Interpretation of CO2 exhalation rate data from demethylation of aminopyrine and its metabolite monomethylaminoantipyrine.

Abstract

1 Aminopyrine breath tests make use of the commercially available (N- dimethyl-[14C])-aminopyrine. A pharmacokinetic model has been proposed to relate 14CO2 exhalation rates (CER) to the demethylation of ([14C]- methyl)-aminopyrine (AP) and -monomethylaminoantipyrine (MAP). 2 computer simulations based on the model show that the shape of the CER- time profile is largely dependent on the ratio of the MAP to AP elimination rate constants. If this ratio equals 0.5 then the CERs decline in the monoexponential fashion. Ratios less than 0.5 result in concave biexponential curves whereas ratios greater than 0.5 result in convex curves. When demethylation is not complete for both compounds the transfer from biexponential to monoexponential behaviour will only occur at ratios greater than 0.5. 3 The resolution of concave biexponential CER-time profiles to give accurate estimates of AP and MAP elimination rate constants can only be achieved when the length of the experiment is adequate. The commonly employed 2 microCi tracer dose of aminopyrine is insufficient to monitor CER over the necessary time period to detect the proposed biexponential decline.