RT Journal Article SR Electronic T1 Cimetidine Sulfoxidation in Small Intestinal Microsomes JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 940 OP 942 VO 26 IS 9 A1 Xiaodong Lu A1 Cheng Li A1 David Fleisher YR 1998 UL http://dmd.aspetjournals.org/content/26/9/940.abstract AB In previous studies, sulfoxide metabolite was observed in animal and human intestinal perfusions of cimetidine and other H2-antagonists in vivo. L-Methionine, imipramine, and the anionic exchange inhibitor diisothiocyanostilbene-2,2′-disulfonic acid reduced metabolite appearance. A sequence of follow-up studies is underway, for the purpose of assessing the contributions of drug metabolism and drug and metabolite transport to variable drug absorption. In this regard, drug-drug and drug-nutrient interactions represent a primary focus of this research. The S-oxidation of cimetidine in mammalian small intestinal microsomes was studied from three different species and two intestinal regions. Based on preparation activity and tissue availability, the relative contributions of flavin-containing monooxygenases and cytochrome P450 enzymes to cimetidine sulfoxidation were evaluated in rabbit jejunal microsomes. Additional inhibitor studies were carried out to evaluate the role of microsomal cimetidine sulfoxidation in the previous in vivo observations. The American Society for Pharmacology and Experimental Therapeutics