Cimetidine sulfoxidation in small intestinal microsomes.

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.