Printed in U. S. A. Use of Metabolite Exhalation Rates as an Index of Enhanced Mixed-function Oxidase Activity in Vivo

The usefulness of determining aminopyrine demethylation kinetics via monitoring of metabolite exhalation rats had been assessed. In rats receiving ( N-dlmethyl-’4C]aminopyrlne, a biexponential decline in the 14C02 exhalation rate is apparent when monitoring is contin-ued over a 5 to 6-hr period. Both the fast phase (representing the first demethylatlon) and the slower phase (representing the second demethylation) are markedly Influenced by phenobarbital and pro-methazine pretreatment. These changes are consistent with en-hanced mixed-function oxidase activity. Examination of the urinary excretion products of aminopyrine obtained in these studies support this claim. The sensitivity of the above index of mixed-function oxidase activity is increased considerably by the use of crossover experimental designs. Considerable lnteranimal variation is ob-served in the metabolite production In both exhaled air and urine from rats administered aminopyrine