TABLE 3

Correlation (r) values between formation rates of MPA metabolites (M-2, M-3, and M-4) and P450 isoform-specific activities

MPA (10 μM) was incubated with liver microsomes (0.3 mg/ml) for 10 min.


P450s

P450 Isoform-Specific Reactions

M-2

M-3

M-4
CYP1Aa Phenacetin O-deethylation 0.62 0.61 0.61
CYP2A6a Coumarin 7-hydroxylation 0.82 0.82 0.83
CYP2C8a Paclitaxel 6α-hydroxylation 0.82 0.83 0.83
CYP2C9 Diclofenac 4′-hydroxylation −0.11 −0.11 −0.08
CYP2C19 S-Mephenytoin 4′-hydroxylation 0.14 0.14 0.13
CYP2D6 Dextromethorphan O-demethylation 0.31 0.32 0.35
CYP2E1 Chlorzoxazone 6-hydroxylation 0.37 0.39 0.42
CYP3A4 Testosterone 6β-hydroxylation 0.97 0.98 0.98
CYP3A4
Paclitaxel 3′-p-hydroxylation
0.99
0.99
0.98
  • a No metabolite formation was observed by recombinant CYP1A2, CYP2A6, and CYP2C8.