TABLE 2

Kinetic parameters for diazepam and flunitrazepam metabolite formation in CYP3A4, CYP3A5, and CYP2C19 baculosomes (mean ± S.E.)


Substrate

Pathway

Enzyme

Vmax

Km or Ks

α

β

CLint or CLmax
pmol/min/pmol P450 mM ml/min/nmol P450
Diazepam 3-Hydroxy CYP3A4 5.55 ± 0.21 318 ± 44 0.11 ± 0.03 27.9
CYP3A5 5.77 ± 0.09 339 ± 27 0.025 ± 0.004 54.5
CYP2C19 1.14 ± 0.05 74 ± 6 0.07 ± 0.02 15.3
N-Demethylation CYP3A4 0.67 ± 0.05 157 ± 55 0.28 ± 0.05 4.9
CYP3A5 0.32 ± 0.05 125 ± 45 0.13 ± 0.02 3.8
CYP2C19 1.95 ± 0.13 74 ± 9 0.04 ± 0.02 26.3
Flunitrazepam 3-Hydroxy CYP3A4 1.29 ± 0.05 694 ± 104 0.03 ± 0.01 5.7
CYP3A5 2.38 ± 0.05 337 ± 32 0.07 ± 0.02 13.4
CYP2C19 0.064 ± 0.003 89 ± 13 0.72
N-Demethylation CYP3A4 0.20 ± 0.01 224 ± 44 0.36 ± 0.19 0.9
CYP3A5 0.14 ± 0.01 128 ± 21 1.09


CYP2C19
0.50 ± 0.07
289 ± 48

0.28 ± 0.10
1.7