Kinetic parameters for CYP3A4 inhibition by ITZ and its metabolites OH-ITZ, keto-ITZ, and ND-ITZ
Ki values were calculated from experiments with heterologously expressed CYP3A4 Supersomes, and IC50 values were determined from inhibition of midazolam hydroxylation in pooled human liver microsomes. The 95% confidence interval for the parameter estimates is presented in brackets.
Ki | Ki,u | IC50 ± S.E. | fu ± S.D. | IC50,u | ||
|---|---|---|---|---|---|---|
| nM | nM | % | nM | |||
| ITZ | 15.7 | 1.3 | 29 ± 10 | 19.6 ± 9.2 | 6.1 | |
| [0-58] | ||||||
| OH-ITZ | 37.8 | 14.4 | 37 ± 13 | 12.4 ± 6.8 | 4.6 | |
| [5-70] | ||||||
| keto-ITZ | NA | NA | 53 ± 17 | 11.7 ± 4.2 | 7.0 | |
| [10-97] | ||||||
| ND-ITZ | NA | NA | 17 ± 6.6 | 2.6 ± 1.2 | 0.44 | |
|
|
|
| [0-34] |
|
| |
NA, not available.