Molecular Pharmacology, Vol 13, 1092-1104, Copyright © 1977 by the American Society for Pharmacology and Experimental Therapeutics

Characteristics of the Liver Microsomal Drug-Metabolizing Enzyme System of Newborn Rats

¹ Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois 60612

Sodium dithionite-reduced hepatic microsomes from neonatal (5-7-day-old) rats displayed (a) an absorption maximum at 452 nm in the presence of carbon monoxide and (b) an equilibrium for the ethyl isocyanide-induced absorption peaks at 430 and 455 nm at pH 7.9. These preparations elicited little or no spectral change with ethylmorphine but elicited the type R-I spectral change with other type I substrates. Carbon monoxide formation in the presence of NADPH and the rate of conversion of cytochrome P-450 to cytochrome P-420 by mersalyl (sodium [(3-hydroxymercuri-2-methoxypropyl)-carbamoyl]phenoxyacetate) were greater in microsomes from neonates than in those from adults. In the presence of NADPH, lipid peroxidatic activity was high, ethylmorphine N-demethylation was low, and aniline hydroxylation was the same in microsomes from neonates compared with the same activities in microsomes from adults. In the presence of NADH, ethylmorphine N-demethylase activities in both the adult and neonatal preparations were identical, but more cytochrome P-450 was reducible by this nucleotide in the latter preparation. These observations demonstrate that the drug-metabolizing system of the neonate differs from that of the adult.