Tramadol metabolism to tramadol metabolites M1, M2, M3, and M5 in human liver microsomes
| Microsomal Preparation | Tramadol Substrate Concentration | Tramadol Metabolism (pmol/min/mg protein)2-a | ||||
|---|---|---|---|---|---|---|
| M1 | M2 | M3 | M5 | Total2-b | ||
| μM | ||||||
| Pool I | 20 | 22.1 (38.3)2-c | 33.2 (57.5) | 0.7 (1.2) | 1.7 (3.0) | 57.7 (100) |
| Pool I | 200 | 93.0 (24.4) | 278.3 (73.0) | 5.0 (1.3) | 4.9 (1.3) | 381.2 (100) |
| Pool I | 500 | 148.0 (28.5) | 367.0 (70.8) | 3.3 (0.6) | 0.3 (0.1) | 518.6 (100) |
| Pool II | 500 | 87.3 (40.3) | 128.7 (59.4) | <0.1 (0) | 0.7 (0.3) | 216.7 (100) |
↵2-a Duplicate test and single blank incubations were performed with each tramadol substrate concentration and each human liver microsomal preparation. Incubations were performed with 0.4 to 1.0 mg of microsomal protein for 5 or 10 min.
↵2-b Sum of tramadol metabolism to metabolites M1, M2, M3, and M5.
↵2-c Numbers in parentheses are percentages of total tramadol metabolism.