The in vivo evaluation of the effect of age and sex on the developmental profile of aminopyrine N-demethylase activity in the newborn rat.

Standard methods for studying the maturation of the hepatic monooxygenase system in neonatal rats require killing groups of animals at various ages. We have developed a simple noninvasive technique which can be used in serial studies on a single animal over a period of time and which accurately reflects changes in hepatic aminopyrine (AP) N-demethylase activity. Rats between the ages of 2 hr and 21 days were injected ip with 4-(N,N-di[14C]methyl)aminoantipyrine and the expired 14CO2 was continuously collected over a period of 3 hr. The peak rate of expired 14CO2 ranged from 0.0054% of the dose per min in 2-hr-old neonates to 0.28% of the dose per min in 21-day-old rats. In order to validate the AP CO2 breath test (ABT), individual mean rates of expired 14CO2 at 25 min and hepatic 9000g supernatant AP N-demethylase activity were compared in the developing neonate between the ages of 2 hr and 21 days. the correlation between changes in mean rate in vivo (as determined by the ABT) and 9000g supernatant AP N-demethylase activity per liver throughout development was excellent (r2 = 0.94). Finally, differences in the ABT of male and female rats were found to reflect expected changes in hepatic AP N-demethylase activity in vitro.