Metabolism of etoricoxib in the presence of insect cell microsomes containing various cDNA-expressed P450 proteins
| CYP | pmol/h/pmol | pmol/h/mg3-a | % of Total Activity |
|---|---|---|---|
| CYP3A4 + b 5 | 20 | 2146 | 58 |
| CYP1A2 | 1.2 | 52 | 1.4 |
| CYP2A6 | 0.3 | 23 | 0.6 |
| CYP2E1 + b 5 | N.D. | N.D. | N.D. |
| CYP2C9*1 | 2.3 | 222 | 6.0 |
| CYP2C8 | 0.2 | 15 | 0.4 |
| CYP2D6 | 95.1 | 951 | 26 |
| CYP2C19 | 16 | 304 | 8.2 |
| Total3-b | 3712 | 100 |
N.D., no activity detected.
↵3-a Hydroxylation of etoricoxib (10 μM) in the presence of each P450 form (pmol/h/pmol of CYP) was normalized with respect to the nominal level of each P450 form present in native human liver microsomes (data supplied by GENTEST Corp.): CYP1A2, 45 pmol/mg; CYP2C19, 19 pmol/mg; CYP3A4 (CYP3A5 assumed absent), 108 pmol/mg; CYP2D6, 10 pmol/mg; CYP2E1, 49 pmol/mg; CYP2A6, 68 pmol/mg; CYP2C9, 96 pmol/mg; and CYP2C8, 64 pmol/mg. Normalized rates are expressed as pmol/h/mg of microsomal protein. All insect cell microsome preparations contained overexpressed NADPH P450 reductase. However, CYP3A4 and CYP2E1 were also co-expressed with cytochromeb 5.
↵3-b Sum of normalized rates.