Table 2.
Contribution (fm expressed in percentage) of CYPs (based on 1-aminobenzotriazole inhibitory effect), CYP3A4 (based on ketoconazole inhibitory effect) and MAO (based on clorgyline inhibitory effect) to the individual metabolic clearance of dronedarone and its metabolites in each of the four different cryopreserved human hepatocyte preparations
| fm | BD-91 | BD-296 | HU-1358 | IVT-IBG | Mean ± SD |
|---|---|---|---|---|---|
| Dronedarone | |||||
| Total CYPs (%) | 98 | 99 | 98 | 95 | 98 ± 2 |
| CYP3A4 (%) | 95 | 95 | 84 | 80 | 89 ± 7 |
| MAO (%) | 18 | – | 23 | 43 | 29 ± 14 |
| N-debutyl-dronedarone | |||||
| Total CYPs (%) | 67 | 48 | 51 | 54 | 55 ± 7 |
| CYP3A4 (%) | 7 | 4 | 8 | 0 | 5 ± 3 |
| MAO (%) | 88 | 80 | 86 | 83 | 84 ± 3 |
| Propanoic acid-dronedarone | |||||
| Total CYPs (%) | 87 | 92 | 91 | 89 | 90 ± 3 |
| CYP3A4 (%) | 36 | 41 | 33 | 34 | 36 ± 3 |
| MAO (%) | 12 | 0 | 0 | 0 | 3 ± 5 |