial inhibition model defined by eq. 2 was applied