TABLE 3

Correlation analysis (r) of the relationship between the rates of metronidazole conversion to 2-hydroxymetronidazole with the sample-to-sample variation in cytochrome P450 activity in human liver microsomes

Values in bold indicate significant correlations between P450 activity and 2-hydroxymetronidazole formation at P < 0.05. Coumarin 7-hydroxlation was significantly correlated (r, P value) with S-mephenytoin N-hydroxylation (0.703, 0.001) and bupropion hydroxylation (0.576, 0.018).

	2-Hydroxymetronidazole Formation
Enzymatic Reaction (Enzyme)	100-μM Metronidazole ^{^a}		300-μM Metronidazole ^{^a}
Enzymatic Reaction (Enzyme)	r	P	r	P
7-Ethoxyresorufin O-deethylation (CYP1A2)	0.032	0.906	0.068	0.801
Phenacetin O-deethylation (CYP1A2)	0.107	0.692	0.128	0.635
Coumarin 7-hydroxylation (CYP2A6)	0.970	9.19 × 10⁻¹¹	0.972	5.17 × 10⁻¹¹
S-Mephenytoin N-hydroxylation (CYP2B6)	0.742	0.001	0.703	0.002
Bupropion hydroxylation (CYP2B6)	0.648	0.006	0.618	0.010
Paclitaxel 6α-hydroxylation (CYP2C8)	0.421	0.102	0.395	0.127
Diclofenac 4′-hydroxylation (CYP2C9)	0.181	0.502	0.165	0.540
S-Mephenytoin 4′-hydroxylation (CYP2C19)	0.419	0.010	0.375	0.149
Dextromethorphan O-demethylation (CYP2D6)	−0.072	0.791	−0.112	0.679
Chlorzoxazone 6-hydroxylation (CYP2E1)	−0.106	0.695	−0.102	0.706
Testosterone 6β-hydroxylation (CYP3A4/5)	0.282	0.288	0.221	0.410
Midazolam 1′-hydroxylation (CYP3A4/5)	0.298	0.260	0.245	0.359
Lauric acid 12-hydroxylation (CYP4A9/11)	−0.218	0.415	−0.214	0.424

r, Correlation coefficient.
↵^a Concentration of metronidazole present in microsomal incubations.