PT  - JOURNAL ARTICLE
AU  - Chauret, Nathalie
AU  - Gauthier, Annick
AU  - Nicoll-Griffith, Deborah A.
TI  - Effect of Common Organic Solvents on <em>in Vitro</em>Cytochrome P450-Mediated Metabolic Activities in Human Liver Microsomes
DP  - 1998 Jan 01
TA  - Drug Metabolism and Disposition
PG  - 1--4
VI  - 26
IP  - 1
4099  - http://dmd.aspetjournals.org/content/26/1/1.short
4100  - http://dmd.aspetjournals.org/content/26/1/1.full
SO  - Drug Metab Dispos1998 Jan 01; 26
AB  - 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: phenacetinO-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 6β-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 ≤1%, except for P4502C8/9 and 2E1. Acetonitrile did not noticeably change the catalytic activity of the P4502C8/2C9, 2C19, 2D6, and 2E1 enzymes at concentrations ≤1%. It was found that the content level of the organic solvents should be kept lower than 1% because, for all three solvents, a concentration of 5% strongly affected the metabolism of the various probes. These findings should be taken into consideration when designing in vitrometabolism studies of new chemical entities. The American Society for Pharmacology and Experimental Therapeutics