Table 1

Constants of inhibition (K i) and type of inhibition on CYP1B1 activity of various anticancer agents and compounds are shown

Inhibition TypeKi Mean ± S.D. (n ≥ 3)
μM
Anticancer agents
 FlutamideCompetitive1.0  ± 0.1
 MitoxantroneCompetitive11.6  ± 0.1
 PaclitaxelCompetitive31.6  ± 9.4
 DocetaxelCompetitive28.0  ± 9.8
 TamoxifenNoncompetitive5.0  ± 0.1
 DoxorubicinMixed2.6  ± 0.2
 DaunomycinMixed2.1  ± 0.1
 5-Fluorouracil (100 μM)No inhibition
 Etoposide (100 μM)No inhibition
 Cyclophosphamide (100 μM)No inhibition
 Vinblastine (100 μM)No inhibition
 Vincristine (100 μM)No inhibition
Other compounds
 EstradiolCompetitive1.9  ± 0.1
 TestosteroneCompetitive411.8  ± 40.4
 α-NaphthoflavoneNoncompetitive0.0028  ± 0.0005
 KetoconazoleNoncompetitive0.3  ± 0.1
 Cyclosporine (100 μM)No inhibition
 Erythromycin (100 μM)No inhibition

CYP1B1 activity was measured by the O-deethylation of ethoxyresorufin (EROD) and K i values were determined as the mean of ≥3 values, by Dixon plots of the velocity data. Type of inhibition was determined by Dixon and Cornish-Bowden plots. The maximum concentration evaluated is indicated in parentheses for compounds with no apparent CYP1B1 interaction.