Output ofCO in breath after oral administration of (C-methyl) aminopyrine in hepatitis, cirrhosis and hepatic bilharziasis: Its relationship to aminopyrine pharmacokinetics.

The time-course of aminopyrine in plasma and ofCO in breath was determined for 6 hours after oral administration of (C-methyl) aminopyrine to healthy controls and to patients with hepatitis and hepatic fibrosis, cirrhosis and hepatic bilharziasis.CO in breath declined about 1.8 times more slowly than aminopyrine plasma levels, which suggests the occurrence of metabolite demethylation. This was confirmed by the slow elimination ofC from plasma, the formation ofCO after aminopyrine had disappeared and the presence of a considerable amount of monomethyl-aminopyrine in plasma. The meanCO concentration in breath was correlated with but was not proportional to aminopyrine clearance, which was attributed to individual differences in aminopyrine half-life. Both a correlation and proportionality were found whenCO extrapolated to zero time was used as a parameter ofCO production. Hepatic disease affected aminopyrine clearance to a variable extent. In the hepatitis and fibrosis group, aminopyrine clearance was affected in 2 out of five subjects. In all except one cirrhotic subject aminopyrine clearance was markedly decreased. Moreover, in three out of seven cases aminopyrine absorption was impaired, presumably due to decreased gastrointestinal blood-flow. This may produce an erroneously lowCO concentration in breath during the first two hours after aminopyrine administration. Hepatic bilharziasis was accompanied by very low aminopyrine clearance in all four cases. In two patients high apparent V values were observed, probably due to 'first-pass' metabolism. Patients with ascites had V values within normal limits. [ABSTRACT FROM AUTHOR]