RT Journal Article SR Electronic T1 Epoxide Hydrolase-Dependent Metabolism of Butadiene Monoxide to 3-Butene-1,2-diol in Mouse, Rat, and Human Liver JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 1013 OP 1015 VO 25 IS 8 A1 Renee J. Krause A1 Jane E. Sharer A1 Adnan A. Elfarra YR 1997 UL http://dmd.aspetjournals.org/content/25/8/1013.abstract AB Incubations of butadiene monoxide (BMO) with mouse, rat, and human liver microsomes or cDNA-expressed human microsomal epoxide hydrolase led to 3-buten-1,2-diol (BDD) detection; the BDD peak exhibited a GC/MS fragmentation pattern similar to that of reference material. Incubations with rat liver cytosol did not lead to BDD detection; however, when mouse or human liver cytosol was used, BDD was detected but at levels lower than those detected with the liver microsomes. The catalytic efficiency (Vmax/Km ratio) of BDD formation in rat liver microsomes was nearly 3-fold higher than the ratio obtained with mouse liver microsomes. Among two human liver microsomal samples, one sample exhibited a ratio that was nearly 3-fold higher than that of rat liver microsomes, and the second sample exhibited a ratio that was similar to that of rat liver microsomes. Although these results suggest epoxide hydrolases may play a role in BMO metabolism in vivo, rats and mice given BMO (71.3–285 μmol/kg) excreted <1% of the dose as BDD into urine within 24 hr. Thus, further studies into the role of epoxide hydrolases in BMO metabolism and disposition and the fate of BDD are warranted. The American Society for Pharmacology and Experimental Therapeutics