The total disposition in man of methacetin, a drug used in the carbon dioxide breath test has been investigated. Plasma and urine concentrations of methacetin and its metabolites, acetaminophen, acetaminophen glucoronide and acetaminophen sulfate were measured by high performance liquid chromatography. The 13C-carbon dioxide in expired breath was measured by isotope ratio mass spectrometry. The fraction of the methacetin dose demthylated was calculated according to clearance concepts and also from measurement of urinary metabolites after a single dose each of methacin and acetaminophen. It was found that 100% of the methacin dose was demethylated to acetaminophen, but only 51% of the methyl carbon atoms were eliminated in breath as carbon dioxide.
