Semi-quantitative prediction of in vivo metabolism of compound A, B, and C by various in vitro systems
| Metabolite | In vivo4-d | In vitro/in vivo4-e | |||
|---|---|---|---|---|---|
| Hepatocytes | Liver Slices (Fresh) | Liver Slice (Cryo) | All Organ Slices | ||
| Compound A4-a | urine | ||||
| 1 | 82.4 | 1.2 | 1.1 | 1.2 | 1.2 |
| 2 | 17.6 | 0.23 | 0.4 | 0.3 | 0.10 |
| Compound B4-b | bile +urine | ||||
| 1 | 3.2 | 2.6 | 2.6 | 0.8 | —4-f |
| 2 | 8 | 0.9 | 0.7 | 0.6 | |
| 3 | 15 | 1.2 | 0.6 | 0.42 | |
| 4 | 3 | 3.1 | 3.6 | 3.0 | |
| 5 | 1.5 | 7 | 2.0 | 2.5 | |
| 6 | 19.5 | 0.8 | 0.7 | 0.9 | |
| 7 | 2.5 | 2.1 | 0.6 | 0 | |
| 8 | 47 | 0.5 | 1.0 | 1.2 | |
| Compound C4-c | bile | ||||
| 1 | 87.1 | 0.06 | 0.18 | 0.15 | 0.75 |
| 2 | 0.7 | 0 | 0 | 0 | 0 |
| 4 | 12.1 | 4.75 | 4.17 | 3.29 | 1.72 |
Bold indicates “important” metabolites.
↵4-a For the metabolic route see Fig. 1.
↵4-b For the metabolic route see Fig. 3.
↵4-c For the metabolic route see Fig. 5.
↵4-d % of the total amount of metabolites in vivo.
↵4-e Ratio of the % of the total amounts of metabolites predicted in vitro and the % of the total amounts of metabolites actually formed in vivo.
↵4-f Extra-hepatic metabolism was insignificant.