AMINOPYRINE DEMETHYLATION KINETICS - USE OF METABOLITE EXHALATION RATES AS AN INDEX OF ENHANCED MIXED-FUNCTION OXIDASE ACTIVITY INVIVO

  • 1 January 1981
    • journal article
    • research article
    • Vol. 9  (5) , 449-455
Abstract
The usefulness of determining aminopyrine demethylation kinetics by monitoring metabolite exhalation rates was assessed. In rat receiving [N-dimethyl-14C]aminopyrine, a biexponential decline in the 14CO2 exhalation rate is apparent when monitoring is continued over a 5- to 6-h period. Both the fast phase (representing the 1st demethylation) and the slower phase (representing the 2nd demethylation) are markedly influenced by phenobarbital and promethazine pretreatment. These changes are consistent with enhanced mixed-function oxidase activity. Examination of the urinary excretion products of aminopyrine obtained 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 interanimal variation is observed in the metabolite production in both exhaled air and urine from rats administered aminopyrine.