Effect of several COX-2 inhibitors on the covalent binding of [14C]rofecoxib to aorta homogenate of rat and human (mean ± S.D., n = 3)
[14C]Rofecoxib (50 μM) was incubated with aortic homogenate [5% (w/v)] in the presence or absence of each of the COX-2 inhibitors (0.5 mM) at 37°C for 2 h. In a separate study, the homogenate was incubated with 25 μM [14C]rofecoxib (only for humans), 100 μM [14C]rofecoxib, or 50 μM [14C]celecoxib at 37°C for 2 h (n = 3). The amount of covalent binding was measured as described under Materials and Methods.
Substrate | Inhibitor | Covalent binding (μg Eq/g aorta) | ||
|---|---|---|---|---|
| Rat | Human | |||
| [14C]Rofecoxib (50 μM) | — | 1.66 ± 0.07 | 0.46 ± 0.02 | |
| Rofecoxib | 0.88 ± 0.47** | 0.10 ± 0.05*** | ||
| Celecoxib | 1.90 ± 0.15 | 0.50 ± 0.01 | ||
| Valdecoxib | 1.66 ± 0.11 | 0.53 ± 0.06 | ||
| Etoricoxib | 1.74 ± 0.17 | 0.49 ± 0.03 | ||
| CS-706 | 1.77 ± 0.06 | 0.51 ± 0.02 | ||
| [14C]Rofecoxib (25 μM) | — | N.D. | 0.24 ± 0.01*** | |
| [14C]Rofecoxib (100 μM) | — | 3.75 ± 0.12*** | 0.88 ± 0.05*** | |
| [14C]Celecoxib (50 μM) | — | 0.19 ± 0.17*** | 0.09 ± 0.09*** | |
—, control; N.D., no data.
↵** P < 0.01, ***P < 0.001, significantly different from the control by ANOVA followed by Dunnett's test.