Influences of diet and nutrition on clinical pharmacokinetics

The human diet represents a complex and variable mixture of nutrients, many of which have the potential for altering the disposition of drugs. This review highlights progress from a number of laboratories illustrating nutrient influences on drug dispositions and actions. Emphasis is placed on nutritional effects on hepatic drug metabolism studied in humans. Data from animals have sometimes been difficult to extrapolate to humans, as illustrated by reports on the influences of starvation, dietary lipids, and ascorbic acid. From studies in healthy subjects it is now clear that a number of specific dietary factors can influence drug metabolism by the mixed function oxidase system and conjugating enzymes. These include dietary protein, cruciferous vegetables, charcoal-broiled beef containing polycyclic aromatic hydrocarbons, and methylxanthines. The effects of such dietary components have been demonstrated for only a limited number of drug substrates for these enzyme systems. Effects of food on bioavailability have been more widely studied, and depend greatly upon the type of drug. Malnutrition can be associated with variable but potentially important effects on the bioavailability, binding, hepatic metabolism, and renal clearance of drugs. In malnourished patients it is generally difficult to recognise the roles of individual nutrient deficiencies on drug disposition, and clinical predictors of altered pharmacokinetics for various drugs in such patients are not well defined. It is likely that many important interrelationships between nutrition and new or already marketed drugs remain to be recognised, and therefore warrant further research. Nutritional effects on drug metabolising enzymes also have implications for endogenous substances such as hormones and environmental toxins and carcinogens which are metabolised by the same or related enzyme systems, and for diseases likely to be related to the actions of such chemicals.