Table 4

Correlation coefficients (r) for comparing the formation of various E1 metabolites with the activities of CYP1A2, 2B6, 3A4, or 3A4/5 by measuring the metabolism of probe substrates in 33 human liver microsomes (21 male and 12 female)

E1 Metabolite FormedTotal P450 ContentCYP1A2 (CaffeineN3-Demethylation)CYP2B6 (S-MephenytoinN-Demethylation)CYP3A4 (DextromethorphanN-Demethylation)CYP3A4/5 (Testosterone 6β-Hydroxylation)
MaleFemaleTotalMaleFemaleTotalMaleFemaleTotalMaleFemaleTotalMaleFemaleTotal
y-OH-E2 0.55* 0.88*** 0.74*** 0.250.380.270.60** 0.81** 0.72*** 0.56* 0.69* 0.66*** 0.80*** 0.96 *** 0.91 ***
y-OH-E1 0.61** 0.88*** 0.75*** 0.250.490.310.59** 0.94 *** 0.77*** 0.66** 0.84*** 0.79*** 0.89*** 0.95 *** 0.93 ***
6β-OH-E1 0.60** 0.83*** 0.72*** 0.270.400.260.59** 0.88*** 0.74*** 0.58** 0.81** 0.74*** 0.78*** 0.90 *** 0.87***
16α-OH-E1 +16β-OH-E1 0.63** 0.82** 0.73*** 0.46* 0.63* 0.47** 0.80*** 0.95 *** 0.86*** 0.81*** 0.89*** 0.86*** 0.78*** 0.87*** 0.86***
6-keto-E1 +M20.64** 0.86*** 0.75*** 0.57** 0.76** 0.69*** 0.54* 0.94 *** 0.77*** 0.71*** 0.92 *** 0.81*** 0.74*** 0.83*** 0.73***
4-OH-E2 0.73*** 0.92 *** 0.82*** 0.61** 0.66* 0.60*** 0.70*** 0.95 *** 0.83*** 0.65** 0.89*** 0.77*** 0.77*** 0.91 *** 0.80***
2-OH-E2 0.71*** 0.90 *** 0.78*** 0.370.70* 0.54** 0.47* 0.94 *** 0.69*** 0.410.86*** 0.60*** 0.80*** 0.88*** 0.74***
2-OH-E1 0.77*** 0.82** 0.80*** 0.55* 0.78** 0.67*** 0.59** 0.97 *** 0.80*** 0.53* 0.91 *** 0.74*** 0.81*** 0.80** 0.76***
4-OH-E1 0.62** 0.82** 0.73*** 0.320.64* 0.46** 0.51* 0.96 *** 0.77*** 0.50* 0.89*** 0.76*** 0.87*** 0.82** 0.84***
E2 −0.070.03−0.05−0.23−0.29−0.18−0.05−0.35−0.21−0.28−0.38−0.37−0.02−0.01−0.11
X0.61** 0.90 *** 0.75*** 0.230.460.260.63** 0.90 *** 0.75*** 0.62** 0.80** 0.74*** 0.89*** 0.96 *** 0.93 ***
Total E1metabolized0.70*** 0.92 *** 0.82*** 0.360.60* 0.45** 0.64** 0.94 *** 0.81*** 0.59** 0.86*** 0.76*** 0.89*** 0.94 *** 0.91 ***

Note. Microsomal formation of various estrogen metabolites was as described in the legend to Table 3. The CYP1A2, 2B6, 3A4, or 3A4/5 activities in human liver microsomes were determined by the supplier by measuring the activity for caffeine N3-demethylation,S-mephenytoin N-demethylation, dextromethorphanN-demethylation, or testosterone 6β-hydroxylation, respectively, according to the published methods (Pearce et al. 1996). Exceptionally high correlation coefficients (r ≥ 0.9) are shown in bold. *P < 0.05; **P < 0.01; ***P < 0.001.