A NOVEL STABLE-ISOTOPE BREATH TEST - C-13-LABELED GLYCOSYL UREIDES USED AS NONINVASIVE MARKERS OF INTESTINAL TRANSIT-TIME

Objectives: Breath tests are widely used for diagnosis and control of treatment efficacy. There is a need for breath test substrates that re flect intestinal transit times under various conditions. Methods: We s ynthesized a new class of breath test substrates, C-13-labeled glycosy l ureides, which are specific markers for the action of colonic microb ial flora. We then investigated their usefulness as markers of intesti nal transit time. Results: Bolus ingestion of 1 g lactose or cellobios e C-13-ureide resulted in bacterial cleavage of the N-glycosyl bond an d subsequent urea hydrolysis. (CO2)-C-13 appeared in breath and was de termined by gas-isotope-ratio-mass spectrometry. Label first appeared after 5-6 h, peak excretion occurred between 8-14 h, and the signal re turned to baseline after 18-24 h. Metoclopramide (10 mg) administered 1 h before the substrate advanced the onset of the signal by 2.4 +/- 1 .95 h (mean +/- SD; n = 7;p < 0.05) and the time of peak response by 0 .8 +/- 1.44 h, Loperamide (16 mg) broadened the peak and delayed the t ime of breath signal onset by 1.0 +/- 2.78 h and peak excretion by 4.0 +/- 3.7 h (p < 0.05). Conclusions: The glycosyl ureide breath test re flected intestinal transit time and rapid changes in gastrointestinal motility. This test should be useful in the diagnosis of a variety of gastrointestinal motility disorders and in the development of drugs th at affect gastrointestinal motility.