Effect of common organic solvents on in vitro cytochrome P450-mediated metabolic activities in human liver microsomes.

In this study, we report the effect of methanol, dimethyl sulfoxide (DMSO), and acetonitrile on the cytochrome P450 (P450)-mediated metabolism of several substrates in human liver microsomes: phenacetin O-deethylation for P4501A2, coumarin 7-hydroxylation for P4502A6, tolbutamide hydroxylation for P4502C8/2C9, S-mephenytoin 4'-hydroxylation for P4502C19, dextromethorphan O-demethylation for P4502D6, chlorzoxazone 6-hydroxylation for P4502E1, and testosterone 6beta-hydroxylation for P4503A4. DMSO was found to inhibit several P450-mediated reactions (2C8/2C9, 2C19, 2E1, and 3A4) even at low concentrations (0.2%). There was no measurable effect on the catalytic activity of the various P450s when methanol was present at levels