Table 5: 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 Insect Cells (Supersomes).

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
Insect cell control 10 25 NC 5440 17.0%
rCYP2A6 + b5 2 NC 6490 2 8.0% 2
rCYP2C8 + b5 NC 5440 16.9%
rCYP2C9 + b5 NC 5470 16.5%
rCYP2C19 + b5 NC 5390 17.6%
rCYP3A4 + b5 362 5150 21.3%
Insect cell control 100 NC 20100 14.6%
rCYP2C8 + b5 NC 19600 16.8%
rCYP2A6 + b5 2 NC 21600 2 7.4% 2
rCYP2C9 + b5 NC 19900 15.6%
rCYP2C19 + b5 NC 19400 17.5%
rCYP3A4 + b5 549 18700 20.4%

1 Percent loss of substrate was determined based on the zero-minute microsomal sample.
2 rCYP2A6 incubations were performed as a separate experiment. 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 with the exception of values at or above 100% which are rounded to three significant figures.