Table 4: Formation of C-7 and Loss of Substrate in Incubations of [14C]-VNP40101M (25 and 100 µM) with Various Recombinant Human CYP Enzymes (25 pmol/Incubation) Expressed in E. coli (Bactosomes)

Recombinant Human CYP Enzyme Incubation Time (min) [14C]-VNP40101M (µM) C-7 Formed Per Incubation (pmol) [14C]-VNP40101M Detected Per Incubation (pmol) Percent Loss of Substrate (%)1
Bactosome control 10 25 NC 5380 17.9%
Reductase control NC 5390 17.7%
rCYP1A2 NC 5560 15.0%
rCYP2B6 376 5270 19.5%
rCYP2D6 NC 5470 16.5%
Bactosome control 100 NC 20100 14.7%
Reductase control NC 20400 13.6%
rCYP1A2 NC 20300 13.9%
rCYP2B6 513 20000 15.3%
rCYP2D6 NC 20100 14.6%

1 Percent loss of substrate was determined based on the zero-minute microsomal sample. NC: Not calculated (represents a zero or negative value beyond the AUC level). Pmol values are the mean of duplicate determinations and are rounded to three significant figures. Percent values are rounded to one decimal place.