The aminopyrine breath test as a measure of liver function: a quantitative description of its metabolic basis in normal subjects

A dual-isotope kinetic study of aminopyrine disposition and metabolism has been carried out on five normal adult subjects. Oral administration of 13C-aminopyrine (2 mg/kg) accompanied by simultaneous intravenous injection of 14C-aminopyrine was followed by serial measurements of aminopyrine and monomethylaminopyrine in plasma and urine over 6 hr. Timed collections of respiratory CO2 were analyzed for the content of excess 13CO2 and for 14CO2. On separate days, an intravenous bolus of 13C-labeled NaHCO3 was administered to obtain estimates of the kinetic parameters of CO2 elimination in each subject. These data were fitted simultaneously to a multicompartmental model that, in addition to providing hitherto unavailable quantitative information, has revealed that (1) demethylation is the major elimination pathway for aminopyrine; (2) a major alternative pathway not involving demethylation exists for monomethylaminopyrine; and (3) only 50% of the labeled carbon generated by demethylation eventually is oxidized to HCO3-. The sensitivity of seven types of APBT scores to 50% reductions in the rates of aminopyrine absorption, metabolism of monomethylaminoantipyrine, intermediate carbon metabolism, and bicarbonate kinetics was evaluated with breath test curves simulated using the APBT model. Every APBT score currently in use was affected by variations in both gastrointestinal output of aminopyrine and bicarbonate kinetics. There is a need for further development of selective scoring methods in the aminopyrine breath test