Effect of cimetidine on intestinal absorption & digestive functions in mice.

Oral administration of cimetidine, an antiulcerogenic drug, at a dose of 100 mg per kg body weight in mice, caused significant inhibition of glucose and amino acid uptake in small intestinal segments either after 2 and 24 h (single treatment) or 15 days (daily). Cimetidine also caused a significant decrease in intestinal brush border membrane associated enzymes, sucrase, lactase, maltase and alkaline phosphatase, but increases the activity of leucine aminopeptidase. Kinetic analysis indicated that cimetidine decreased the maximum of apparent initial enzyme velocity (Vmax) of disaccharidases, while substrate affinity constant (Km) was not altered, indicating the noncompetitive nature of inhibition. However, the inhibition of alkaline phosphatase was found to be of mixed type as both Km and Vmax were altered. In vitro addition of cimetidine also produced significant inhibition of enzymes, the inhibition constant (Ki) for sucrase, lactase, maltase and alkaline phosphatase being 22.8, 4.5, 11.5 and 4.8 mM, respectively. It was further observed that in vitro addition of cimetidine also decreased Vmax in case of maltase, sucrase and lactase, Km was unchanged, whereas in case of alkaline phosphatase there was a decrease in Vmax and increase in Km, as compared to the controls.