Inhibition of NPC formation by various inhibitors of CYPs
| CYP | Inhibitor (Concentration) | Solvent | NPC Formation |
|---|---|---|---|
| % of control | |||
| Nonselective | Cimetidine (100 μM) | Ethanol | 58.8 ± 9.6 |
| 1A2 | α-Naphthoflavone (1 μM) | Ethanol | 81.3 |
| 2A6 | Coumarin (100 μM) | Ethanol | 92.8 ± 8.2 |
| 2C8/9 | Sulfaphenazole (1 μM) | Ethanol | 92.8 ± 0.7 |
| 2D6 | Quinidine (5 μM) | Buffer | 75.4 ± 9.3 |
| 2E1 | Chlorzoxazone (100 μM) | Ethanol | 77.2 ± 12.2 |
| 3A | Ketoconazole (1 μM) | Ethanol | 1.4 ± 1.1 |
| 3A | Troleandomycin (100 μM) | Methanol | ND1-a |
Inhibition of NPC formation using pooled microsomes was estimated with 25 μM CPT-11 in the presence of selective inhibitors of CYP isoforms (Halpert et al., 1994). The rates of formation of NPC (estimated in three independent experiments) are expressed as percentages of those observed in corresponding control incubations containing equal amounts of drug solvent and are means ± SD.
↵1-a ND, no formation detected.