Biotransformation of Drugs and other Xenobiotics during Postnatal development

Abstract

Biotransformation reactions show in dependence on reactio n type, species (strain), organ (tissue) and sex (in rats and mice) developmental patterns with maximum activities in juvenile or young adult animals. Also in man drug disposition in newborns is generally much lower than in children and young adults. Mammals with long gestation periods (guinea pig, rabbit, also man) are born with considerable activities and adult values are reached earlier than in animals with short gestation periods. Highest activities (with very few exceptions) are observed in liver in all postnatal ages. Most of these reactions are inducible by inducers of the phenobarbital-, 3-methylcholanthrene- and tetrachlorodibenzo-p-dioxide, steroid- or alchohol-type. Inducibility also depends on reaction type, species (strain), organ (tissue) and sex (in rats and mice). It begins in the earliest embryonic stage and reaches high rates in species with long gesta- tion periods before birth, and at or after birth in species with short gestation periods. The beginning of high inducibility depends also on inducer type and the induced parameter. Inducible reactions can be increased in immature as well as in very old animals up to or above the level of adult control animals. Isozymes may show different developmental patterns and inducibilities. Development and induction of isozymes or of enzymes catalyzing different reactions can be triggered in clusters. There is increasing evidence that basic biotransformation activities as well as their inducibilities by foreign compounds are essentially influenced by a kind of temporal genetic control during the whole life span.