Success of the micropatterned hepatocyte coculture system at generation of major human metabolites for 27 compounds compared to other in vitro systemsa
| In Vivo | Microsomesb | S-9b | Hepatocyte Suspensionb | Micropatterned Coculture | ||
|---|---|---|---|---|---|---|
| 48 h | 7 Days | |||||
| Excretory metabolites >10% of dose | ||||||
| All excretory metabolites | 39 | 19 (49) | 22 (56) | 25 (64) | 27 (69) | 32 (82) |
| Metabolites arising by phase 1 reactions only | 29 | 17 (59) | 19 (66) | 19 (66) | 20 (69) | 24 (83) |
| Metabolites arising by a phase 2 reaction | 10 | 2 (30) | 3 (30) | 6 (60) | 7 (70) | 8 (80) |
| Metabolites that are one reaction from parent (primary) | 16 | 12 (69) | 11 (69) | 12 (75) | 13 (81) | 15 (94) |
| Metabolites that are two or more reactions from parent (secondary) | 23 | 7 (48) | 11 (48) | 13 (57) | 14 (61) | 17 (74) |
| Circulatory metabolites >10% of total drug-related material | ||||||
| All circulating metabolites | 40 | 17 (43) | 19 (48) | 21 (53) | 28 (70) | 30 (75) |
| Metabolites arising by phase 1 reactions only | 31 | 14 (52) | 16 (52) | 14 (45) | 22 (71) | 23 (74) |
| Metabolites arising by a phase 2 reaction | 9 | 3 (33) | 3 (33) | 7 (78) | 6 (67) | 7 (78) |
| Metabolites that are one reaction from parent (primary) | 16 | 11 (69) | 11 (69) | 12 (75) | 12 (75) | 14 (88) |
| Metabolites that are two or more reactions from parent (secondary) | 24 | 6 (25) | 8 (33) | 9 (38) | 16 (67) | 16 (67) |