Effects of inhibitors of CYP1A2, 2C19 and 3A on ramelteon metabolism in pooled human liver microsomes
For metabolite formation, inhibition values are the mean of three determinations. For ramelteon consumption, measurements were duplicates. Ramelteon concentration was 10 μM when measuring metabolite formation and 1 μM when measuring ramelteon consumption.
| Inhibitor (Concentration) | Metabolite (Percentage Inhibition) | Ramelteon Consumption | ||||||
|---|---|---|---|---|---|---|---|---|
| A | B | C | D | E | F | G | ||
| Furafylline (20 μM) | 93 | 38 | <5 | 78 | 52 | 53 | <5 | 71 |
| N-Benzylnirvanol (20 μM) | 5 | <5 | <5 | 14 | <5 | 25 | 42 | 20 |
| Ketoconazole (3 μM) | <5 | 36 | 100 | 14 | <5 | 13 | 100 | 42 |
| Fluconazole (80 μM) | <5 | 37 | 89 | 17 | 17 | 33 | 93 | 23 |
| Fluconazole (30 μM) | <5 | 30 | 75 | <5 | <5 | 5 | 78 | 22 |