Table 1.

Enzyme kinetic variables for CYP3A4-, CYP3A5-, CYP2D6-, CYP1A1-, and CYP1A2-mediated metabolism of gefitinib and erlotinib

CYP3A4CYP3A5CYP2D6CYP1A1CYP1A2
Disappearance of gefitinib*
    Vmax (nmol/min/nmol CYP)20.8 (5.9%)28.0 (11.1%)21.7 (13.1%)19.2 (4.9%)ND
    S50 (μmol/L)25.7 (8.5%)43.7 (20.3%)24.7 (28.5%)24.5 (23.5%)ND
    n2.05 (12.8%)1.26 (9.9%)9.91 (35.4%)10.0 (30.1%)ND
    Clmax (mL/min/nmol CYP)0.410.390.630.57ND
Disappearance of erlotinib*
    Vmax (nmol/min/nmol CYP)4.17 (5.2%)4.49 (4.1%)4.08 (15.6%)3.99 (8.1%)4.61 (5.5%)
    S50 (μmol/L)9.0 (9.7%)11.8 (8.4%)26.9 (25.5%)7.09 (17.8%)15.4 (8.4%)
    n1.68 (11.9%)1.40 (7.4%)1.44 (14.2%)3.38 (54.5%)1.93 (10.7%)
    Clmax (mL/min/nmol CYP)0.240.210.080.310.15
Formation of OSI-420
    Vmax (nmol/min/nmol P450)0.14 (22.6%)0.36 (46.0%)0.43 (6.2%)0.29 (17.9%)0.27 (14.4%)
    Km (μmol/L)1.74 (71.8%)9.50 (66.5%)10.2 (17.1%)13.5 (56.8%)8.96 (44.3%)
    Clint2 (mL/min/nmol P450)0.010.01
    Clint (mL/min/nmol P450)§0.090.050.040.020.03
  • NOTE: Data are the variable estimates and the coefficient of variation of the estimate is provided in parentheses. ND indicates that gefitinib was metabolized by CYP1A2 to a negligible extent.

    Abbreviation: ND, not determined.

  • * Kinetic variables were obtained from the fittings of pooled data from two or three experiments to the Hill equation.

  • Calculated from Eq. D.

  • Kinetic variables were obtained from the fittings of pooled data from two or three experiments to the one or two Michaelis-Menten function.

  • § Calculated from Eq. E.