TABLE 2

Kinetic parameters for methadone N-demethylation

Results are the parameter estimate ± standard error of the estimate.

ParameterCYP2B6.1CYP2B6.4CYP2B6.5CYP2B6.6CYP2B6.9
R-EDDP formationS-EDDP formationR-EDDP formationS-EDDP formationR-EDDP formationS-EDDP formationR-EDDP formationS-EDDP formationR-EDDP formationS-EDDP formation
CYP2B6 + P450 reductase + cytochrome b5
Vmax (pmol/min per picomole P450)11 ± 19 ± 119 ± 1*8 ± 1*22 ± 4*13 ± 54 ± 3*2 ± 1*7 ± 46 ± 4
Km (μM)87 ± 448 ± 6148 ± 6*34 ± 3*284 ± 73*138 ± 78337 ± 29054 ± 46298 ± 20492 ± 91
Clint (ml/min per nanomole)0.13 ± 0.010.19 ± 0.030.13 ± 0.010.23 ± 0.020.08 ± 0.030.09 ± 0.060.01 ± 0.01*0.04 ± 0.04*0.02 ± 0.02*0.07 ± 0.08
CYP2B6 + P450 reductase
Vmax (pmol/min per picomole P450)5 ± 14 ± 19 ± 1*7 ± 1*5 ± 15 ± 12 ± 1*4 ± 23 ± 1*4 ± 2
Km (μM)52 ± 333 ± 887 ± 3*43 ± 5119 ± 33*67 ± 4596 ± 3267 ± 44132 ± 32*65 ± 36
Clint (ml/min per nanomole)0.10 ± 0.010.12 ± 0.040.11 ± 0.010.16 ± 0.020.04 ± 0.01*0.07 ± 0.060.02 ± 0.01*0.06 ± 0.050.02 ± 0.01*0.06 ± 0.04
  • * Significantly different versus CYP2B6.1 (P < 0.05)