PERINATAL DEVELOPMENT OF DRUG-METABOLIZING ENZYME ACTIVITY IN SWINE

¹ Section of Comparative Pharmacology, College of Veterinary Medicine, University of Missouri, Columbia, Missouri

Three oxidative, one reductive, one hydrolytic and one synthetic mechanism were studied in vitro utilizing preparations of liver and kidney obtained from pigs at weekly intervals from the 100th day of gestation through the 10th week postpartum. The oxidation of hexobarbital, l-amphetamine, p-nitroanisole and zoxazolamine, the hydrolysis of procaine and the glucuronidation of phenolphthalein occurred at very low rates in the tissues of the fetal and newborn pig, whereas the capacity for azo reduction of Neoprontosil by both tissues was evident at these ages. The postnatal pattern of development in liver appeared to be biphasic in nature, with the greatest rate of increase in activity occurring during the first three to four weeks postpartum for all pathways except azo reduction (four to six weeks). The reductive and hydrolytic mechanisms developed slowly in kidney after birth, whereas the capacity of this organ for oxidative metabolism or for glucuronic acid conjugation was insignificant at all ages. The content of glycogen in the liver at various ages after birth did not correlate well with the development of drug-metabolizing enzyme activity over the entire period studied. The CO-binding pigment (cytochrome P-450) of hepatic microsomes developed in parallel with the oxidative and reductive pathways, suggesting that this cytochrome may be rate-limiting to the development of these pathways.