Summary of the metabolite profiles of compounds 1 and 2 obtained from incubations with liver S9 (human, rat), hepatocytes (human, rat), and bile (BDC rats)
The relative abundances (percentages) of the drug-related materials in incubations or matrices were estimated based on the UV peak areas (λ = 303 nm) assuming absorption coefficients of the parent compounds and their metabolites were similar. Metabolite names 1-1, 1-2, 2-1, and 2-2 are given in parentheses.
| Compound and Matrix | Parent | Metabolism on the Bicyclo[1.1.1]Pentane Moiety | Metabolism on Other Moieties | |||
|---|---|---|---|---|---|---|
| Mono-Oxidation | P + 181 Da | Bis-Oxidation | Mono-/Bis-Oxidation + Dehydrogenation | Mono-Oxidation, etc. | ||
| Compound 1 | ||||||
| AIRLS9 (30 min) | 98 | 2 (1-1) | ND | ND | ND | ND |
| HLS9 (30 min) | 99 | <1 (1-1, 1-2) | ND | ND | ND | ND |
| RHep (2 h) | 99 | <1 (1-1) | ND | ND | ND | ND |
| HHep (2 h) | 99 | <1 (1-1) | ND | ND | ND | ND |
| BDC rat bile (0–24 h) | 1 | 27 (1-1), 1 (1-2) | 52 (1-3) | 3 (2 products) | 13 (4 products) | 4 |
| BDC rat plasma (0.5, 1, 3, 6, 24 h) | 76‒95 | 4–16 (1-1), 2–11 (1-2) | ND | ND | ND | ND |
| Compound 2 | ||||||
| AIRLS9 (30 min) | 95 | 5 (2-1) | ND | ND | ND | ND |
| HLS9 (30 min) | 99 | <1 (2-1) | ND | ND | ND | ND |
| RHep (2 h) | 99 | <1 (2-1) | ND | ND | ND | ND |
| HHep (2 h) | 99 | <1 (2-1) | ND | ND | ND | ND |
| BDC rat bile (0–24 h) | 4 | 55 (2-1), 6 (2-2) | 6 (2-3) | 4 (1 product) | 18 (4 products) | 13 |
| BDC rat plasma (0.5, 1, 3, 6, 24 h) | 100 | ND | ND | ND | ND | ND |
AIRLS9, Aroclor-induced rat liver S9; HHep, human hepatocyte; HLS9, human liver S9; ND, not detected; RHep, rat hepatocyte.