Age and Exposure Factors in Drug Metabolism

Abstract

The development of drug metabolism in the foetal and postnatal periods varies in different species. It is also different in different tissues. The capacity of tissues to catalyze drug hydrolysis, oxidation and reduction as well as the conjugation reactions appears to mature in different phases. The human foetus seems to be better equipped than the foetuses of other species, since both drug hydroxylation and e.g. salicyluric acid synthesis take place sooner than in other species. Glucuronide synthesis can also be detected early in human foetal tissues. During adulthood the drug metabolism decreases with age at least in the rat. The exposure of the organism to foreign compounds often results in an increase in the rate of drug metabolism. This can also be detected in foetal tissues. In the liver similar responses to successive exposures to inducing chemicals can be found at least in the young adult rats, providing they have had sufficient time to recover from previous loadings. In old rats the drug metabolizing enzymes are poorly induced. The diseased state of organs responsible for the detoxication reactions show a lower capacity to handle drugs. The mucosal cells of the intestine serve as a special model for studies on drug biotransformation, since their life span is short and cells at different developmental phases are available at the same time.