Table 1

Ketoconazole inhibition constants (Ki) for the biotransformation of MDZ and TRZ in mouse and human liver microsomes

α-OH-MDZ4-OH-MDZα-OH-TRZ4-OH-TRZ
ModelKiαModelKiModelKiαModelKi
μM μM μM μM
Mousemix1.70  ± 0.593.67  ± 2.14comp0.066  ± 0.014mix0.373  ± 0.1231.09  ± 0.13comp0.076  ± 0.006
Humancomp + K s 0.0054  ± 0.0041comp0.039  ± .006comp0.027  ± 0.0092comp0.047  ± 0.017

The values presented are those that represent the “best-fit” inhibition model and are the mean ± S.D. from two individual animals. Ki model abbreviations: mix, mixed model; comp, competitive model; comp + Ks, competitive model with substrate inhibition. See the text sections for further description of Ki determination.