preliminary testing of the prediction that caffeine, a low extraction ration drug (0.1) should be a more sensitive probe of enzyme inducttion than methacetin, a high extraction ration drug (0.9), when excretion of a metabolite (C02) is measured has been carried out. A single dose of each was administered to 8 healthy volunteers and 9 epilepsy patients treated with phenytoin, carbarazepine and/or phenobarbital. The 13C carbon dioxide in expired breath was measured y isotope ratio mass spectrometry. The percentages of the dose excreted as CO2 in 2 hr. were compared: 3.22% + 0.86 and 5.54% + 1.59 caffeine was excreted by controls and patients, respectively, compared with 28.6% + 5.8 and 40.0% + 4.2 methacetin. The results in the 2 subject groups were significantly different for both probes (p<.05). These data do not support the theoretical prediction that the extraction ratio of a drug has a critical effect upon its usefulness in detection of induction of oxidative metabolism via the carbon dioxide breath test. In addition, preliminary data illustrate the potential usefulness of this test to follow the time course of changes in drug metabolism/liver function of an alcoholic patient when he stops drinking.
