Hybrid information provided by the 14C-aminopyrine breath test studies with 14C-monomethylaminoantipyrine in the guinea pig

Abstract

N-Demethylation of ¹⁴C-aminopyrine (¹⁴C-AP), labelled at the methyl groups of the tertiary amino group, yields H¹⁴CHO and ¹⁴C-monomethylaminoantipyrine (¹⁴C-MMAAP) which also undergoes N-demethylation, however, at a slower rate as measured in hepatic microsomes. As after intraperitoneal application to male guinea pigs of ¹⁴C-AP (75 mg/kg; 50 μCi/kg), exhalation rate of ¹⁴CO₂ declines in a biphasic manner, the hypothesis was tested whether the terminal part might reflect N-demethylation of MMAAP. The application of ¹⁴C-MMAAP (70 mg/kg; 10 μCi/kg), resulted in monophasic curves of ¹⁴CO₂ exhalation rate. Their half lives were, however, longer than terminal half lives obtained after ¹⁴C-AP. Obviously, this terminal phase does not represent ¹⁴CO₂ formation from the metabolite MMAAP only, but ¹⁴C-AP might still contribute to ¹⁴CO₂ production. Confirmation was obtained by HPLC determination of AP and MMAAP in serum after injection of AP. Shortly after injection, high concentrations of AP and low ones of MMAAP were found in blood from the portal vein and systemic circulation. Thus, initial parts of ¹⁴CO₂-exhalation rate curves reflect predominantly AP metabolism whereas later phases provide hybrid information.