Effects of quinidine and quinidine analogs on the formation of 5-hydroxydiclofenac in incubations with human liver microsomes or recombinant CYP3A41-a
| Modulator | 5-Hydroxydiclofenac | ||
|---|---|---|---|
| HLM Incubation1-b | CYP3A4 Incubation | ||
| μM | % control1-c | ||
| Quinidine | 20 | 420 | 420 |
| Quinidine | 100 | 620 | 490 |
| Quinine | 20 | 600 | N.D.1-d |
| Quinine | 100 | 900 | 700 |
| Epiquinidine | 20 | 360 | N.D. |
| Epiquinidine | 100 | 590 | 500 |
| Epiquinine | 20 | 400 | N.D. |
| Epiquinine | 100 | 580 | 400 |
| Hydroquinidine | 100 | 1100 | 790 |
| Hydroquinine | 100 | 1600 | 1350 |
| Cinchonidine | 100 | 700 | 600 |
| Cinchonine | 100 | 600 | 500 |
| 3-Hydroxyquinidine | 100 | 900 | 600 |
| Chloroquine | 100 | 100 | 50 |
| 7,8-Benzoflavone | 20 | 53 | 12 |
| 7,8-Benzoflavone | 100 | 45 | 9 |
↵1-a Diclofenac and glutathione in phosphate buffer (pH 7.4) and quinidine or its analogs in methanol were added to human liver microsomes or recombinant CYP3A4+OR+b5 suspended in phosphate buffer (0.1 M, pH 7.4) containing EDTA. Controls contained no quinidine but the same amount of methanol. Incubations were performed in duplicate.
↵1-b HLM, human liver microsomes.
↵1-c % Control was based on the formation of 5-hydroxydiclofenac in test incubations relative to the values in control experiments that lacked quinidine.
↵1-d N.D., not determined.