Effect of dietary factors and environmental chemicals on intestinal drug metabolizing enzymes

Abstract

The liver is the major site of metabolism of foreign chemicals, but contribution from intestinal biotransformation can influence the overall disposition of chemicals. The intestinal drug‐metabolizing enzymes are located in the endoplasmic reticulum and they possess biochemical properties similar to those of the hepatic system. In general, the rate of in vitro metabolism of drug substrates in intestines is lower than in the liver. There seem to be differences in regulation and induction of hepatic and intestinal drug‐metabolizing enzymes. The in vitro intestinal metabolism of foreign chemicals is affected by several factors including the nutritional status of the animal. Dietary components such as vitamins, lipids and vegetables can modify the activities of intestinal drug‐metabolizing enzymes. Phenobarbital or 3‐methyl‐cholanthrene (3‐MC) pre‐treatment induces the hepatic metabolism of a wide variety of drug substrates in a number of species, while the stimulation of intestinal enzymes is both substrate and species specific. Rabbit intestinal drug‐metabolizing enzymes seem to be resistant to induction by foreign chemicals.