Table 2. Metabolism of Authentic Metabolites of 1 upon Incubation with Hepatic Microsomes at a Substrate Concentration of 1 μM and Microsomal Protein Concentration of 0.4 mg/mLa.
| CLint (μL/(min mg)) |
|||
|---|---|---|---|
| metabolite incubated | human | rhesus monkey | rat |
| M-14 (I) O-demethylation (2) | <3 | 8.0 | 264 |
| M-14 (II) O-demethylation (6) | highly unstable in all species | ||
| M-28 N-deethylation (3) | <3 | 19 | 24 |
| M-42 O-demethylation + N-deethylation (4) | <3 | 12 | 45 |
| M-56 (II) N,N-dideethylation (5) | 6.0 | 7.3 | 4.4 |
a
Incubations were conducted in the presence of NADPH at 37 °C over a 60 min period. Data represent a single incubation only.