Table 2.
Summary of inhibitory potencies for thromboxane B2 (TxB2) and prostaglandin E2 (PGE2) production in the human whole blood assay
| Treatment (donors) | TxB2 (COX-1) | PGE2 (COX-2) | COX-2 selectivity |
|---|---|---|---|
| IC50 (μM) | IC50 (μM) | ||
| Nonselective COX inhibitors | |||
| Diclofenac (52) | 0.097 (±0.001) | 0.013 (±0.0001) | 7 |
| Ibuprofen (10) | 17 (±5) | 9 (±0.3) | 2 |
| Naproxen (15) | 10 (±0.3) | 21 (±0.7) | 0.5 |
| Selective COX-2 inhibitors | |||
| Celecoxib (14) | 7 (±0.3) | 0.19 (±0.1) | 37 |
| Etodolac (11) | 42 (±3) | 0.95 (±0.09) | 45 |
| Etoricoxib (14) | 69 (±5) | 0.26 (±0.02) | 265 |
| Lumiracoxib (52) | 67 (±2) | 0.13 (±0.002) | 515 |
| Meloxicam (14) | 3 (±0.1) | 0.11 (±0.004) | 26 |
| Nimesulide (7) | 35 (±3) | 0.69 (±0.05) | 51 |
| Rofecoxib (14) | 24 (±0.5) | 0.17 (±0.01) | 141 |
| Valdecoxib (16) | 27 (±2) | 0.1 (±0.005) | 270 |
| Metabolite of lumiracoxib | |||
| 4′-hydroxy lumiracoxib (11) | 86 (±9) | 0.5 (±0.01) | 172 |
Inhibition of TxB2 and PGE2 production was determined in separate aliquots of blood that had been pretreated with compounds for 1 h. TxB2 production was stimulated with the addition of A23187 (50 μM) and assessed after 1 h incubation. PGE2 production was induced with LPS (10 μg ml−1) and assessed after overnight incubation. Prostanoid production was normalised to percent inhibition and the results from the donors pooled. The IC50 indicated here is the mean value for the number of donors indicated in parentheses, along with the s.e.mean. The COX-2 selectivity represents the ratio of IC50 for COX-1 divided by COX-2.