THE DEVELOPMENT OF N-DEMETHYLASE ACTIVITY MEASURED WITH 13C-AMINOPYRINE BREATH TEST

Abstract

Measurement of specifically labelled CO2 in exspired breath after aminopyrine (AP) demethylation by the hepatic mixed function oxidase system has been shown to be a reliable method for estimation of hepatocellular function. We used the 13C-AP breath test to measure the normal development of the N-demethylase activity and started 13C-methacetin breath test for investigation of O-dealkylation in children. 25 children with normal liver function, aged 2 days to 14 years, received 5 mg/kg body weight AP orally. 13CO2 analysis in breath was performed with a mass spectrometer Varian MAT 230. Results were calculated as cumulative %-recovery of the administered dose. 13C after 2 hours (%-dose), corrected for body weight and endogenous CO2 production.In neonates no 13C excretion could be detected. N-demethylase activity then slowly increased and reached adult levels by 2 years of life.(%-dose = 12.2 ± 2.1). Children with liver disease (%-dose = 4.0 ± 1.3) and treated with antiepileptic drugs (%-dose=16.7 ± 2.5) could be well discriminated. Neonates whose epileptic mother were treated with primidone during pregnancy showed a 13C excretion similar or better than normal adults, thus demonstrating pre- or perinatal inducibility of the N-demethylase activity.