Chapter 21 - Fate of drug-metabolizing enzymes in malnutrition: Challenges and strategies

Abstract

Drug metabolism is affected by the nutritional status of individuals. The changes in the activities of drug-metabolizing enzymes (DMEs) due to malnutrition have been observed in various studies. Drug metabolism and diposition usually involve oxidation, protein-binding alterations, and conjugation reactions. Protein calorie malnutrition results in altered drug metabolism in humans as well as laboratory animals. Similarly, metabolism of various drugs was observed to be depressed by fat-free diet in experimental animals. Induction of cytochrome P450 enzymes and drug-hydroxylation were observed to be reduced in experimental animals due to fat-free diet. The activity of hepatic DMEs is depressed in rats on calcium, zinc, and magnesium-free diet. Most of the data ascertaining the relationship between nutritional status and DMEs are primarily extracted from animal studies, and investigations on malnourished human subjects are scarce. Considering the substantial impact of nutritional status on the activities of DMEs, controlled human studies are the need of hour and must be conducted to validate the findings from animal models.