TABLE 2

Effects of inhibitors on the steady-state kinetics of 7BQ debenzylation by CYP3A4


Inhibitor

Ki,app

Concentration of Inhibitor Used

S0.5 for 7BQ

nH for 7BQ
Control
Inhibitor
Control
Inhibitor
μM μM
Bromocriptine 0.14 5.33 40 ± 1.7 172 ± 6 1.85 ± 0.07 3.7 ± 0.2
Cyclosporin A 0.6 84 43 ± 1.7 159 ± 5 1.7 ± 0.05 2.7 ± 0.15
Erythromycin 27 1000 40 ± 1.7 104 ± 8 1.85 ± 0.07 2.8 ± 0.24
Troleandomycin 4.9 246 40 ± 1.7 107 ± 6 1.85 ± 0.07 2.3 ± 0.1
Ketoconazole 0.02 0.75 39 ± 1.6 139 ± 3 1.67 ± 0.05 2.7 ± 0.12
Diltiazem 11 500 39 ± 1.5 95 ± 9 1.73 ± 0.05 2.1 ± 0.17
Midazolam 6.4 45 39 ± 1.6 106 ± 16 1.67 ± 0.05 1.3 ± 0.12
Testosterone
N.D.
500
50 ± 4
51 ± 7
1.6 ± 0.08
1 ± 0.1
  • N.D., not determined because of activation of 7BQ debenzylation seen at some testosterone concentrations.