Impact of physiological factors on drug-metabolizing enzymes: From function to regulation

Homo sapiens have complex biotransformation systems evolved for the detoxification of xenobiotics. The most common xenobiotics to which human beings are exposed from fetal life onward include drugs. Drug-metabolizing enzymes (DMEs) mainly responsible for detoxification consist of cytochromes responsible for wide metabolic activities and are found in every tissue of the body. Liver and gut are the main sites having highest concentration of biotransforming enzymes. Physiological and environmental factors affect the extent to which a particular drug will be biotransformed by a particular pathway. Physiological factors mainly depend on species, genetics, age, gender, and hormones of the individual. Drug-metabolizing pathways are mainly divided into two phases evolved differently in human beings. Development of phase 1 metabolic pathways start during gestation and may change during different phases of life, whereas phase 2 pathways develop perinatally. Genetic differences to code the enzymes may result in individual variation to metabolize drugs. Gender difference affects the drug-metabolizing reaction rate. Thyroid, pituitary, and growth hormones affect the development and pattern of drug metabolism. In addition, physiochemical nature of drug, disease state, and pharmacokinetic factors may also modify the metabolizing pattern and capability. This chapter provides an insight on development and mechanisms of various physiological factors affecting DMEs.