Compound | Incubations with Hepatocyte Suspensions | Incubations with Hepatocyte Cultures | |||||||
---|---|---|---|---|---|---|---|---|---|
Human (Donor 1) without 1-ABTa | Human (Donor 2) | Human (Donor 3) | Human (Donor 4) | Human (Donor 5) | Wistar Rat (Male) | Cynomolgus Monkey (Male) | |||
Without 1-ABT | With 1-ABT | Without 1-ABT | With 1-ABT | ||||||
%total chromatogram radioactivity | |||||||||
M1 | 1.6 | 1.2 | 1.3 | 1.4 | 1.7 | 4.2 | 8.9 | 2.9 | 1.9 |
M5 | —b | — | 2.5 | ||||||
M6 | 1.3 | ||||||||
M7 | ✓c | 2.4 | ✓ | ||||||
M2 | ✓ | ✓ | ✓ | 1.1 | 1.2 | 4.4 | 6.8 | ||
M8 | 12.1 | 7.3 | |||||||
M3 | 9.6 | 10.8 | 11.7 | 9.0 | 9.1 | 11.3 | 24.9 | ||
M4 | ✓ | 1.1 | 1.2 | 1.6 | 1.3 | 6.8 | 6.1 | 30.1 | 9 |
M9 | 1.3 | ||||||||
M10 | 2.3 | ||||||||
M11 | 3.1 | 1.1 | |||||||
M12 | 0.4 | 1.8 | |||||||
Cediranib | 75.6 | 72.6 | 71.5 | 72.7 | 73.8 | 67.5 | 45.9 | 32.8 | 57.2 |
↵a Data with 1-ABT are not available.
↵b —, peaks for M1 and M5 could not be separated chromatographically; the value stated for M1 is the combined proportion of total chromatogram radioactivity for metabolites M1 and M5.
↵c ✓, component was present but did not account for greater than 1% of the chromatogram radioactivity.