which compounds that are normally excluded by the gastrointestinal tract of children and adults are absorbed.
Age-Related Changes in Absorption. Although there is a paucity of data on absorption of drugs as related to age in human neonates and infants, some definitive investigations have been conducted using laboratory animals. Hoffmann (1982) summarized the results of a number of animal studies. The rate of penetration of four model compounds (antipyrine, sodium salicylate, tetraethylammonium bromide, and phenosulfonphthaline) from everted intestinal sacs of rats was evaluated in an in vitro experiment. Penetration of all compounds was two to three times greater for 10- than for 30-day-oldrats, which in turn exhibited somewhat greater penetration rates than did adult animals. In an in vivo study, disappearance of the compounds from the duodenum of anesthetized rats was examined. Antipyrine, sodium salicylate, and tetraethylammonium bromide were each absorbed more rapidly by 10-day-old rats than by adult rats. These differences in the rate of absorption were not reflected by differences in blood levels, apparently because of a greater volume of distribution in the neonatal rats. Large synthetic molecules such as polyvinylpyrrolidinone have also been found to be well absorbed in neonatal and suckling mammals, as have heavy metals (Hoffmann, 1982). Closure, or decrease to the low-level uptake characteristic of adult animals, generally has been found to occur at the time of weaning.
Closure has been associated with structural and functional maturation of intestinal epithelial cells. It has been suggested that a marked reduction in pinocytotic activity is largely responsible for this phenomenon. Pinocytosis is believed to be the primary mechanism for nonselective absorption of macromolecules by the neonatal intestinal epithelium in mammals (Lecce, 1972). Bierring et al. (1964) observed large numbers of pinocytotic vacuoles associated with phagosomes at the base of microvilli in the intestinal epithelial cells of human fetuses. Udall and Walker (1982) saw such vacuoles associated with an extensive apical tubular network system, as well as pseudopodlike cytoplasmic extensions projecting through the lamina propria in the intestine of 1-week-old rabbits. The intestinal epithelium of the adult rabbit showed a marked decrease in the tubular network and pseudopods, which accompanied cessation of systemic uptake of bovine serum albumin. Pang et al. (1983) found that the membrane of newborn rabbits had a significantly higher lipid-to-protein ratio than did that of adult animals. Electron spin resonance spectra revealed that the membranes from the newborn rabbits were more disorganized and fluid, which could account for the more efficient penetration and diffusion of macromolecules during the perinatal period.
Absorption and Retention of Lead and Other Heavy Metals Although