Inhibition of daphnetin glucuronidation in HLM, HIM, and recombinant UGTs with mefenamic acid and phenylbutazone
Daphnetin was incubated with microsomes (0.1 mg/ml) and UDPGA (5 mM) for 10 min in the presence of mefenamic acid (1–50 μM) or phenylbutazone (10–500 μM). The IC50 values are given as mean ± computer-calculated S.E. of the estimate.
| UGT Source | IC50 | |||
|---|---|---|---|---|
| Mefenamic Acid | Phenylbutazone | |||
| M-1 | M-2 | M-1 | M-2 | |
| μM | ||||
| UGT1A6 | >50 | >50 | 41.1 ± 5.6 | 40.3 ± 4.2 |
| UGT1A9 | 8.1 ± 1.6 | 2.5 ± 0.2 | 36.4 ± 2.8 | 39.2 ± 3.2 |
| HLM | 10.4 ± 2.2 | 10.5 ± 2.6 | 52.3 ± 4.1 | 59.4 ± 3.4 |
| HIM | 8.8 ± 0.9 | 7.8 ± 2.7 | 57.2 ± 3.6 | 61.2 ± 2.4 |