Table 3

Metabolism of etoricoxib in the presence of insect cell microsomes containing various cDNA-expressed P450 proteins

CYPpmol/h/pmolpmol/h/mg3-a % of Total Activity
CYP3A4 + b 5 20214658
CYP2E1 + b 5 N.D.N.D.N.D.
Total3-b 3712100
  • 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.