Evaluation of mannitol, lactulose and 51Cr-labelled ethylenediaminetetra-acetate as markers of intestinal permeability in man

1. Factors affecting the intestinal uptake and urinary excretion of mannitol, lactulose and 51Cr-labelled ethylenediaminetetra-acetate (51Cr-EDTA), have been investigated in normal subjects and three patients with ileostomy. 2. The distribution volume of markers within the body, the rate of disappearance from plasma and renal clearance were assessed after an intravenous injection of a mixture of mannitol (2 g), [14C]mannitol (10 μCi), lactulose (0.1 g) and 51Cr-EDTA (5 μCi). 3. The urinary recovery of all the intravenously administered markers was close to 100%. Distribution volumes and patterns of excretion were virtually identical. Oxidation of intravenously administered mannitol accounted for only about 1% of the dose. 4. The passage of an orally administered mixture of markers was traced through the intestine and into urine. Transit time through the gastrointestinal tract was measured by the breath hydrogen method and by radionuclide scanning. 5. The passage of markers from mouth to the large bowel was essentially complete by 3.5 h. In some subjects the marker appeared in the large bowel as early as 30–40 min but in others it took three times as long. 6. After an oral dose the urinary excretion of mannitol fell progressively from 2 to 6 h, whereas the excretion of lactulose and 51Cr-EDTA increased slightly. As a consequence the lactulose/mannitol and 51Cr-EDTA/mannitol ratios in urine collected between 0 and 2 h were more than twofold higher than in urine collected between 4 and 6 h (P < 0.001). After 6 h, the urinary excretion of mannitol and lactulose declined rapidly in all subjects, and was similar to the pattern of excretion of 51Cr-EDTA in subjects with an ileostomy. In contrast, in normal subjects, the excretion of 51Cr-EDTA did not decline rapidly but continued for 24–48 h. 7. Differences in the excretion of mannitol, lactulose and 51Cr-EDTA after oral dosing is due to differences in the temporal pattern of absorption of these markers and not to differences in their distribution volume, oxidation or their clearance by the kidney. 8. The data suggest that the uptake of lactulose by the small intestine persists for longer than the uptake of mannitol, and show that 51Cr-EDTA is readily absorbed in the colon. This study indicates factors which must be considered in the design and interpretation of tests of small intestinal permeability.