Influence of dietary components on the gastrointestinal metabolism and transport of drugs

There is widespread recognition that the ingestion of a meal is associated with a number of physiologic changes (gastric pH, gastric emptying, hepatic blood flow, etc.) that can significantly alter the rate and extent of drug absorption. It is also well recognized that the components of food can alter drug absorption through alterations in drug solubility. The nutritional status of a patient can also contribute to variability in the pharmacokinetics of certain drugs. The more recent finding that grapefruit juice can increase the bioavailability of certain drugs, by reducing presystemic intestinal metabolism, has led to renewed interest in the area of 'food-drug interactions.' Particular interest has focused on the effects of the grapefruit flavonoid, naringin, and the furanocoumarin, 6',7'-dihydroxybergamottin, on the activity of intestinal CYP3A4. The possibility that grapefruit juice might affect drug absorption via an interaction with intestinal P-glycoprotein (P-gp) is also being explored. The growing use of herbal extracts and phytopharmaceuticals raises a new challenge-will the use of these products cause changes in the pharmacokinetics of 'conventional' drugs? As a case in point, consider the phytoestrogenic isoflavones, which are being promoted for a number of health benefits. Isoflavones such as genistein and daidzein can inhibit oxidative and conjugative metabolism in vitro and interact with transporters such as P-gp and the canalicular multispecific organic anion transporter. Given that P-gp and canalicular multispecific organic anion transporter are involved in the intestinal absorption and biliary excretion of a wide range of drugs and metabolites, it is reasonable to suspect that isoflavones may alter drug disposition in humans. However, this possibility has not been explored.