TABLE 1

Kinetic parameter values from cryopreserved human hepatocytes for midazolam, triazolam, alprazolam, flunitrazepam, and diazepam

Values are means from five donors ± S.D.

Drug
Pathway
(v/Smax)/(v/Smin)a
Vmax
KM or S50b
n
CLintc
nmol/min/106 cells μM ml/min/kg
Midazolam 1′-OH 1.0 0.24 ± 0.12 6.0 ± 4.5
4-OH 1.0 0.18 ± 0.12 44 ± 13 138
Triazolam 1′-OH 5.9 0.11 ± 0.042 42 ± 16
4-OH 8.6 0.28 ± 0.30 210 ± 170 1.2 9.17
Diazepam 3-OH 2.0 0.34 ± 0.29 130 ± 53 1.5
Desmethyl 2.3 0.045 ± 0.031 97 ± 41 5.07
Flunitrazepam 3-OH 1.7 0.14 ± 0.13 66 ± 45 2.1
Desmethyl 3.2 0.019 ± 0.015 43 ± 17 4.19
Alprazolam 1′-OH 7.5 0.024 ± 0.012 170 ± 87 1.7
4-OH
1.4
0.30 ± 0.37
310 ± 230
1.2
1.66

  • ↵ a Measure of autoactivation.

  • ↵ b S50 values shown when autoactivation occurs and n > 1, eq. 1.

  • ↵ c Scaled CLint; see Materials and Methods.