CIMETIDINE SULFOXIDATION IN SMALL-INTESTINAL MICROSOMES

In previous studies, sulfoxide metabolite was observed in animal and h uman intestinal perfusions of cimetidine and other H-2-antagonists in vivo. L-Methionine, imipramine, and the anionic exchange inhibitor dii sothiocyanostilbene-2,2'-disulfonic acid reduced metabolite appearance . A sequence of follow-up studies is underway, for the purpose of asse ssing the contributions of drug metabolism and drug and metabolite tra nsport 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 wa s studied from three different species and two intestinal regions. Bas ed on preparation activity and tissue availability, the relative contr ibutions of flavin-containing monooxygenases and cytochrome P450 enzym es to cimetidine sulfoxidation were evaluated in rabbit jejunal micros omes. Additional inhibitor studies were carried out to evaluate the ro le of microsomal cimetidine sulfoxidation in the previous in vivo obse rvations.