Effect of CYP2C8 substrates and inhibitors on the metabolism of tazarotenic acid to the sulfoxide metabolite
| Inhibitor | IC50± S.E. | Ki ± S.E. | i1-a |
|---|---|---|---|
| μM | |||
| Paclitaxel (Taxol) | 14.9 ± 6.2 | 30.0 ± 7.0 | 0.00743–0.123 |
| 9-cis-Retinoic acid (Panretin) | 17.6 ± 2.8 | 20.2 ± 8.7 | 0.00483–0.0242 |
| 13-cis-Retinoic acid (Accutane) | 15.1 ± 2.5 | 66.2 ± 14.3 | 0.0178–0.0474 |
| Quercetin | 4.07 ± 2.69 | 19.7 ± 8.2 | 0.00108–0.0207 |
↵1-a i = Predicted fractional inhibition in vivo based on anticipated human plasma concentration following oral administration of tazarotenic acid (0.6 μM), paclitaxel (Taxol) (0.23–4.3 μM) (PDR entry), 13-cis-retinoic acid (Accutane) (0.556–1.53 μM) (PDR entry), 9-cis-retinoic acid (0.149–0.762 μM) (Rizvi et al., 1998), quercetin (0.00331–0.648 μM) (Hollman et al., 1996), and a Km value of 25 μM under these tazarotenic acid incubation conditions.