Dietary effects on drug metabolism and transport.

Metabolic food-drug interactions occur when the consumption of a particular food modulates the activity of a drug-metabolising enzyme system, resulting in an alteration of the pharmacokinetics of drugs metabolised by that system. A number of these interactions have been reported. Foods that contain complex mixtures of phytochemicals, such as fruits, vegetables, herbs, spices and teas, have the greatest potential to induce or inhibit the activity of drug-metabolising enzymes, although dietary macroconstituents (i.e. total protein, fat and carbohydrate ratios, and total energy intake) can also have effects. Particularly large interactions may result from the consumption of herbal dietary supplements. Cytochrome P450 (CYP) 3A4 appears to be especially sensitive to dietary effects, as demonstrated by reports of potentially clinically important interactions involving orally administered drugs that are substrates of this enzyme. For example, interactions of grapefruit juice with cyclosporin and felodipine, St John's wort with cyclosporin and indinavir, and red wine with cyclosporin, have the potential to require dosage adjustment to maintain drug concentrations within their therapeutic windows. The susceptibility of CYP3A4 to modulation by food constituents may be related to its high level of expression in the intestine, as well as its broad substrate specificity. Reported ethnic differences in the activity of this enzyme may be partly due to dietary factors. Food-drug interactions involving CYP1A2, CYP2E1, glucuronosyltransferases and glutathione S-transferases have also been documented, although most of these interactions are modest in magnitude and clinically relevant only for drugs that have a narrow therapeutic range. Recently, interactions involving drug transporters, including P-glycoprotein and the organic anion transporting polypeptide, have also been identified. Further research is needed to determine the scope, magnitude and clinical importance of food effects on drug metabolism and transport.