Enzyme kinetic parameters for ramelteon metabolism in recombinant human P450 enzymes
Values are mean (S.E.) of triplicate determinations.
| KM | Vmax | CLint | Percentage Contribution | |
|---|---|---|---|---|
| μM | pmol/(min × pmol P450) | μl/(min × pmol P450) | ||
| CYP1A2 | ||||
| Metabolite A | 60 (4) | 42 (1) | 0.69 | 22 |
| Metabolite B | 99 (5) | 11 (0) | 0.11 | 3.4 |
| Metabolite D | 64 (5) | 16 (0) | 0.26 | 8.1 |
| Metabolite E | 62 (4) | 53 (1) | 0.85 | 27 |
| Metabolite F | 49 (4) | 58 (2) | 1.2 | 38 |
| Metabolite G | N.D. | N.D. | 0.0026 | 0.08 |
| Metabolite H | 570 (90) | 17 (2) | 0.03 | 1.0 |
| CYP2C19 | ||||
| Metabolite A | 36 (6) | 0.58 (0.03) | 0.016 | 0.2 |
| Metabolite B | 26 (3) | 8.1 (0.2) | 0.31 | 3.6 |
| Metabolite D | 19 (2) | 1.1 (0) | 0.059 | 0.7 |
| Metabolite E | 18 (1) | 53 (1) | 3.0 | 34 |
| Metabolite F | 12 (1) | 60 (1) | 5.2 | 61 |
| Metabolite G | N.D. | N.D. | 0.0026 | 0.03 |
| Metabolite H | N.D. | N.D. | 0.022 | 0.3 |
| CYP3A4 | ||||
| Metabolite A | N.D. | N.D. | 0.0008 | 0.05 |
| Metabolite C | 150 (20) | 100 (10) | 0.71 | 42 |
| Metabolite D | 300 (20) | 13 (1) | 0.043 | 2.5 |
| Metabolite E | 280 (20) | 53 (4) | 0.19 | 11 |
| Metabolite F | 250 (20) | 50 (2) | 0.20 | 12 |
| Metabolite G | 80 (10) | 42 (2) | 0.52 | 31 |
| Metabolite H | N.D. | N.D. | 0.020 | 0.95 |
N.D., not determined.