Effect of erythromycin on the kinetic parameters for midazolam and diltiazem metabolism by CYP3A4
As described under Materials and Methods, the incubation time for the kinetic experiments was selected to avoid any complications from the reported inactivation of the enzyme by midazolam (Khan et al., 2002) or diltiazem (Jones et al., 1999).
Reaction | S0.5 | Vmax | nH | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Control | +Inhibitor | Control | +Inhibitor | Control | +Inhibitor | ||||
| μM | min-1 | ||||||||
| Midazolam 1′-hydroxylation | 6.2 ± 1.4 | 25.9 ± 1.6 | 3.80 ± 0.39 | 1.63 ± 0.07 | 0.94 ± 0.07 | 1.54 ± 0.08 | |||
| Midazolam 4-hydroxylation | 23.5 ± 6.3 | 103 ± 31 | 2.25 ± 0.25 | 2.75 ± 0.76 | 0.88 ± 0.07 | 1.45 ± 0.09 | |||
| Diltiazem N-demethylation | 38.2 ± 2.5 | 552 ± 337 | 83.8 ± 1.9 | 126 ± 43 | 0.83 ± 0.03 | 0.90 ± 0.10 | |||