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 microCi), lactulose (0.1 g) and 51Cr-EDTA (5 microCi). 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 less than 0.001). After 6 h, the urinary excretion