TABLE 3

Kinetic parameters for 16 pathways mediated by CYP3A4, CYP2C9, CYP2C19, and CYP2D6 in HLM and HIM prepared by mucosal scraping


Pathway

Vmax

Km or S50

CLint or CLmax

CLint or CLmaxb

HIM
HLM
HIMa
HLM
HIM
HLM
HIM
HLM
nmol/min/mg protein μM μl/min/mg protein μl/min/pmol P450
1′-Hydroxymidazolam 0.23 ± 0.01 2.7 ± 0.2 10.1 ± 1.6 3.3 ± 0.6 22 895 0.52 5.8
4-Hydroxymidazolam 0.08 ± 0.002 1.3 ± 0.04 22 ± 2 21 ± 2 3.6 59 0.08 0.38
3-Hydroxydiazepam 0.041 ± 0.002 4.5 ± 0.6 213 ± 10 235 ± 54 0.095 11 0.002 0.07
Nordiazepam 0.004 ± 0.0004 0.5 ± 0.05 160 ± 29 132 ± 37 0.01 2.1 0.011 0.15
3-Hydroxyflunitrazepam 0.17 ± 0.02 7.1 ± 0.3 458 ± 47 300 ± 24 0.19 12 0.004 0.08
Desmethylflunitrazepam 0.007 ± 0.001 0.4 ± 0.03 293 ± 60 174 ± 29 0.01 1.4 0.012 0.1
1′-Hydroxyalprazolam 0.004 ± 0.001 0.1 ± 0.05 258 ± 62 274 ± 38 0.006 0.36 0.0002 0.002
4-hydroxyalprazolam 0.036 ± 0.008 3.9 ± 0.4 348 ± 78 309 ± 76 0.05 8.1 0.001 0.05
1′-Hydroxytriazolam 0.061 ± 0.002 2.3 ± 0.5 149 ± 9 80 ± 14 0.2 29 0.005 0.19
4-Hydroxytriazolam 0.12 ± 0.003 2.0 ± 0.6 242 ± 10 92 ± 34 0.25 22 0.006 0.14
Quinidine 0.01 ± 0.001 0.9 ± 0.04 69 ± 19 101 ± 12 0.19 8.7 0.005 0.06
Testosterone 0.26 ± 0.02 6.4 ± 0.3 55 ± 8 56 ± 7 2.7 68.9 0.06 0.44
Nifedipine 0.03 ± 0.003 0.89 ± 0.08 19.7 ± 4.5 10.1 ± 1.8 1.15 88.2 0.03 0.49
Mephenytoin 0.0005 ± 0.00001 0.04 ± 0.0004 106 ± 12 30 ± 1.3 0.0046 1.36 0.005 0.1
Tolbutamide 0.003 ± 0.0001 0.45 ± 0.015 769 ± 124 333 ± 29 0.0037 1.34 0.002 0.06
Bufuralol
0.0007 ± 0.00001
0.09 ± 0.01
5.9 ± 1.2
5.5 ± 1.9
0.12
25.8
0.28
3.2
  • a Values corrected for microsomal binding.

  • b CL data (μl/min/mg) normalized for the population relative abundance for CYP3A4, CYP2C9, CYP2C19, and CYP2D6 in the liver and intestine as shown in Table 2.