VALIDATION OF CAFFEINE/METHACETIN 13C BREATH TESTS

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DESCRIPTION: (Adapted from the Applicant's Abstract). This study will investigate caffeine and methacetin breath tests in normal volunteers and validate the use of the tests for assessing hepatic cytochrome P450-IA2 activity. The effect of charcoal broiled beef and changes in protein/carbohydrate ratio on the hepatic metabolism of these substrates will be examined. The fundamental hypothesis is that these breath tests will accurately estimate hepatic microsomal activity. The long term goal is to validate these tests for use in drug trials. The tests could then be used to determine the amount of hepatic microsomal activity of subjects participating in such trials. It is suggested that knowledge of the effect of dietary and environmental factors on drug metabolism would lead to more accurate determinations about therapeutic dosages for new drugs. Studies are planned using normal healthy subjects to examine the metabolism of 13C-caffeine and 13C-methacetin during controlled dietary periods. Metabolism of the test compounds will be monitored by isotope ratio mass spectrometry.