The enzyme systems in phase I and II reactions are age-dependent. These systems are poorly developed in human newborns because their ability to metabolize any given drug is lower than that of adults. Older adults also have a lower capacity than young adults to metabolize drugs.
Nutritional factors can also affect the enzymes involved in phase I and II reactions. Insufficient protein in the diet to sustain normal growth results in the production of fewer of the enzymes involved in drug metabolism.
It is well known that drug-metabolizing enzymes can be induced by certain factors, such as polycyclic aromatic hydrocarbons. Persons who smoke inhale polycyclic aromatic hydrocarbons, increasing the metabolism of certain drugs, such as caffeine.
The role of genetics in the regulation of drug metabolism by the liver is less well understood. Briefly, drug metabolism by the liver can be controlled by a single gene or several genes (polygenic control). Careful study of the metabolism of a certain drug by the population can provide important clues as to whether its metabolism is under single gene or polygenic control. Genetic variability combined with the induction or inhibition of P450 enzymes by other drugs or compounds can have a profound effect on what is a safe and effective dose of a medicine.
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