PT  - JOURNAL ARTICLE
AU  - Xiaodong Lu
AU  - Cheng Li
AU  - David Fleisher
TI  - Cimetidine Sulfoxidation in Small Intestinal Microsomes
DP  - 1998 Sep 01
TA  - Drug Metabolism and Disposition
PG  - 940--942
VI  - 26
IP  - 9
4099  - http://dmd.aspetjournals.org/content/26/9/940.short
4100  - http://dmd.aspetjournals.org/content/26/9/940.full
SO  - Drug Metab Dispos1998 Sep 01; 26
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